Final Report

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Chapter 7

An Investigation into the Deaths of the Reverend David Black, Mrs Eileen O'Hara, Mr Alexander Black Laing and Mr Victor Tamburrini


7.1 The matters which the Inquiry was asked to investigate and report upon were set out in the Terms of Reference issued up by the Cabinet Secretary for Health and Wellbeing, following consultation. Term of Reference 6 required the investigation of the deaths of certain named individuals with particular reference to the circumstances in which they became infected with Hepatitis C, HIV or both. In the event, none had acquired infection with HIV.

Term of Reference 6.

To investigate the deaths of Reverend David Black, Mrs Eileen O'Hara, Alexander Black Laing and Victor Tamburrini, with particular reference to the circumstances in which they became infected with the Hepatitis C virus, HIV or both.

7.2 Originally, the Inquiry was required to investigate the deaths of Reverend Black and Mrs O' Hara only. Those particular deaths were selected as the personal representatives of the two deceased had raised proceedings in the Court of Session to challenge decisions made by the Lord Advocate and the Scottish Ministers, respectively, not to investigate the circumstances of those deaths. In February 2008 the Court of Session quashed the Lord Advocate's decision. The Scottish Ministers' decision was not then quashed having regard, amongst other things, to the fact that on 16 June 2007 the Scottish Government had re-affirmed its commitment to hold 'a general Public Inquiry' to 'find out why people were infected with Hepatitis C through NHS treatment'. Upholding that commitment, on 23 April 2008 the Scottish Ministers set up this Inquiry under the Inquiries Act 2005. On 13 November 2009, the Scottish Ministers added three further deaths for investigation: Mr Laing, Mr Tamburrini and Mr Neil Mullen. On 22 February 2011, however, at the request of his family, Mr Mullen's name was removed from the list of deaths to be investigated. As noted above, none of the individuals whose deaths the inquiry was asked to investigate was infected with HIV.

7.3 As the personal representatives of the deceased were expected to have a key role during the Inquiry, they applied for and were designated as Core Participants. In addition, they were awarded funding for their legal representation, which was provided through Thompsons, Solicitors. The four personal representative Core Participants were:

  • Mrs Jean Black as the personal representative of the Reverend Black.
  • Mrs Roseleen Kennedy as the personal representative of Mrs O'Hara.
  • Mrs Annie Laing as the personal representative of Mr Laing.
  • Mrs Jean Tamburrini as the personal representative of Mr Tamburrini.

7.4 An important early step in the investigation process was the obtaining of the medical records of the deceased. Principals were obtained where they existed. Records were recovered from the relevant Health Boards and the Crown Office and Procurator Fiscal Service. Documents were also recovered from the Scottish National Blood Transfusion Service (SNBTS).

7.5 Suitable medical experts were identified and instructed to provide independent, expert reports in order to help focus the issues for investigation into each of the deaths. The expert reports were circulated for observation and comment to the legal representatives of all the Core Participants which, in addition to the personal representatives, included Haemophilia Scotland, the Scottish Ministers, the SNBTS,[1] the 14 Scottish Area Health Boards and 15 individuals as representative of classes of patient interests.

7.6 Written statements were taken from the personal representatives of the deceased and other individuals.

7.7 The public hearings began with the taking of detailed evidence relating to each of the deaths. This approach was adopted in order to ensure that any issues which arose in the course of those investigations and which had significance beyond the individual death under consideration could be noted and explored subsequently in the course of the topic- based investigations. Accordingly, information obtained as a result of the intense scrutiny to which each death was subjected assisted in understanding important systemic issues which were of relevance in the later consideration of many of the additional terms of reference. Evidence on the deaths was heard over four days, from 8-11 March 2011 and 12 witnesses appeared in order to assist the Inquiry in this matter.

7.8 Immediately following the conclusion of this evidence, a public session was held at which Senior Counsel for the Inquiry and Counsel representing the Core Participants sought to identify systemic issues arising from the evidence. In the event, no issues additional to those already scheduled to be covered in hearings arose from evidence in relation to the specific deaths.

7.9 Before the conclusion of the Oral Hearings phase of the Inquiry, all Core Participants' legal representatives were invited to make written submissions on what they considered to be the questions and issues arising from the evidence. They were also permitted to comment upon the written submissions of other Core Participants.

7.10 The personal representatives of the deceased, Haemophilia Scotland and the patient interest Core Participants, who were all legally represented by Thompsons, Solicitors, jointly made written submissions in relation to the deaths. The SNBTS and the Health Boards, jointly represented by the Central Legal Office of the Common Services Agency, provided comments in relation to the submissions on the Reverend Black and Mr Laing.

7.11 Having considered all the evidence before the Inquiry, this chapter sets out the Inquiry's findings in relation to each of the deaths.

Reverend David Black

7.12 Mr Black was born on 1 May 1937. He died on 31 October 2003 at Strathcarron Hospice, Stirlingshire. The cause of death was registered as hepatocellular cancer in a transplanted liver, Hepatitis C, transfusion of blood products and haemophilia.[2]

Mr Black's early medical history in relation to haemophilia

7.13 There was a history of haemophilia in Mr Black's family.[3] He was diagnosed as having the disease in the early 1940s when he was five.[4] A possible alternative diagnosis of von Willebrand's disease[5] was considered in the early 1970s.[6] However, his von Willebrand Factor antigen was 65% of normal, the relevant bleeding time test was normal and the correct diagnosis was almost certainly Haemophilia A.[7] When his condition was investigated, it was found that he had a resting Factor VIII level of between three and seven international units per decilitre (3-7%).[8] Along with his history of treatment, that was consistent with mild to moderate Haemophilia A.[9] For the purposes of this Report, that diagnosis is accepted.

7.14 Mr Black's early medical history was typical of a child with relatively mild haemophilia. He did not have haemarthrosis (bleeding into his joints) or spontaneous bleeding. He required occasional treatment with blood, blood components and blood products in response to specific events, however. Mr Black was probably first treated aged five when he had a haemorrhage; thereafter, on his own account, he was given 'transfusions', mainly for procedures such as tooth extractions from time-to-time.[10] His early records were incomplete: it was recorded that he had been given blood or plasma once at Edinburgh Sick Children's Hospital and twice at Glasgow Western Infirmary.[11] In October 1965, it was recorded that he had received plasma once at the Glasgow Royal Infirmary (GRI), in 1957, when he had a sudden episode of haematuria (blood in the urine).[12] He was treated at various times at Professor Alexander Douglas' clinic and by Dr Paul Davis, Dr Colin Prentice and Professor Gordon Lowe (who would become Co-Director of the Glasgow Hemophilia Centre in 1988).

7.15 More detailed records were available from the 1960s and Mrs Black was able to supplement these from her own recollection. Mr and Mrs Black met in 1961.[13] Mrs Black had been a nurse and was more familiar than some with the diseases and terminology relevant to the Inquiry.[14] The account of Mr Black's medical history reflects her evidence in addition to evidence drawn from Mr Black's medical records. Mrs Black was rather frail at the date of the Inquiry's Oral Hearings. So far as her positive recollections are concerned, her written witness statement is accepted as generally true and reliable. Not surprisingly, there are omissions from her account and some of these at least were made good by the medical records.

7.16 Mr Black was admitted to the GRI on 20 October 1965, then aged 28, for a tooth extraction. He was given four flasks of antihaemophilic globulin (AHG), an early form of NHS Factor VIII concentrate prepared in Edinburgh.[15] AHG was a crude plasma product and Mr Black was given phenergan and cortisone, probably to reduce or eliminate the risk of an allergic reaction to the treatment. In the event, the extraction was without difficulty and bleeding was not troublesome.[16]

7.17 The next recorded hospital visit was in May 1969 when he again required dental treatment.[17] On this occasion he was probably treated with cryoprecipitate, a frozen plasma product derived from a single donor's blood. AHG was by this point in short supply; by that date, treatment with cryoprecipitate was in general use throughout the UK.[18]

7.18 Mr Black also received treatment abroad. Though specific instances are recorded, there is inevitably a lack of certainty about his history of treatment in other countries. He was a Baptist minister and worked both in the USA and in developing countries. At one point he worked for Oxfam. After their marriage, he, Mrs Black and their family travelled widely. Inevitably, there is a risk that his Scottish medical records do not reflect all of the treatment he received and some of his known history depends solely on Mrs Black's recollection.[19]

7.19 Mrs Black said that her husband received blood products in San Jose, California, in 1970 when treated for a kidney stone.[20] He was working in South Korea at the time and was treated en route to or from there.[21] At this time, US pharmaceutical companies were in the vanguard in developing large-pool concentrates (concentrates, that is, prepared from a large number of donations from a large number of donors). Clinicians there were ahead of UK doctors in the use of concentrates: Dr Brian Colvin[22] said that he and his colleagues at the London Hospital were just beginning to use them in 1970. He thought that it was entirely possible that treatment received by Mr Black in the USA in 1970 would have involved an American large-pool concentrate.[23] A positive finding to that effect cannot be made, however, as cryoprecipitate continued to be the therapeutic material of choice for some clinicians at this time. Mr Black was treated by Dr Judith Pool in Stanford Medical Centre.[24] Dr Pool, noted by Dr Colvin as the 'founding mother' of modern haemophilia care, described the preparation of cryoprecipitate in 1964 and 1965[25] and reported use of that product in 1966.[26] It is not unlikely that she would have continued to use cryoprecipitate, the product she had devised and developed, even though early forms of large-pool concentrates were becoming available. It is not possible to resolve the issue of which product she may have used to treat Mr Black in 1970.

7.20 For a period after 1970, Mr Black had no treatment in the UK. He was referred to the GRI following his treatment in the USA[27] and had tests in April and May 1971.[28] In April, he reported no haemostatic problems and the examination disclosed no other problems at that time apart from some slight tenderness over the left renal angle (the area of the lower back around the site of the kidney).[29] In May, he was seen by Dr J F Davidson, who reported that Mr Black was still complaining of vague ill-health, with an ache in his right lumbar region, and that they could find no cause for his backache.[30] On 7 February 1973, the Regional Haemophilia Centre wrote to him asking him to attend in order to bring his records up to date, as he had not been reviewed at the Centre for four years.[31] In February 1974 he had chest pains and was referred to the GRI.[32] In May 1974, he reported that he had been keeping fairly well and had not had bleeding problems, although he again expected to need dental treatment.[33] Mr Black appears to have changed GPs about mid-January 1975. A letter dated 17 January 1975 was sent to his new GP informing him of the Haemophilia Centre's interest. The letter commented that Mr Black did not appear to have any problems except when faced with a haemostatic challenge (such as trauma, surgery and dental extractions); when that occurred, he would require active Factor VIII replacement therapy.[34] That was consistent with his recorded history up to that point.

7.21 On 26 and 27 June 1975, Mr Black attended the GRI with pain in his left knee. On clinical examination this was thought to relate to a haematoma (subcutaneous clotted or partially clotted blood) rather than a haemarthrosis. He had factor replacement therapy at that stage, probably with large-pool concentrate.[35] In May 1978 he required SNBTS Factor VIII concentrate and cryoprecipitate to support a tooth extraction.[36] In February 1979, Mr Black again had cryoprecipitate prior to a dental extraction and, on this occasion, also to deal with post-extraction bleeding.[37]

Evidence of Hepatitis C infection

7.22 Mr Black was reviewed in the autumn of 1976[38] and in the spring of 1978.[39] He did not report any bleeding problems but on the second visit complained of chest and abdominal pains. Tests were negative for abnormalities of the oesophagus, stomach and duodenum (the first section of the small intestine) and there was no evidence of a peptic ulcer.[40] In September 1978, his condition was unchanged and he reported no new problems.[41] There were no recorded signs of hepatitis infection at that time, although, in retrospect, his blood test results can be associated with Hepatitis C infection.

7.23 On 14 December 1979, elevated liver function test results were recorded for the first time when his transaminase GOT[42] was 97.[43] The majority of his liver function test results after this date were abnormal.[44] As the natural history of the disease is now understood, this was typical of Hepatitis C infection, then covered by the umbrella term 'non-A non-B Hepatitis' (NANB Hepatitis). There were few diagnoses of NANB Hepatitis in Scotland before the late 1980s.[45] In Mr Black's case, however, it was recognised by 1985 that he had NANB Hepatitis, for which no treatment was then available.[46] There was also evidence of previous exposure to Hepatitis B but not of ongoing infection.[47]

7.24 Mr Black had a bleed into the tibial muscles of his right leg in about April 1981. On review on 9 April 1981, the last previous episode reported was of bleeding into the renal tract while in America.[48] When he was seen for routine review in September 1984, there was mild crepitus (a 'crackling' sound) in his right knee, suggestive of some underlying arthritis. He also complained of occasional lower back pain. Clinical examination was not remarkable and his liver function tests were normal.[49] In December 1985, liver function test results were again significantly elevated.[50] Dr Colvin thought that it was difficult to make much of the increase, however, as fluctuating transaminase results are typical of NANB Hepatitis/Hepatitis C. Inflammation of the liver varies from time to time and it was necessary to look at a sequence of results to tell whether the patient truly had an increase in transaminases.[51]

7.25 In 1987, Mr Black was in Fort Pierce, Florida. He was admitted to hospital there on 30 September complaining of black stools, generalised weakness and lethargy. He was given packed red cell support and cryoprecipitate. He had a Computerised Tomography (CT) scan which proved to be negative for retroperitoneal haematoma or any other intra-abdominal pathology.[52] Upper endoscopy revealed Grade 1 oesophageal varices.[53] This was the first significant episode of clinically apparent liver disease. Liver damage causes a build-up of pressure in the portal venous system which backs up into the stomach and oesophagus and causes internal varicose veins (oesophageal varices) to develop.[54] Though not specifically related to Hepatitis C, in that the condition can have other causes, oesophageal varices associated with liver damage are a frequent complication of cirrhosis.[55] The doctors in Fort Pierce apparently suggested to Mr Black that there was an underlying cause of the varices and that his liver damage was potentially virus-related.[56]

7.26 On return to Scotland, Mr Black was admitted to the GRI in October 1987, where he gave an account of his experience in the USA. On examination, the US findings of varices were confirmed. Mr Black had an old Mallory-Weiss tear (scarring at the gastro-oesophageal junction), a condition usually associated with vomiting.[57] By 1987, the liver and spleen were palpable (noticeable to the touch in examination) and there was evidence of chronic liver disease.[58] Mr Black was informed that the virus could have caused his diseased liver to become cirrhosed.[59] Portal hypertension and the oesophageal varices were treated in a conventional way.[60] Injection sclerotherapy (injection of a hardening solution) was performed on the varices.[61]

7.27 As noted in paragraph 17.23 above, the biochemical abnormalities found in December 1979 were typical of NANB Hepatitis/Hepatitis C infection. By 1987, Mr Black's condition had progressed: there were Grade 1 oesophageal varices, the liver and spleen were palpable and there was portal hypertension. Dr David Mutimer, Consultant Hepatologist, Queen Elizabeth Hospital, Birmingham, considered that it could be assumed that cirrhosis was present in 1987. Since Hepatitis C typically takes at least two decades to develop in a person infected when young, infection had probably been acquired by Mr Black in the 1960s.[62] Dr Mutimer's evidence is accepted.[63] Since his evidence was that it takes 'at least' two decades for the disease to develop, however, the beginning of the period within which transmission occurred remains uncertain.

Source of infection

7.28 No specific source of infection has been clearly demonstrated. In Dr Mutimer's experience, Mr Black's history was fairly typical of patients with haemophilia who acquired Hepatitis C at a fairly young age. After a long duration of infection, he developed severe liver damage with cirrhosis and portal hypertension.[64] Rates of progression to cirrhosis, decompensated cirrhosis, hepatocellular cancer and liver-related death are closely related to age at infection.[65]

7.29 Since there were abnormal liver test results by 1979, and since cirrhosis was established by 1987, it is unlikely, but not impossible, that Mr Black was infected in the USA in 1970. He was then about 33 and at the lower end of the cohort of male patients at the highest risk of developing cirrhosis within 30 years.[66] Having regard to Dr Mutimer's evidence about the natural history of Hepatitis C, the period between 1970 and 1987 was probably too short to provide a reliable basis to infer that the infection was transmitted at this time. On the other hand, some 10% of patients do develop cirrhosis in 15 to 20 years and the possibility of infection in 1970 cannot be wholly excluded. Dr Mutimer's evidence more confidently excludes from responsibility for Mr Black's infection the use of Factor VIII concentrate in 1975 and 1978 and the use of cryoprecipitate in 1978 and later.

7.30 There are three remaining possibilities: the use of blood and plasma up to the late 1950s, the single known infusion of AHG in 1965 and the cumulative use of cryoprecipitate up to the late 1960s. At the material time, AHG was prepared in Edinburgh from plasma pooled from small numbers of donors, limited by the processing capacity of the equipment available at the Royal Infirmary of Edinburgh (RIE). In 1965 the prevalence of Hepatitis C in the blood donor population is likely to have been relatively low and, statistically, the chances of an individual batch of AHG being infected were very low. In the absence of specific evidence it would be impossible to find positively that this procedure was the cause of Mr Black's infection. It might have transmitted infection, however: blood, plasma, AHG and cryoprecipitate were all capable of transmitting infection.

7.31 There was discussion of whether the continued use of cryoprecipitate in Mr Black's therapy in the period 1987-88 was appropriate.[67] Dr Colvin's evidence was that, at that time, to counter the risk of transmission of HIV, effective virus inactivation of factor concentrates had led to a change in recommended practice from the use of cryoprecipitate to the use of heat-treated concentrates. In 1986, when a test for HIV infection had become available, Mr Black had been tested and proved negative.[68] Dr Colvin's view was that, since Mr Black's liver function tests were already abnormal by the mid-1980s and Mr Black was HIV-negative, the use of cryoprecipitate after the introduction of virally inactivated large pool concentrates in the mid-1980s was clinically irrelevant to his case. That view is accepted.

7.32 So far as is material, Dr Colvin thought that Mr Black had probably had enough single donor unit products to expose him to a high risk of having already contracted Hepatitis C before he was first treated with a large pool concentrate around 1975.[69]

7.33 Dr Mutimer reviewed Mr Black's medical records. In his view, exposure to Hepatitis C was almost inevitable as a consequence of the treatment he received for haemophilia.[70] His view was similar to Dr Colvin's.[71] Mr Black had been treated with doses of single donor cryoprecipitate and with Factor VIII concentrate. The more bags or bottles of cryoprecipitate a patient received on a random basis, the greater the chance was that eventually the patient would receive a dose that was infected with Hepatitis C. Every time the patient was treated the risks were the same and, eventually, an infected unit would be transfused.

7.34 In conclusion, Mr Black contracted Hepatitis C from infected blood products. For all practical purposes, infection with Hepatitis C was inevitable given the requirements of haemophilia therapy. Given the wide range of possible durations implicit in Dr Mutimer's evidence about the natural history of the disease, it is not now possible to be specific as to the source of infection. On balance, and on the evidence available to the Inquiry, the most likely source was therapeutic blood products administered in Scotland. It is highly likely that Mr Black was infected by NHS cryoprecipitate or concentrates, probably in the 1960s.[72]

Progress of infection

7.35 Mr Black was due to visit Kenya and Uganda in February 1986. He had a series of tests in advance and it was noted that his transaminases were markedly elevated at that time.[73] In November 1986 and August 1987 he had further dental treatment supported by cryoprecipitate.[74] On each occasion further treatment was required for post-extraction bleeding.

7.36 At about this time Mr Black's health began to take a turn for the worse. As noted in paragraph 7.25 above, he was admitted to hospital in the USA on 30 September 1987. Beginning on 14 October 1987, after his return to Scotland, he had frequent and substantial cryoprecipitate therapy for gastro-intestinal bleeding.[75] In March 1988, he was treated with SNBTS Factor VIII concentrate.[76] Home treatment with SNBTS Factor VIII was prescribed from January 1990 and amounted to 24,850 units in the course of the year.[77] Home treatment continued into 1991. By September 1991, the presumption of his clinicians was that Mr Black's varices were secondary to Hepatitis C as a consequence of the blood products he had received over the years for haemophilia.[78] On 14 October 1991, Mr Black was found to be positive for the antibody to Hepatitis C and that was confirmed by the RIBA-2 test.[79] In August 1992, Monoclate, a commercial Factor VIII product, was prescribed.[80] In 1993, he received further commercial concentrate, HP Factor VIII.[81] Mr Black was now being treated more frequently with factor concentrates.

7.37 In March 1994 a referral was made for consideration of Interferon therapy for the treatment of Hepatitis C. There was extensive discussion and the consultant gastroenterologist, Dr J F MacKenzie, advised that therapy should be tried.[82] Dr Colvin thought it unlikely that treatment would have been effective, however.[83] Dr Mutimer agreed: Mr Black had already developed cirrhosis with evidence of decompensation. Interferon was the only therapy available and was unlikely to help under those circumstances. In retrospect, in all probability, had antiviral therapy been given, it 'would have caused significant morbidity and was unlikely to cure the infection'.[84] Therapy was not started, partly because Mr Black was reluctant to undergo treatment.[85] This was an early indication of Mr Black's attitude to therapy which he was to repeat in response to advice from time to time thereafter.

7.38 In late spring 1994, Mr Black was again in the USA. While there, he developed gross ascites and pitting oedema (abnormal accumulations of fluid in body cavities), both due to salt and water retention and attributable to liver failure.[86] When back in Glasgow, he was told that he would not be well enough to travel to Italy two weeks' from then as he had intended.[87]

7.39 On 6 April 1995, Dr MacKenzie reported to Professor Lowe that there had been a very slow deterioration in liver function and that Mr Black remained 'unkeen' on any medication. Dr MacKenzie suggested that a liver transplant might become an option within the next few years.[88] In May 1995, Dr MacKenzie raised the subject of transplant with Mr Black again. Following discussion, he referred the question whether early- or medium-term transplant would be appropriate, to Dr Alastair MacGilchrist at the Liver Transplant Unit (LTU), RIE, in a letter dated 22 May. Mr Black had indicated that he wanted to discuss the matter with Dr MacGilchrist.[89]

7.40 Dr MacGilchrist saw Mr Black and reported to Dr MacKenzie on 3 July 1995. His assessment was:

Reverend Black is a good candidate for liver transplantation. Clearly, it will be a major undertaking for the blood transfusion service to supply sufficient quantities of Factor 8 to cover the procedure, but this should not be a major problem and ... transplantation has been undertaken successfully with patients with haemophilia elsewhere.[90]

7.41 Mr Black returned to the LTU in September 1995 and was seen by a registrar. He had been researching his condition on his own initiative but was finding it difficult to obtain statistics regarding haemophilia patients who had been transplanted. He was reported to be 'anxious and giving rather mixed messages'. The registrar's view was that he was 'terrified' that his condition was going to deteriorate suddenly to the extent that it would preclude transplantation. She had tried to emphasise to him that that was not the natural course of events and proposed that he should come in for assessment.[91] He agreed and in October/November an assessment was carried out over four days.[92] After comprehensive review by a multidisciplinary team, it was decided that his current liver function and quality of life were such that he did not require liver transplantation at that stage.[93]

The transplant and progression of disease

7.42 In 1996, Mr Black's liver function had deteriorated to the point at which transplantation was considered appropriate.[94] Arrangements were made for him to be admitted for assessment on 18 March.[95] A liver transplant was performed on 21 April 1996[96] and Mr Black was in hospital from 20 April until 13 May. After the operation there was some fluid retention and he was prescribed antibiotics for spontaneous bacterial peritonitis but, by the time of discharge, he looked well with no symptomatic pallor, jaundice or leg swelling. He was to be reviewed in May.[97] The family was encouraged to be optimistic. Mrs Black told the Inquiry, 'The projections at this time were that his new liver would last his lifetime before the Hepatitis C had the chance to affect it.'[98]

7.43 One potentially important finding was made at this time. Mr Black's own explanted liver was sent for detailed pathological examination following the transplantation procedure where it was discovered that his cirrhosis had been complicated by the development of primary hepatocellular cancer.[99] The extent to which that information influenced, or did not influence, his medical care over the following period became the subject of investigation at a later stage and is referred to in paragraph 7.55 onwards below.

7.44 After surgery in April 1996, Mr Black continued to be monitored. When he was reviewed on 24 October 1996 there was a discussion of his long-term prospects. The report from a registrar in the LTU to his GP noted that Mr Black was obviously quite an anxious man. He had enquired about the long-term impact of Hepatitis C recurrence and the chances of developing cirrhosis. He was advised that the long-term prognosis was hard to predict, although it was reasonable to predict that his quality of life should be fairly good for the next 10 years.[100]

7.45 Monitoring continued over the period from 1996 to 2002 and there were frequent discussions about the possibility of drug therapy for his ongoing Hepatitis C when Mr Black attended hospital. He remained uncertain, however. Dr MacGilchrist saw him on 11 December 1997. At that time he was keeping extremely well and working as hard as ever but his liver function tests were causing some concern. Those test results never returned completely to normal and, in particular, his ALT was quite significantly raised. Dr MacGilchrist thought that the results were most likely to represent recurrent hepatitis in his new liver. In order to avoid worrying him over the Christmas period, Mr Black was told only that his liver tests were slightly abnormal and that he should have a repeat test done by his GP in January 1998.[101]

7.46 Mr Black was reviewed during 1998. In April, he was doing well and his liver function test results were slightly better.[102] In November 1998, however, his liver function test results were again causing concern.[103] When Mr Black was seen at the LTU in February 1999, matters had developed further. The report of the review to his GP stated:

He was informed that his liver biopsy showed recurrence of hepatitis C and that we would probably consider treating him for hepatitis C. He himself was not quite sure if that would be the best option for him at this present time as he felt that the side effects of Interferon would be too much for him. He agreed though to have an appointment with our hepatitis C team which will help discuss the options with him.[104]

7.47 The review process continued in and after 1999. In June 1999 combination treatment with Interferon and Ribavirin was discussed with him but he remained rather reluctant to start it.[105] That continued to be his position for a period thereafter.

7.48 In February 2001, Mr Black had a liver biopsy for further assessment of his Hepatitis C. Although he had earlier declined anti-viral therapy, consideration was again given to its commencement.[106]

7.49 In April 2001, Dr Kenneth Simpson, LTU, had a long discussion with Mr Black about treatment. He commented in a letter to his GP that, with the introduction of combination Interferon and Ribavirin, treatment had improved and that Mr Black seemed much more receptive to the idea and had agreed to think about receiving treatment.[107] When he attended for review on 27 September 2001, Mr Black felt that he would be happier to wait before undertaking this therapy in view of the potential side-effects which he might find disruptive to his life. He was very busy at work.[108] Mr Black remained uncertain and Dr Mutimer thought that there was probably uncertainty on the side of the physicians as well: they were aware that the treatment was associated with significant side-effects and that the chances of success were fairly low. He thought that the decision Mr Black took to decline treatment was quite understandable.[109]

7.50 In early 2002, Mr Black's liver function test results continued to show elevated ALT levels.[110] His work commitments were heavy, however, and a decision to start treatment was again deferred. In April 2002 Mr Black had an ultrasound scan with satisfactory results.[111] Liver biopsy revealed Hepatitis C virus fibrosis in the transplanted liver, short of cirrhosis but thought to be more advanced compared to the year before.[112]

7.51 When seen in April 2002, Mr Black said that he might be more amenable to treatment as he was reducing his workload.[113] By that stage he had been told of dual therapy and the improved prospects of success it offered. He was seen by Dr Simpson on 8 August 2002. The diagnosis recorded in a letter to his GP and copied to other clinicians listed the transplant, previous haemophilia and recurrent Hepatitis C with significant fibrosis on liver biopsy.[114] On this occasion Mrs Black was at the review. The letter stated:

I had a long chat with Rev Black about the possibility of treatment, the conversation I had had with him previously. Certainly his liver biopsies have clearly demonstrated progressive fibrosis, and without attempting anti-viral treatment it is clear that he will develop recurrent cirrhosis. He again seemed quite keen in the clinic to start anti-viral treatment ....[115]

7.52 In December 2002, Mr Black commenced treatment with pegylated Interferon and Ribavirin.[116] By then fibrosis was more advanced. The anti-viral treatment did not run smoothly.[117] He experienced anaemia severe enough to necessitate a transfusion.[118] The treatment was abandoned.[119]

7.53 Dr Mutimer said:

The problem with the anaemia is due to the ribavirin component of his treatment, and the main problem is that the dose needs to be adjusted very carefully and frequently in patients if they have any degree of kidney dysfunction, which is quite common in the transplant patient. So I suspect the severe anaemia was because the level of the ribavirin was too high for the patient. But there are no useful published guidelines on picking the right dose.[120]

7.54 In May 2003, Mr Black was admitted for ultrasound-guided liver biopsy. Scans had suggested a possible focal lesion. Two cores of tissue were taken and pathology confirmed hepatocellular carcinoma.[121] Dr Andrew Bathgate, by then a consultant physician at the LTU, told Mr Black that this had happened, and that it was clear from the imaging that the cancer was multifocal.[122] The cancer had spread, probably with multiple nodules throughout the liver.[123] It could not be treated.[124] Mr Black died on 31 October 2003.[125]

Hepatocellular cancer in the explanted liver: Mr Black's management as a patient

7.55 As noted in paragraph 7.43, Mr Black's pathology records revealed that the liver removed at the time of the transplant in 1996 was cancerous. Mrs Black said that it had come as a shock to the family to learn that Mr Black's own liver had been affected by cancer. She said that Mr Black was not aware of that fact and that the family was not aware either. Having regard to the evidence as a whole, including the retrospective investigations carried out by Dr MacGilchrist and comment by Dr Bathgate, it is clear that Mr Black was not told of the hepatocellular cancer in the explanted liver. The discharge letter sent to Mr Black's GP made no mention of any tumours.[126] Consequently, other than in relation to a communication dated 22 December 1998 (see paragraph 7.63 below) there is nothing to suggest that the GP knew of the finding.

7.56 The full findings relating to the explanted liver were recorded in a pathology report dated 25 April 1996.[127] The external appearance was reported to be that of a macronodular cirrhotic liver showing a number of nodules of varying sizes. On section, the left lobe was found to contain a tumour mass of at least 4 x 3 x 3cm showing areas of necrosis as well as a large cystic necrotic cavity 2cm in diameter and a number of adjacent separate nodules, some of which showed necrosis. A separate nodule 2cm in diameter also displayed extensive necrosis. Throughout the right lobe there were several nodules that did not show significant necrosis but one, 2.5cm in diameter, showed extensive necrosis. In a summary of micro-examination it was noted that there were at least five separate nodules showing features of hepatocellular carcinoma on the left lobe and a further three tumours on the right lobe.

7.57 Following his transplant surgery, Mr Black was transferred to the main ward of the LTU on 22 April 1996.[128] Apart from a weekend at home, he remained in hospital until 13 May.[129] During that time, his In-Patient Clinical Notes did not refer to cancer in the explanted liver. The letter sent to Mr Black's GP after review on 29 May 1996, noted as diagnosis: 'liver transplant for Hepatitis C related cirrhosis and Haemophilia A'.[130] On 17 June Mr Black returned to hospital when his notes recorded three diagnoses: Haemophilia A, Hepatitis C cirrhosis and that Mr Black was cytomegalovirus positive. In a side note it recorded: '(incidental HCC at op)' without further detail.[131]

7.58 The detailed pathology report dated 25 April 1996 was not in the copy of the hospital records originally recovered by the Inquiry from the Crown Office. On 17 December 2010, the Central Legal Office wrote to the Inquiry with the information that an unnamed haemophilia clinician had noted that a pathology report did not appear to be included in the records. With the letter were enclosed copies of a number of reports including a copy of the report dated 25 April 1996. The copy,[132] which appeared to be a print of an electronic record, was thereafter used during the Oral Hearings.

7.59 Copies of the records of the LTU came to hand after the completion of the Oral Hearings. The original paper records had been scanned on 13 August 2012 and then destroyed. The LTU retains patients' records in electronic form in its TRAK record system and routinely destroys paper records. Electronic and hard copy prints of Mr Black's LTU records were sent to the Inquiry on 16 August 2013. They contained a further copy of the pathology report of 25 April which was initialled by Dr Bathgate, showing that the report had been received from pathology and entered the LTU records for Mr Black. The precise date when that occurred is not known but it was probably entered around the date it bears. Dr Bathgate explained in a letter dated 13 December 2013 that, at that time, written reports of explant pathology were routinely sent to the LTU doctors' room.[133] The transplant registrar was responsible for signing all laboratory reports before they were filed in the paper records of the LTU. The reports were reviewed at meetings of the consultant hepatologists and gastroenterology registrars held on Mondays at lunchtime. At the time it was not LTU practice to discuss explant pathology with patients while they were recovering from surgery. That remains the practice at present.

7.60 It is clear from the evidence, and in particular from Dr Bathgate's letter, that the report of 25 April 1996 which he initialled as transplant registrar was at all material times contained in the paper and electronic records of the LTU relating to Mr Black and available to the clinical team looking after his interests from time to time. Dr Bathgate ceased to be transplant registrar at the end of April 1996. He was replaced by Dr Khalid Bzeizi.

7.61 As already indicated, Mr Black was reviewed regularly at the LTU between May 1996 and July 1998. Letters to his GP reporting his progress frequently noted as his diagnosis as liver transplant for Hepatitis C, related cirrhosis and Haemophilia A. His history of hepatocellular carcinoma and the risk of recurrence were not mentioned.

7.62 So far as the Inquiry has been able to discover, the next reference to the condition of the explanted liver after June 1996, was in December 1998. The clinical notes for 9 December said that Mr Black had been admitted for liver biopsy, noting abnormal LFTs and '?HCC recurrence'.[134] An explanatory note stated: 'Liver transplant for HCV cirrhosis 1996 Apr incidental HCC at operation', effectively repeating the note made on 17 June 1996. A subsequent note on the same day commented: 'note incidental HCC at OLT - (P) USS today + biopsy at that time ...'.[135] The reason for this procedure was Mr Black's continually raised liver function test scores.[136] On 10 December, it was reported that radiology and ultrasound scanning found no focal lesion.[137] Liver biopsy was performed and the provisional report showed changes compatible with recurrent Hepatitis C.[138]

7.63 The discharge letter following these procedures, dated 22 December 1998 and sent to Mr Black's GP, listed under 'Diagnosis':

1. Liver transplant for hepatitis C cirrhosis - April 1996

2. Five small HCC in explanted liver (undiagnosed pre transplant)

3. Previous haemophilia

4. Abnormal liver function tests secondary to recurrent hepatitis C.[139]

7.64 Although the second item in the list did not accurately reflect the information contained in the pathology report of 25 April 1996, it notified the GP that there had been cancer in the explanted liver.

7.65 With the exception of the (inaccurate) 'Diagnosis' in the letter of 22 December 1998, hepatocellular cancer was not mentioned in the letters sent to Mr Black's GP, nor does it appear as an issue in the records up to that point, with the exception of the entries of 9 December 1998. There is nothing to suggest that the understanding reflected in the letter of 22 December was treated as significant.

7.66 Mr Black showed an interest in his risk of cancer in general. For example, in November 1998, when he was seen at the LTU,[140] he was concerned about spots on his forehead and neck because he had previously had malignant spots removed from his back. He was referred to a dermatologist to exclude the possibility of malignancy; in the event, Mr Black required minor surgery for the removal of two basal cell carcinomas. The dermatologist's history noted previous Haemophilia A and Hepatitis C infection at liver transplant in 1996 only[141] and there is no evidence that the dermatologist was aware of the cancer in Mr Black's explanted liver: there was no reference to it in the records of the dermatologist's examination of Mr Black. If Mr Black had known of his previous hepatocellular cancer, he might have discussed it with the dermatologist examining the spots for malignancy. If that had been recorded, it would have been significant. It might not have been recorded even if Mr Black did mention it, however, and little turns on the absence of any record.

7.67 Mr Black continued to be monitored. He was reviewed at the LTU in February 1999. The letter following this review, in common with other letters from the Unit up until this time (with the exception of the letter of 22 December 1998), set out the diagnosis as follows:

1. Liver transplant for hepatitis C cirrhosis - April 1996

2. Previous haemophilia

3. Abnormal liver function tests, recurrence of hepatitis C.

7.68 There was again no reference to hepatocellular cancer in the explanted liver.[142]

7.69 With one exception, the hospital reports continued in the same way until cancer was again diagnosed in the liver in 2003.[143] A record sheet dated 13 March 2002 of what appears to have been part of a research exercise, had commented: 'HCCs found in removed patient's liver' without further comment.[144] Other records from the same date contain no similar reference.

7.70 In 1996, routine pre-operative imaging for transplant assessment in Edinburgh involved ultrasound scanning of the liver.[145] Ultrasound examinations in 1994 and 1995 reported that there were no focal lesions or masses. Ultrasound examination on 2 November 1995 showed a 'very shrunken cirrhotic liver', but 'nil focal'.[146] The policy in 1996, where hepatocellular cancer was recognised prior to transplant or discovered in the explanted liver, was to continue ultrasound scans and measurement of serum alpha fetoprotein every six months after transplant.[147] The records show that serum alpha fetoprotein was regularly monitored in Mr Black's case. Ultrasound examinations of the liver graft were also recorded. It would not, however, be possible to infer that these steps were taken in pursuit of the protocol described or that they implied actual knowledge of the cancer in the explanted liver. Mr Black was seen much more frequently than the protocol required and this issue was not raised.

7.71 The Inquiry asked Dr MacGilchrist to investigate the medical records in an attempt to explain the omission from them of a full record relating to the pathology in Mr Black's management. He did not discover an explanation. He reported on his review of the records on 1 March 2011.[148] Dr MacGilchrist speculated that the finding was somehow overlooked, which would explain why it was not discussed with Mr Black's family and, by implication, with Mr Black himself. In his report Dr MacGilchrist apologised to Mr Black's family for any distress caused by the disclosure of the existence of cancer in the explanted liver. It is clear from the report that he would have expected the discovery of such an extensive multifocal carcinoma as in Mr Black's case to have been discussed with the patient at the time. Dr Mutimer said that this was information that should have been shared with the patient.[149] That was not done.

7.72 In answer to Mr Anderson, counsel representing NHS interests, Dr Mutimer dealt with the suggestion that there might have been no benefit in telling Mr Black, who was clearly an anxious man:

I think it is honesty really. It is providing the patient with information that will be of interest to him and it may actually determine his attitude to his illness and his recovery. So I think it's appropriate to discuss it with him. You are quite right that it may have unfortunate consequences in causing anxiety and the cancer may never recur, in which case in retrospect you might look back and say, "I wish we had never told him," but I don't think we are in a position to manage patients like that. This is important information that should have been shared with the patient ....

I think there are circumstances in medicine where it might be suggested that it is in everyone's interest, including the patient's, for information to be withheld, but I don't see that in this case.[150]

7.73 The discharge letter of 21 May 1996 sent to Mr Black's GP should have included reference to the cancerous tumours. Mr Black's subsequent management ought to have been informed by the findings from the explant pathology report and steps should have been taken to ensure that Mr Black was aware of them. Notwithstanding Dr MacGilchrist's research and the Inquiry's investigations, no evidence has been uncovered that might explain the omission to discuss the report. It appears that the pathology report was overlooked throughout the relevant period, as Dr MacGilchrist and Dr Bathgate suggested. That would be consistent with the clinical notes and correspondence in the medical records.

7.74 Mr Black was seen by consultants following the rota system in operation. That system has considerable advantages for patients, who are assured of regular attention from senior staff, which would be less easy and perhaps impossible to secure if the patient was under the exclusive attention of a single individual.

7.75 So far as the Inquiry is aware, the omission to inform Mr Black of the cancer in his explanated liver was a unique lapse. With the exception of the group discussions, the records of the LTU were comprehensive. There was no lapse in record keeping. The failure related to the use of the records available. Responsibility for the RIE at the time lay with the Royal Infirmary of Edinburgh National Health Service Trust and now lies with the Lothian Health Board. Standard protocols for the preparation of records of team discussion appear to be management matters for the Board.

Treatment for Hepatitis C

7.76 The procedure of liver transplantation 'cured' Mr Black's haemophilia because the transplanted liver produced Factor VIII. Reinfection of the liver with Hepatitis C was inevitable, however.[151] The Hepatitis C virus would not have been cleared by the transplant procedure and the new liver was vulnerable to infection. Further, treatment was not without complications and there was a low level of success.

7.77 Dr Mutimer said in his report:

According to the records, the possibility of antiviral therapy was discussed with the patient on a number of occasions during 1999, 2000, 2001 and 2002. At that time, there were few published data to encourage the use of antiviral therapy for Hepatitis C after transplantation. It was recognised that the results of Interferon treatment were poor with very few patients cured. In addition, it was recognised that Interferon was associated with significant side effects and that treatment could precipitate rejection of the transplanted liver.

[T]he year 1997 saw the first report of combination antiviral therapy for transplanted patients .... Compared with Interferon alone, it appeared that the combination therapy was more likely to be successful ....

Between 1997 and 2002, the peer-reviewed medical literature included approximately 10 small reports that described the results of combination antiviral therapy. The average cure rate in those reports was less than 20%. Therefore, the results of treatment were still disappointing and side effects were significant ....[152]

7.78 Dr Mutimer thought that the decision Mr Black took to decline treatment up to December 2002 was quite understandable.[153]

7.79 It must remain a matter for speculation how Mr Black might have responded to information about the cancer in his own liver. It might have influenced him, especially if he was informed about the risk of recurrence of cancer in the transplanted liver, and made him more receptive at an earlier stage to proposals that he should have treatment after his liver transplant in 1996. In general, it is clear from the evidence of Dr Mutimer in particular that Mr Black was entitled to have all information that might have had a bearing on his attitude to treatment.[154] It is not possible to form a view on whether a different course of management would have been adopted, but that might have happened if Mr Black had been fully informed.

Consequences of not detecting cancer pre-transplant

7.80 As events turned out, the fact that cancer was not detected in Mr Black's own liver before the transplant in 1996 was not altogether to his disadvantage. Dr Mutimer summarised the position disclosed in the pathology reports from 1996.[155] The explanted liver showed extensive primary liver cancer, as already narrated.

7.81 In view of the size of the largest tumour, 4 x 3 x 3cm, it might have been expected that it would have been seen on imaging before the transplant operation. That did not happen. The chance of discovery depended on the procedures followed and on the equipment available at the time. Ultrasound examination of the liver was routine in pre-transplant imaging assessment in Edinburgh in 1996 but that technology might have failed to detect even the extensive and numerous tumours found in the explant. Subsequently, more advanced imaging techniques became available and, had they been available in 1996, the lesions may well have been detected.[156]

7.82 Had Mr Black's cancer been discovered pre-transplant, and follow-up investigations carried out which disclosed tumours of the number and size involved in both the left and right lobes of the liver, it is likely that Mr Black would have been considered unsuitable for transplant. Dr MacGilchrist concurred with Dr Mutimer's view that the risk of tumour recurrence was proportional to the size and number of tumours in the liver and commented that only patients with a limited size and number of tumour nodules were considered suitable for transplant.[157]

7.83 The transplant was carried out, however, and that prolonged Mr Black's life. It also created the context for later developments, and for the question that now arises.

Recurrent or new tumour?

7.84 If, as was to happen, Mr Black did have a transplant and cancer developed in the new graft, there would be two possibilities: either this would be a recurrence of the original tumour or development of new tumour in the transplanted liver. That issue arose for discussion among senior clinicians when cancer in Mr Black's liver was next diagnosed in 2003. It was seven years after transplant and an unusual development. Dr MacGilchrist agreed with the conclusion reached at the time: that it was most likely to be a new tumour rather than a recurrence.[158]

7.85 Dr Mutimer thought, as did Dr MacGilchrist, that having regard to the number and the size of the tumours in the explanted liver, there had been a significant risk of recurrence in Mr Black's case. On the other hand, seven years was an unusually long period before recurrence: it was usually found within two years. He had hardly ever encountered a period as long as five years. The length of the period did not completely resolve the question whether this was a recurrence or a new cancer, however. Dr Mutimer was reminded during his oral testimony that the annual ultrasound examination in 2002 showed no evidence of cancer.[159] He said that indicated that any cancer, if present, was extremely small, probably less than one centimetre in size but that possibly the cancer had not yet developed.[160] In his view, post mortem findings did not indicate whether the cancer represented recurrent cancer or a new cancer in the graft.[161]

7.86 Dr Mutimer said:

I think that when transplantation is undertaken in the presence of cancer, we know that there is a proportion of cases where the cancer will recur following transplantation and there are no established strategies which will prevent that and, once recurrence does occur, if it is recurrence, then there are no proven therapies to prolong life ....

[T]he other possibility [is] that this is a new tumour. We know that when there is cirrhosis, there is a risk for cancer, and cirrhosis had developed in the graft, so it is possible that the cancer arose merely in the graft rather than representing cancer which had been lurking for seven years and then recurred as a form of recurrent cancer.[162]

7.87 Dr Mutimer thought that forensic pathologists might have or be able to develop techniques for differentiating the possibilities.[163] The known techniques involved ascertaining the gender of the tumour and comparing it with the sex of the recipient. In this case, if the tumour was female, then the tumour would definitely be of donor origin. If the donor had been male, however, that avenue of investigation would not be open. In this case the donor was male.[164] It seemed that further exploration of developing technology would not have assisted the Inquiry in resolving the issues raised by the Terms of Reference and that the researches that he suggested as possibilities would not have been a worthwhile exercise in this case.

7.88 If the fatal cancer was a recurrence, Dr MacGilchrist's view was substantially the same as Dr Mutimer's: if the patient is unlucky enough to develop a recurrent tumour, it is almost invariably incurable.[165] If Mr Black's tumour was a recurrence of the cancer in the explanted liver, nothing could have been done to prevent that and there would have been no reasonable possibility of successful treatment of that tumour.

7.89 The alternative hypothesis which, on balance, appears to be more likely on the expert evidence as a whole, is that this was a new tumour. That was the view of Dr MacGilchrist[166] and his colleagues, and it is consistent with Dr Mutimer's observations on the likelihood of recurrence of the original tumour.[167] In that event, it was Dr Mutimer's view that:

Antiviral therapy if given successfully during the early years after transplantation may have prevented the development of graft cirrhosis. If his hepatocellular carcinoma represented de novo cancer in the graft, then the prevention of cirrhosis by antiviral therapy may have prevented the development of cancer.[168]

7.90 As set out above, the possibility of antiviral treatment was discussed with Mr Black after his transplant when he attended hospital. He eventually began treatment in December 2002, by which time cirrhosis was established in the graft: it was, by that stage, too late.

7.91 However, on the hypothesis that it was a new tumour, Mr Black's prospects might have been improved by treatment with antiviral therapy commenced soon after transplant and before cirrhosis developed. If he had been made aware of the cancer in his explanted liver then, faced with advice about the benefits of antiviral treatment in avoiding or arresting the progression to cirrhosis, either from the outset, or at least when successful dual antiviral therapy became available, it is possible that Mr Black would have been inclined to take the advice tendered that he should undergo treatment after transplant sooner rather than later and that he should persist with it. It was Dr Mutimer's view that, if it was a new tumour, prevention of the progression to cirrhosis with successful antiviral therapy would probably have prevented a new tumour from developing. However, his opinion was that successful antiviral treatment, or cure, occurred in less than 20% of patients after transplant.[169] It is impossible to say that there was any actual disadvantage from failure to inform Mr Black: by late 2002, when dual treatment started, he tolerated it very badly and he may not have tolerated treatment at any stage. Further, it is possible that by the time dual treatment was available he had developed cirrhosis again. At most there was a possible, if remote, chance of improvement of his prospects.

7.92 As noted above (paragraph 7.81), it was the policy in 1996, where incidental hepatocellular cancer was discovered in an explanted liver, for continuing ultrasound scans to be performed and for monitoring of serum alpha fetoprotein to continue on a prescribed basis. These procedures were aimed at identifying possible tumour recurrence post transplant. Although not conforming to the protocol at the time, Mr Black did have these tests carried out and, as late as 2002, ultrasound showed no tumour. In the circumstances, he was not prejudiced by missing the chance of regular screening and, with it, possible detection of a tumour, by standard protocol monitoring.

7.93 Leaving aside these possibilities, there was no criticism of Mr Black's management as a patient. Mr Black was one of the first patients with haemophilia to receive a transplant in the UK. The procedure was a remarkable success in giving him a prolonged life. He survived for seven years from liver transplant and had more than five years of good quality life.

7.94 Dr Mutimer did not think that alternative management strategies following transplant could have changed the eventual outcome.[170] His conclusions were that:

  • Detection of the extent of the tumour in the explanted liver in 1996 would not have altered management of Mr Black's disease in 1996 immediately after the transplantation.
  • In the interval between 1996 and 2003, knowledge that there was cancer in the explanted liver would not have made any difference in his management following transplantation.[171]

7.95 It was Dr Mutimer's opinion that the failure to inform did not impact on Mr Black's medical treatment which was at all times appropriate and that his treatment was beneficial. His opinion has a material bearing on the assessment of the chance that Mr Black might have had a better outcome had he been informed of his previous cancer and elected to receive treatment earlier.

7.96 With the exception of the failure to provide information, Dr Mutimer had no concerns at all about the treatment given to Mr Black. From the time that Mr Black developed complications of liver disease, his medical management in Glasgow and Edinburgh seemed to him to be entirely appropriate.[172] Dr Colvin found no evidence of unreasonable or inappropriate treatment in this case.[173] These views are accepted, subject to the qualifications that necessarily arise from the failure to disclose the finding of cancer in the explanted liver.

Cause of death

7.97 The death certificate listed four conditions as contributing to Mr Black's death. In reverse order these charted the course of events chronologically: Mr Black suffered from haemophilia, which led to the transfusion of blood products, which caused Hepatitis C, which caused hepatocellular carcinoma in his transplanted liver.[174]

7.98 As matters transpired, there was no doubt about the cause of death in Mr Black's case. The final development of hepatocellular carcinoma was a direct result of cirrhosis caused by Hepatitis C infection, whether the cancer was a recurrence of the original tumour or was a new tumour in the transplanted liver. Mr Black had mild to moderate Haemophilia A which was appropriately treated with cryoprecipitate and Factor VIII concentrates, prior to the development of virus inactivation for Factor VIII concentrates in the mid-1980s. Infection with Hepatitis C in Mr Black's case was not avoidable and, before the introduction of pegylated Interferon and Ribavirin, specific antiviral therapy for Hepatitis C was generally ineffective. It was not surprising that the transplanted liver became infected and cirrhosed or that a hepatocellular carcinoma developed. It is a matter of agreement on the part of Mrs Black and other 'patient interest' Core Participants that there were no reasonable precautions whereby death might have been avoided and that is clearly the case.[175]


7.99 Factors contributing to the death of Mr Black were:

(i) Mr Black's death on 31 October 2003 was due to Hepatitis C infection in the transplanted liver, originally transmitted by blood products, together with hepatocellular carcinoma.

7.100 Infection with Hepatitis C:

(ii) Infection was inevitable given Mr Black's requirements for factor replacement therapy.

(iii) On the balance of probabilities Mr Black acquired Hepatitis C infection before the end of the 1960s in the course of haemophilia therapy in Scotland.

7.101 Progression of disease following transplant:

(iv) With the development of hepatocellular carcinoma in the transplanted liver, there were no reasonable precautions that might have avoided death.

(v) It is impossible to form a firm conclusion on whether the fatal tumour was a new tumour rather than recurrence of the tumour in his explanted liver but, on balance, having regard to the expert evidence as a whole, the cancer which developed in Mr Black's liver graft was likely to have been a new tumour.

(vi) Antiviral therapy, if successful, during the early years after transplant might possibly have prevented or postponed the development of graft cirrhosis.

(vii) Prevention or postponement of progression to cirrhosis through antiviral therapy might possibly have prevented or significantly postponed development of a new tumour.

(viii) It is not possible to form a view whether earlier antiviral treatment would have been successful. It is no more than a possibility - estimated generally by Dr Mutimer to be less than 20%. Mr Black's lack of tolerance of treatment from December 2002 lengthened the odds against his ability to tolerate the necessary full course of antiviral treatment whenever attempted.

7.102 Mr Black's management as a patient:

(ix) Mr Black was not told that there had been cancer in his explanted liver. Appropriate steps should have been taken to ensure that he was aware of the relevant explant findings in the pathology report. Failure to inform him was a lapse from acceptable standards of patient management.

(x) This lapse was not evidence of systemic failure. On the evidence available it was a unique occurrence.

(xi) Mr Black was entitled to have information on all relevant factors in considering whether to undergo antiviral treatment of his recurrent Hepatitis C infection. The history of hepatocellular carcinoma in the explanted liver may have influenced his decisions from 1996 and more particularly from December 1998, had he been aware of it.

(xii) Failure to inform Mr Black of the cancer in the explanted liver deprived him of the chance, however remote, of a longer life that might have followed successful earlier antiviral treatment and eradication of Hepatitis C.

(xiii) With that one exception Mr Black's management as a patient was at all times appropriate and of a high standard and reasonably related to his needs.

Eileen O'Hara

7.103 Mrs O'Hara was born on 9 October 1930. She was employed as an orderly at Stobhill Hospital from about 1980 to 1990 when she retired at age 60.[176] She died on 7 May 2003. The certified causes of death were:

I (a) Hepatic Failure

I (b) Septic Shock

II Mitral Valve Disease.[177]

Mrs O'Hara's medical history to July 1995

7.104 Mrs O'Hara had a complicated medical history, starting in about 1963, involving cardiac, obstetric and gynaecological problems.[178] It is highly likely that the significant events that may have exposed her to transmission of the Hepatitis C virus happened before November 1990.

7.105 On 11 January 1963, Mrs O'Hara had surgery for mitral stenosis (narrowing of the mitral valve of the heart).[179] The background to that condition was rheumatic heart disease: Mrs O'Hara had rheumatic fever as a child, probably in the late 1930s or early 1940s.[180] It was a common disorder in Scotland up to the late 1940s. With its origin in streptococcal infection, until penicillin became widely available, after about 1945, there was no effective treatment for the infection. Additionally, without the benefit of antibiotic treatment in childhood, the patient often presented later with the heart manifestations of rheumatic fever which specifically affected the heart valves, often leading to stenosis.[181]

7.106 In early 1963, bypass procedure during surgery had not been introduced.[182] Treatment for mitral stenosis involved adjustment of the valve by manual valvotomy.[183] In this procedure, the chest was opened, usually under the left breast. A vent was inserted and the surgeon used his fingers to enter the left atrium of the heart and widen the mitral valve.[184] It was a skilful, but quite brief, operation and frequently it did not require transfusion. The available records did not resolve the question of whether Mrs O'Hara had received a transfusion in 1963 but left it open as a possibility. However, in November 1971 Mrs O'Hara was seen at the obstetrics department of Stobhill Hospital.[185] Her mitral valve disease was noted and it was recorded at that time that she had previously had a blood transfusion. While the source of that information was not disclosed, it suggests that it is highly likely that Mrs O'Hara did have a blood transfusion at the time of her surgery in January 1963.

7.107 In March 1972, Mrs O'Hara received a blood transfusion on the birth of her son by Caesarean section.[186] Two bottles of whole blood were issued, of which one, numbered 5209, was transfused.[187] Subsequent research by the SNBTS has shown that the blood was donated at Lockerbie on 5 March 1972.[188] There was no test for non-A, non-B Hepatitis/Hepatitis C in existence at that time.[189] There is no record of the donor having been subsequently tested for Hepatitis C.[190]

7.108 On 28 November 1979, Mrs O'Hara had a hysterectomy at Stobhill. She received one unit of whole blood and one unit of packed cells in the course of the procedure.[191] Subsequent SNBTS research again traced the donations, to Coatbridge and East Kilbride, in November 1979. There was no record of either donor having been tested for Hepatitis C at any time.[192]

7.109 In February 1984, Mrs O'Hara was seen in the medical out-patient clinic at Stobhill by Dr Francis Dunn, Consultant Cardiologist.[193] The main focus was heart disease. It was noted that liver function tests (LFTs) were abnormal and it was suggested that this might be a consequence of her mitral valve disease: patients with mitral valve disease likely to require surgery were also likely to have mild abnormalities of liver function.[194] At that stage, before successful replacement of her mitral valve, Mrs O'Hara had significant heart failure; pressure on the right side of her heart was significantly elevated in 1985 and that would have given rise to back pressure on the liver, leading to abnormal LFTs.[195] That was a reasonable view at the time according to Dr David Mutimer, Consultant Hepatologist at the Queen Eliabeth Hospital, Birmingham, who provided expert evidence to the Inquiry.[196] It could not have been concluded by her doctors before that date that she had acquired a chronic liver disease.

7.110 In June 1985, Mrs O'Hara had cardiac surgery at the Glasgow Royal Infirmary (GRI). On that occasion a Wessex porcine bioprosthetic valve was inserted.[197] On 5 June, five packs of concentrated red cells were issued prior to surgery on 7 June.[198] All five were used.[199] Plasma was also administered.[200] The SNBTS was not able to trace the donors.[201]

7.111 In early 1990, Mrs O'Hara was found to have diabetes mellitus.[202] Although her diabetes was initially controlled by diet, on 7 March 1990 her GP referred her to Stobhill Ophthalmology after an optician reported having found some signs of diabetic retinopathy (damage to the retina caused by diabetes).[203] Ocular examination at Stobhill was unremarkable, however, and she was discharged in to the care of her GP.[204]

7.112 Later in 1990 Mrs O'Hara became unwell. Her GP arranged liver function tests, which were found to be mildly deranged. The GP told her that there were problems with the results and referred Mrs O'Hara to the GRI for tests on 29 May 1990.[205] In her referral letter, the GP wrote that Mrs O'Hara did not take any alcohol and wondered whether drug therapy was the cause of her abnormal LFTs.[206] Mrs O'Hara continued going to the GP 'for several months'.[207] It seems to be in the context of those visits that consumption of alcohol was raised, presumably because she had persistently abnormal liver blood tests. Mrs O'Hara's daughter, Mrs Roseleen Kennedy, said that her mother had commented that the GP kept asking her whether she was drinking. In fact, she drank very little and became upset that she appeared to be being dealt with as an alcoholic.[208] Given her liver function test results, however, questions about alcohol consumption were routine. As reported in the letter to the GRI, the GP accepted that Mrs O'Hara did not drink alcohol.[209]

7.113 The GRI's report to her GP on 1 June 1990 stated that Mrs O'Hara's cardiac position was good. No hepatic enlargement was identified on examination in hospital. The GP was, however, encouraged to continue with liver function tests and to seek ultrasound tests or a gastroenterologist's report if her liver function tests continued to show mild derangement.[210]

7.114 In September 1990, the GP referred Mrs O'Hara to the GRI Gastroenterology Department commenting that she had mild persistent derangement of her LFTs and frequent loose bowel motions. The GP noted that Mrs O'Hara had only ever taken a moderate amount of alcohol and that her liver function tests were still deranged on abstinence.[211] In a full report dated 5 November 1990, the gastroenterology registrar, Dr J Morris, set out the clinical findings on examination that day.[212] Significantly, the tip of the spleen was palpable. Overall, it was thought that she had mild congestive cardiac failure. Dr Morris did not feel that this explained her abnormal blood tests, however.

7.115 In her history so far Mrs O'Hara had experienced a significant exposure to blood transfusion. Dr Morris did not have that information available when examining her. In his letter to the GP on 5 November 1990, he wrote:

Although I was unsure whether she received blood transfusions with her various operations in the past ... I suppose this remains a possibility and I have therefore checked hepatitis screens including hepatitis C, further I have rechecked liver function tests, urea and electrolytes, chest x-ray, ECG, echocardiogram auto antibodies and an abdominal ultrasound. I think it is important that we check on the function of her valve replacement to [see] whether there is any regurgitation contributing to heart failure. Secondly we have persistent abnormal LFTs and hopefully the above investigations will give some idea of how we should proceed with further investigations. This may well be on the basis of a liver biopsy should the other investigations fail to turn up a clue to the problems.[213]

7.116 Blood was taken for hepatitis tests on 5 November 1990. Dr Morris wrote to Mrs O'Hara's GP on 4 December, observing that the recent investigations had shown a fair degree of valve dysfunction that would need to be looked at further.[214] By then the results of some tests had been reported by the GRI Microbiology Department. HBsAg tests (for Hepatitis B) were negative;[215] the IgM anti-HAV (for Hepatitis A) test was negative;[216] Epstein-Barr virus and Cytomegalovirus had not been detected.[217] The test for Hepatitis C antibody was not reported until 18 December 1990: it too was negative.[218] Dr Morris said he would write to Mrs O'Hara with a view to bringing her back to the clinic to discuss the results.

7.117 Dr Morris duly wrote to Mrs O'Hara on 4 December 1990, enclosing a clinic appointment for two weeks later.[219] He saw her on 17 December. According to a file note prepared in January 1991, Mrs O'Hara remembered a series of tests, including an ECG, being carried out at the 17 December appointment. She was told that she would be referred to Cardiology and that she would receive an appointment in the near future.[220] She was referred to Dr AR Lorimer, a cardiologist at the GRI, by Dr Morris on behalf of Dr JF MacKenzie, the Senior Consultant, on 17 December.[221] In his letter to Dr Lorimer, Dr Morris referred to her raised LFT results and said:

The most striking abnormality, however, on examination was evidence of both mitral and tricuspid regurgitation .... An Ultrasound of the abdomen shows the liver and spleen to be enlarged with splenic vein dilatations. Overall, these are the appearances we would expect with congestion secondary to primary cardiac abnormality. Certainly we feel that this is the most likely cause of her abnormal liver function tests.

7.118 Mr El Fiky from Cardiothoracic Surgery at the GRI saw Mrs O'Hara on 18 January 1991. His clinical findings supported Dr Morris. An echocardiogram had shown that her heart valves and consequent heart failure were more severe than had been expected and he recommended that she should have an early appointment at Dr Lorimer's clinic with a view to mitral valve replacement as soon as possible.[222] Dr Lorimer saw her and reported to her GP on 7 February.[223] He found signs of a degree of incompetence and stenosis of the valve. He reported that the liver was not unduly enlarged that day. He suspected a further myocardial factor and arranged for her admission for further, more detailed evaluation.

7.119 She was duly admitted to the GRI on 25 February 1991. She was seen by Mr Dimitri of the department of Cardiac Surgery, where cardiac catheterisation and transoesophageal echocardiogram investigations were carried out to investigate her mitral valve.[224] The discharge notes recorded that Mrs O'Hara had 3cms hepatomegaly (enlargement of the liver) which was slightly tender. LFT results were reported to be normal apart from slightly raised Gamma-glutamyltransferase (GGT, an enzyme found in many body tissues but especially the liver. Elevated GGT can be a marker of liver disease).[225] This minor abnormality was not considered to be significant.

7.120 Mr Dimitri reported to Dr Lorimer on 7 March. Clinically, Mrs O'Hara had signs of prosthetic malfunction and was in atrial fibrillation (deviation from the normal rhythm of the heart) and there was stenosis (narrowing) of the valve. It was noted on examination that her increased hepatomegaly suggested a progressive enlargement of the liver.[226] Mr Dimitri commented that replacement of her mitral prosthesis was required but suggested to Dr Lorimer that an angiogram might be appropriate to delineate her coronary anatomy.

7.121 Meanwhile, a further appointment had been arranged for Mrs O'Hara to attend the Gastroenterology Clinic at the GRI on 11 March 1991. She did not attend, however. The consultant gastroenterologist, Dr MacKenzie, thought this might be explained by the fact that she had just returned home from her hospital admission (she had been discharged on 1 March) and wrote to her GP that she would be sent another appointment for a month later.[227] Investigations have not shown whether or not Mrs O'Hara or her GP asked for or received a further appointment. There is no evidence in the medical records that she attended Gastroenterology about this time.

7.122 On 8 April 1991, Professor Lorimer, as he had become, reported to Mrs O'Hara's GP, copied to Mr Dimitri, with the GRI's clinical summary commenting that she was a candidate for mitral valve replacement and confirming that she was on his waiting list for the further investigation proposed by Mr Dimitri.[228] The GP had written to Professor Lorimer on 17 May questioning the need for further coronary angiography[229] but the procedure was carried out in July 1991. Her coronary arteries were normal. It was decided that Mrs O'Hara would go forward to mitral valve replacement and that otherwise her management should continue on current lines.[230] Mr Dimitri confirmed in a letter to Professor Lorimer on 30 July that she would be admitted for replacement of her mitral prosthesis.[231]

7.123 The mitral valve replacement surgery was delayed for family reasons. Mrs O'Hara was admitted on 15 October 1991. She had a valve replacement with a St Jude bileaflet mechanical valve on 18 October 1991.[232] The procedure was successful.

7.124 Mrs O'Hara was monitored at the GRI. She was seen at Mr Dimitri's clinic on 17 December 1991 when it was noted that her recovery had been quick and smooth, that she was doing well and had no complaints.[233] She was reviewed in February 1993.[234] There were no symptoms of heart failure and her prosthetic valve was functioning normally. Her next annual review, in February 1994, was unremarkable.[235]

7.125 Mrs O'Hara was referred to the Diabetic Day Unit at Stobhill in August 1994. On examination there, she was found to have hepatosplenomegaly (enlarged liver and spleen). The consultant physician, Dr McLaren, who was surprised at the finding, thought that it might be secondary to her mitral valve replacement and proposed writing to the cardiac unit at the GRI. If hepatosplenomegaly had been noted before it was unlikely to be significant. If it was new, however, he thought that an ultrasound examination, at least, would be required.[236] He wrote to that effect on 5 August 1994.[237] He was to find the reply from the cardiothoracic surgeon less than illuminating:

In the absence of gross failure it would be appropriate to investigate the hepatosplenomegaly. I suspect that we will not find anything but nevertheless there is justification for doing so.[238]

7.126 On 16 August 1994, Dr McLaren wrote to Mrs O'Hara's GP.[239] He said he had received a 'rather delphic communication from the cardiothoracic surgeons, the burden of which ... is that they have not noted hepatosplenomegaly before'. Further investigations were put in hand. Dr McLaren arranged for an ultrasound of her abdomen. On 9 September, Dr McLaren wrote again, confirming that Mrs O'Hara had very marked splenomegaly (enlarged spleen) and mild hepatomegaly. A biochemical screen on her last visit had been normal but he had done a full blood screen and arranged ultrasound examination.[240] On 22 September, Dr McLaren intimated the results of tests.[241] Ultrasound tests had confirmed the presence of splenomegaly and suggested a degree of portal hypertension (high blood pressure in the portal vein system at the liver). He suggested, correctly, as events were to prove, that the findings might all be secondary to cirrhosis.

7.127 Dr McLaren saw Mrs O'Hara again on 19 October 1994. Mrs O'Hara told him that she had previously been told there was 'something wrong with her liver' due to her heart disease. Dr McLaren's report to the GP reflected some annoyance. Hepatosplenomegaly had been noted in 1990 and he asked for correspondence from the GP's records which might relate to the topic. Further ultrasound examination had confirmed the presence of hepatomegaly and there was further indication of cirrhosis.[242] The GP responded on 4 November 1994, enclosing the GRI report of 3 April 1991 and confirming that Mrs O'Hara had deranged LFTs in January 1994.[243]

7.128 Following discussions between Dr McLaren and Dr Dunn, Mrs O'Hara was seen in the department of cardiology, Stobhill, on 21 December 1994 by Dr Dunn and Dr Tait, the registrar in cardiology. The registrar subsequently reported to Dr McLaren and to the GP.[244] The letter noted that Dr McLaren had detected hepatosplenomegaly and that possible fat infiltration of the liver had been detected with prominence of the portal vein and marked splenomegaly. Dr Mutimer thought, in retrospect, that any fat infiltration was probably related to Mrs O'Hara's diabetes.[245] The letter also acknowledged that abnormalities in liver function tests had been detected in 1990, with hepatomegaly and with the tip of the spleen possibly being palpable. It was noted that the slight enlargement of the liver and spleen found in 1990 were attributed to right heart failure consequent to mitral re-stenosis with a degree of pulmonary hypertension. The liver abnormalities did not appear to have been re-checked following her mitral valve replacement in 1991.[246] Her condition on clinical examination was reported. The conclusion reached was that an alternative cause for her hepatosplenomegaly appeared to be indicated and required investigation.[247] Dr Dunn explained that, because of the success of the mitral valve procedure and her satisfactory cardiac status at the time, it was unlikely that the condition of her liver and spleen was related solely to her heart disease.[248]

7.129 Investigation of Mrs O'Hara's liver was initiated by Dr Tait.[249] Dr Dunn explained that, at that time, doctors in his department were often 'gatekeepers,' doing initial investigations before referring on for other specialist consideration.[250] Hepatitis testing was carried out and reported in February 1995. It was confirmed that Mrs O'Hara was positive for Hepatitis C antibody.[251] Dr Mutimer explained that this test confirmed that she had been exposed to Hepatitis C at some stage but not whether the virus was still present.[252] Later tests confirmed that it was.[253]

7.130 Mrs O'Hara was reviewed at Stobhill cardiology clinic on 27 February 1995.[254] She had developed herpes zoster (shingles) affecting her leg and abdominal wall. Typically, the condition causes pain and, in Mrs O'Hara's case, irritation of the nerves continuing after her rash had resolved. She had been admitted to hospital as an emergency as a result of this complication, known as post-herpetic neuralgia.[255] Further investigation of her hepatosplenomegaly was delayed until she was feeling better.[256] However, investigation continued and Dr Dunn reported to her GP on 29 March 1995.[257] Mrs O'Hara's case had been discussed with gastroenterology colleagues and it was agreed that liver biopsy was indicated. Advice was given on her continuing cardiac issues. Dr McLaren wrote to the GP on 3 April.[258] He reported on her herpes zoster infection. In addition he commented on the possibility that the antibodies against Hepatitis C (indicating Hepatitis C infection) that had been identified were attributable to blood transfusions and suggested that would explain why she might have developed cirrhosis, the presumed diagnosis. Fuller, subsequent, evaluation was to prove that he was probably right.[259]

7.131 On 12 May 1995 Dr Dunn reported to the GP on the results of CT scanning of Mrs O'Hara's abdomen.[260] There was significant hepatosplenomegaly and, in particular, splenomegaly. It was suggested that the condition of her lymph nodes might have a malignant source, for example lymphoma.[261] This was to prove a false trail.

7.132 Bone marrow and liver biopsy investigations were carried out in June and July 1995.[262] The tests were related to the risk of a malignant source of her lymph node condition.[263] There was no evidence of lymphoma or of malignancy.[264] There was no evidence of malignant infiltration of the bone marrow. The strong likelihood was that the 'enlarged lymph nodes' that had prompted discussion of lymphoma were in reality enlarged blood vessels in the abdomen resulting from portal hypertension (as had been suggested in September 1994). Liver biopsy showed cirrhosis with lymphocytic infiltrate, appearances that were typical of Hepatitis C.[265] The lymphocytic infiltrate was an indication of the body's immune cells reacting to the presence of the virus in the liver.[266] Mrs O'Hara was told that she had cirrhosis.[267]

Mrs O'Hara's medical history after July 1995

7.133 Until about mid-1995, Mrs O'Hara's liver disease was relatively asymptomatic. She appeared to her daughter to have been well until June of that year. She looked after her granddaughter, born in 1992, from the point when Mrs Kennedy returned to work, until June 1995. At that point, Mrs O'Hara began to appear unwell and complained of fluid retention in her legs and of a swollen abdomen. She looked pale and tired, felt nauseated and started to lose her appetite.[268] Mrs Kennedy said that her mother slowly deteriorated from 1995.[269] The family account of Mrs O'Hara's general health was a reasonable fit with her medical history. In the period 1991-94, as noted later, she frequently attended her GP for relatively minor ailments. Late 1995 was the time when Mrs O'Hara began undergoing extensive and continuing investigations.

7.134 After July 1995, when the diagnosis of cirrhosis was finally arrived at and intimated to Mrs O'Hara, matters did not progress swiftly for a time. Mrs O'Hara continued to attend her GP with relatively minor complaints.[270] She was examined following spontaneous haemorrhage in her left eye on 29 July. On 3 August, she reported pain in her left shoulder. Co-codamol was prescribed but did not help. Pain in the back of her neck was extending to her hand. Her shoulders were stiff and she had chest pain. She also reported vomiting and sweating.[271] After review of the findings in September 1995, Dr Prasad, a Stobhill cardiologist, indicated to the GP that Mrs O'Hara should be reviewed by Dr Forrest, consultant gastroenterologist at Stobhill.[272] A letter of referral was sent to Dr Forrest on 12 September 1995.[273] Enclosed with the letter was a copy of Mrs O'Hara's 'recent clinic letter', which appears to have been Dr Prasad's letter to the GP. It stated:

This lady who was sent to our clinic with possible congestive cardiac failure was found to have hepatosplenomegaly and subsequently has been investigated by the haematologists and ourselves. The liver biopsy showed cirrhosis with lymphatic infiltrate. The appearances were non-specific but in keeping with Hepatitis C .... In view of these findings I think in the first instance we should ask our Gastroenterology colleagues to review her and further assess the need for additional treatments such as Interferon .... I will arrange to see her again in four months time but we will wait until Dr Forrest's review.[274]

7.135 In 1995 Stobhill Hospital was managed, and its consultants were employed, by Stobhill National Health Service Trust. Responsibility for the hospital and its staff now lies with Greater Glasgow Health Board.

7.136 Dr Forrest replied on 3 November 1995, without seeing Mrs O'Hara. Since this represented a significant stage in her care it is appropriate to quote from his letter:

I note that she was found to have hepatosplenomegaly around 1990 and that a recent liver biopsy shows an established cirrhosis. This could be idiopathic [of unknown origin] but could be related to Hepatitis C, but there is no obvious continuing Hepatitis from the biopsy report.

If her cirrhosis is due to Hepatitis C (and of course it could be cryptogenic [another term indicating unkown origin]) then she must have contracted her Hepatitis C very many years ago as cirrhosis develops very slowly following infection with Hepatitis C.

Interferon has been used for Hepatitis C but the results in terms of clearing the virus from the patient's serum are disappointing. Perhaps only around 25% of patients will respond on a long term basis and all the evidence suggests that patients who are cirrhotic have a much lower response rate than this. The other factor is that Greater Glasgow Health Board has instructed the General Practitioners not to prescribe Interferon for chronic Hepatitis C and the Trust will also not prescribe it. The Health Board have apparently given £200,000 for a trial to be started at the Royal and the Western. At the present time I have not seen the protocol to see which sort of patients would be suitable for treatment, but I doubt if this lady would be a candidate. Having said that I will arrange to review her liver biopsy to see if there is any ongoing evidence of Hepatitis and will write to you further after that.[275]

7.137 On 30 November 1995, Mrs O'Hara was seen at Dr Dunn's clinic.[276] The cardiac findings, in context, suggested that her cardiac status overall was stable.[277] Dr Dunn explained that his department remained reasonably happy with Mrs O'Hara's heart condition at this time and this remained the case up to about 1998.[278]

7.138 Dr Bong (Senior House Officer, Department of Cardiology, Stobhill) renewed the request to Dr Forrest for advice in March 1996.[279] Dr McLaren reminded Dr Forrest of the request in May.[280] By letter from a senior registrar in Cardiology, which was dictated on 28 June and typed on 12 July, Mrs O'Hara's GP was told that Dr Forrest planned to review her case on the day of dictation and that the GP would hear directly from Dr Forrest.[281]

7.139 Dr Forrest reviewed Mrs O'Hara's liver biopsy but did not see her in person. He wrote to Dr McLaren on 10 July 1996 apologising for his delay in responding. He confirmed that her liver biopsy in 1995 showed established cirrhosis and that he had reviewed the biopsy recently.[282] He thought that she did not need a repeat liver biopsy. He doubted very much whether she was a candidate for Interferon treatment. Dr McLaren wrote directly to Mrs O'Hara and to the GP passing on the information from Dr Forrest that repeat liver biopsy was not necessary.[283] These matters are discussed more fully in paragraphs 7.202-7.211 below.

7.140 Mrs O'Hara was seen at Stobhill Department of Haematology on 21 April 1997.[284] She had been referred because of her neutropenia and thrombocytopenia (reductions in white cell and platelet counts in the blood respectively), both of which are observed in patients with cirrhosis.[285] She had hepatosplenomegaly and was anaemic.[286] The haematologist found that Mrs O'Hara was developing early iron deficiency. He arranged for further endoscopic examination to see whether she was bleeding from her upper gastro-intestinal tract as a consequence of her cirrhosis. Subsequent endoscopic examination on 14 July 1997 showed that there were varices proximal to the gastro-oesophageal junction.[287] There was evidence of portal hypertension with the varices but it was thought that this was extremely unlikely to be the cause of her iron deficiency anaemia. There were no stigmata (signs) of recent bleeding. A report was sent to Mrs O'Hara's GP on 28 July.[288]

7.141 Dr Mutimer interpreted the report:

They would be looking for a cause of blood loss ... [T]he haematologist thinks that the patient is iron-deficient, which means there is likely to be some chronic blood loss. That can be due to the portal hypertension, it can be due to the cirrhosis. It is appropriate that she has an endoscopy for two reasons. One is to see whether the varices are present and if they are small or large, and at the same time the endoscopist can look around the stomach to make sure that there is no additional cause of blood loss, like a stomach ulcer or a stomach cancer.[289]

7.142 Mrs O'Hara was admitted to Stobhill as an emergency patient between 21 and 27 May 1999 for 'stabilisation of really quite severe cardiac failure'.[290] Dr Dunn explained that valve prostheses last a variable period of time. It appeared that some elevation of pressure was starting on the right side of the heart, leading to swelling of the ankles. Sometimes this could be reactive: it did not necessarily mean that the valve was the source of the trouble as patients often had a degree of elevation of the pressure on the right side of the heart at the time of the operation. This can be relieved but can subsequently return and the tricuspid valve (located on the right side of the heart) can start to dilate creating back pressure causing failure, predominantly of the right side of the heart. Ankle swelling may also occur as a consequence of cirrhosis and portal hypertension. From Dr Dunn's recollection, her problems were with the right side rather than the left side of the heart.[291]

7.143 In September 2001, Mrs O'Hara was again reviewed.[292] Her shortness of breath was stable but she reported chest pain on exertion. It was thought that the pain was likely to be ischaemic in nature (caused by inadequate flow of blood to the heart). In Mrs O'Hara's case this was probably caused by her atrial fibrillation, a heart rhythm disorder.[293]

7.144 In March 2002, Mrs O'Hara reported that medication had reduced her chest pain and, on examination, she appeared well.[294] Her medication remained as before. However, to achieve stability of her heart complaint, she required a significant dose of Frusemide, a diuretic.[295] By this time her diabetes had already become severe enough to require regular insulin treatment.[296]

7.145 Mrs O'Hara became very unwell in March 2003. She had abdominal pain and was vomiting.[297] Her GP at Springburn Health Centre thought she had pancreatitis. He referred Mrs O'Hara to Stobhill on 24 March 2003.[298] She had developed right hypochondrial (under the ribs) pain. The GP suggested urgent abdominal ultrasound examination. Her liver function tests were mildly abnormal but within her usual range.[299] A Hepatitis C PCR[300] test in April 2003 was positive, showing that the Hepatitis C virus was still present at that time.[301] A CT scan on 31 March showed pronounced hepatosplenomegaly. In addition, there were extensive varices, some of which were entwined round the pancreas explaining the previous belief, arising from the earlier ultrasound examination, that there might have been a pancreatic mass. There was no such mass. There was moderate ascites (accumulated fluid in the abdomen).[302] She had an enlarged heart. There were gallstones. The cause of her pain was severe pancreatitis.[303] The investigations did not disclose another cause of her pain.[304] In a patient of Mrs O'Hara's age, the most common cause of pancreatitis is probably gallstones and, in severe cases, it is frequent practice to try to clear stones away from the bile duct.[305]

7.146 Mr Robertson took up Mrs O'Hara's care at Stobhill. His initial likely diagnosis was gallstone acute pancreatitis.[306] Her amylase count was many times over the reference level applied at Stobhill to confirm a diagnosis of acute pancreatitis in association with her other symptoms and, in particular, gallstones.[307] She had raised INR (International Normalised Ratio: an indication of how easily the blood clots, normally measured for patients treated with warfarin).[308] After a period of conservative management that appeared to stabilise her condition, CT examination of her abdomen showed marked changes of acute pancreatitis but no obvious necrosis (death of cells or tissue) or local complication. Of the alternative approaches to open surgery, laparoscopic cholecystectomy (removal of gall bladder) was excluded by anaesthetic considerations, including the difficulty in restoring natural respiration after surgery under artificial ventilation.[309] It was therefore decided to proceed to ERCP and endoscopic sphincterotomy, procedures that could be performed under sedation.[310]

7.147 The surgical procedure, as described in evidence by Mr Robertson, to deal with Mrs O'Hara's gallstones was protracted and difficult.[311] The target area was very small and the surrounding mucosa (mucous membrane) swollen.[312] An initial procedure failed.[313] A second procedure was partly successful in that the sphincter muscle, the ampulla of Vater, was cut. Difficulties had been anticipated on account of Mrs O'Hara's other health problems and there was a risk of bleeding. The cut caused bleeding that had to be dealt with and the procedure was suspended with only partial success having been achieved.[314] A third attempt on 18 April completed the operation.[315] The bile duct was cleared of the obstructions (stones) that had gathered at its junction with the pancreas.[316]

7.148 Mr Robertson asked for cardiological and gastroenterological input to help her overall management. It was known that Mrs O'Hara had underlying liver pathology: she had cirrhosis. It was also known that she had cardiac disease and impaired heart function as a result. The control of these conditions by medication was impaired and the symptoms that they might cause were more manifest.[317] Furthermore she had insulin-dependent diabetes.

7.149 Her pancreatitis seemed to be resolving. However, she developed a tense abdomen with marked ascites, probably reflecting a combination of decompensated[318] hepatic and cardiac failure, along with a degree of hypoalbuminia (shortage of white blood cells), and cellulitis (bacterial infection of the skin) affecting mainly the lower limbs. The medication that had controlled her liver and heart disease lost effectiveness. With gastroenterological and cardiac help, she seemed to improve but there was marked oedema below the knees.[319] Mr Robertson thought that bacterial endocarditis (inflammation of the lining of the heart cavity) could have developed, but accepted the view of Dr Petrie that that was unlikely.[320]

7.150 On 3 May, Mrs O'Hara deteriorated further, with increasing confusion and shortness of breath. She was clearly moving in the direction of 'multi-organ failure', a condition that is associated with very high mortality. Consideration had been given to ventilation in the Intensive Therapy Unit but it was felt that she could not be removed from artificial ventilation once it had been commenced. Hence she was moved from the surgical unit and admitted to the coronary care unit for intensive cardiac monitoring and support.[321]

Mrs O'Hara's final admission and death

7.151 Mrs O'Hara died on 7 May 2003. Her final admission was very difficult and complicated. She had pancreatitis. Gallstones were probably the most common cause of pancreatitis in a patient of her age and it was common practice to try to clear some of these away from the bile duct. She developed cellulitis. In the course of this illness Mrs O'Hara had a lot of problems with fluid retention and that would be manifest in a couple of ways. One would be that she would develop ascites, which was seen on the CT scan, but, in addition to that, the fluid retention was likely to be more generalised and particularly to affect her lower limbs and buttocks. In those circumstances there was a susceptibility to infection because of swelling of the tissue with fluid. In the event, she developed very serious infection in those tissues.[322]

7.152 As noted in paragraph 7.103, the causes of death registered on her death certificate were hepatic failure, septic shock and mitral valve disease.[323] Mrs Kennedy had commented on the absence of reference to Hepatitis C.[324] When asked if he would have expected Hepatitis C to have been mentioned, Dr Mutimer said:[325]

Yes, it is a cause of the liver disease, so if the liver failed, then it would be appropriate that Hepatitis C is listed on the death certificate.

7.153 He was asked if, by 'appropriate' he meant that it should have been listed and he confirmed that he did.[326] In relation to pancreatitis, he added:

I think that pancreatitis seems to be missing as well ... her final illness was due to severe pancreatitis. At the end of that illness ... the cause of death was infection. That would be very typical of severe pancreatitis. The ability to cope with an illness of this severity would be affected by the fact that the patient has cirrhosis, and the cause of the cirrhosis is Hepatitis C. So the liver was not the cause of the final illness but it probably affected her potential to survive this illness, but I can't say to what extent because patients with normal livers die of severe pancreatitis in this sort of setting.[327]

7.154 Dr Mutimer explained his view that Hepatitis C infection was unlikely to have made a major contribution to shortening Mrs O'Hara's life. He said:

[I]t was certainly my view after going through all of the records ... I can only have an impression. I never saw the patient, of course, but it was my impression that her health was not very good at that stage [between 1999 and 2003] and that there was diabetes, there was possibly additional cardiac problems, possibly angina. So it is difficult in that setting to say what her prognosis would be if she did not have cirrhosis of the liver.

On balance, I think that her life expectancy was not long because of those issues. The Hepatitis C and the cirrhosis may have shortened her life.[328]

7.155 Asked to explain what he meant by 'may have shortened her life', he said:

I think "may" means a better than 50 per cent chance that it contributed but ... severe pancreatitis in a patient aged 72 is associated with ... severe morbidity and with mortality, and that can be observed regardless of the presence or absence of cirrhosis. I think that the cirrhosis may have contributed to the fact that this patient did not survive the illness.[329]

7.156 In the days leading to her death, many tests were carried out. Dr Mutimer commented on some of the results relating to her liver.[330] Having looked at the records of her prothrombin time (a measure of coagulation activity) measured by INR, Dr Mutimer confirmed his view that Mrs O'Hara's liver managed remarkably well in the early phases of this final admission, despite her severe pancreatitis.[331] In a patient with cirrhosis of the liver who developed a serious problem elsewhere, like pancreatitis or any other serious non-liver illness, then probably the best way to see whether the liver had sufficient strength to cope with the stress was to look at the patient's serum bilirubin[332] level and also the INR. It was really only at the very end of Mrs O'Hara's life that the bilirubin started to go up. Her INR was affected by warfarin. The doctors had to stop the warfarin but, when they did that, Mrs O'Hara's prothrombin time returned almost to normal values. The liver is responsible for the synthesis of several proteins required for normal blood clotting. If the function of the liver is impaired, that is reflected in prolonged INR. Normal INR implies that the liver is functioning well. Mrs O'Hara's liver was coping remarkably well during the first weeks of this really very serious illness after withdrawal of warfarin therapy. This indicated to Dr Mutimer that if she had not developed serious illness, the liver would still have had 'significant mileage' left in it.[333]

7.157 Dr Mutimer noted that, in the last few days of her illness, her C-reactive protein was very high, as was her white cell count. These were markers of very severe infection.[334] Her albumin count was indicative of severe pancreatitis.[335] She had renal failure and worsening hepatic failure in the context of overwhelming sepsis (infection).

7.158 Dr Mutimer's view of the cause of death was sepsis, due to pancreatitis, with contributory causes including cirrhosis due to Hepatitis C and diabetes.[336] Mr Robertson thought one could not express a view on her prospects if cirrhosis and Hepatitis C were removed from the equation: her morbidities were all interrelated.[337]

7.159 In his report for the Inquiry, Dr Petrie expressed the view that Mrs O'Hara had 'overwhelming sepsis, felt likely secondary to pancreatic collection. She tolerated this poorly due to her longstanding liver and heart disease and developed new acute renal failure'.[338] Dr Dunn commented:

Yes, I think that's fairly accurate. Often in these situations - I mean, acute pancreatitis is in itself a very severe illness and when the patient is afflicted with that and already has significant multi-organ difficulties, and in her case I think her diabetes and her extensive past cardiac conditions were put under the kind of stress with the pancreatitis, that while she was managing not too badly, the pancreatitis just led to a failure of these other organs. I think it is just an effect almost like a domino effect. If one system goes, then the next system goes under pressure and so on and so forth. So I would think that certainly the sepsis was the - the result of the pancreatitis was what caused this. So I would agree with that. I get the impression that on reflection, Dr Petrie felt that Hepatitis C should have been mentioned in the death certificate and I would agree with that.[339]

7.160 Dr Dunn, having re-considered Mrs O'Hara's history of diabetes, her cardiac status and Hepatitis C, said:[340]

I have looked at this again, just reflecting on it, and I think there is no doubt these factors, each of them would contribute a substantial increase, perhaps doubling. If we say that mortality from the pancreatitis was, say, 7 to 10 per cent, I think each of these factors would add another 10 per cent, perhaps not the diabetes but her cardiac status and her Hepatitis would each, in my view, contribute another 10 per cent to decreasing her likelihood of survival.

So whereas it would have been say 10 per cent, it might have gone to 20 per cent because of the presence of Hepatitis C and because of her cardiac failure, but that's not an exact science. I have discussed this with experts on pancreatitis and that was their kind of sense from hearing the situation, that that would be the kind of impact of these additional conditions on her survival.

7.161 However, he was not wholly comfortable with arithmetical or mathematical expressions in this context: it was more a multi-system failure and the accumulation of problems significantly increased the mortality risk. It was, he thought, more a matter of sense rather than modelling.[341] In a patient over 70 years of age, severe acute pancreatitis, quite apart from the patient's other diseases, carries a high mortality.

7.162 Dr Dunn discussed the possible connection between Mrs O'Hara's cardiac condition and the development of cirrhosis in view of the known connection in certain circumstances.[342] Cardiac cirrhosis rarely causes the classic cirrhotic pattern seen in primary liver disease. Mrs O'Hara's history was not consistent with such a connection. Dr Dunn's view was that her cardiac condition did not pre-dispose her in any significant way to the development of cirrhosis, though he did not exclude it entirely.[343]

Cause and date of Hepatitis C infection

The Hepatitis C antibody test of 5 November 1990

7.163 As noted in paragraph 7.116, tests for antibody to Hepatitis C were carried out on blood samples taken on 5 November 1990. The samples were reported to be negative after microbiological testing. If that was a true reflection of Mrs O'Hara's condition - a truly negative test - it is highly unlikely that she acquired Hepatitis C virus infection prior to November 1990.

7.164 In retrospect, however, having regard to the progression of Mrs O'Hara's Hepatitis C-related liver disease, it is now clear that the negative test result was a false negative. In Dr Mutimer's view that was almost certainly the case: Hepatitis C infection was established and had already caused cirrhosis at this stage.[344] As a matter of probability there is no reason to doubt that the result was a false negative.

7.165 The reliability of the test was explored with Dr Sheila Cameron of the West of Scotland Specialist Virology Centre, one of those who carried out the test (and signed the report of the results on 18 December 1990).[345] In her written statement, she commented that the test would have been carried out using the Ortho first-generation ELISA:

This was the first HCV antibody test. It was introduced in 1989 and was of limited sensitivity and specificity, ie there were false positives and false negatives. No confirmation test was available in our laboratory at that time. I would not exclude HCV infection on the basis of this result. There is a wealth of published data which supports this view.[346]

7.166 The weight of evidence before the Inquiry indicated that there were problems with the sensitivity of this test. The test results were frequently wrong in Scotland: early work carried out in Glasgow on anti-Hepatitis C virus testing by Dr Dow and others showed a significant proportion of false negative results. A likely explanation is that the tests were developed and validated using North American blood and that the predominant strain (genotype) of the Hepatitis C virus in North America was different from the predominant genotypes in Scotland.[347] So far as appears from the information available to the Inquiry, Mrs O'Hara's Hepatitis C was never genotyped.[348] It is possible, but highly speculative, that this explains the negative result in November 1990. Whatever the explanation, however, it is appropriate to dismiss the test result as a factor bearing on the date of infection.

The cause of Mrs O'Hara's Hepatitis C infection

7.167 Having regard to the finding that the November 1990 result was a false negative, and bearing in mind Dr Mutimer's view that on clinical grounds Hepatitis C infection was already established by then, Mrs O'Hara was clearly infected with Hepatitis C some time before November 1990 and the cause of her infection has to be found before that date.

7.168 Specific blood tests for the presence of Hepatitis C infection were not available anywhere in June 1985, the date of her last transfusion prior to November 1990, and reliable screening tests would not become available in Scotland for some time thereafter. This was because the virus itself was not identified until 1988. Screening for Hepatitis C of blood intended for transfusion commenced in the UK in September 1991. Mrs O'Hara had therefore probably been exposed to unscreened blood on transfusion on four occasions by the date of the false negative test in November 1990.

7.169 There were two possibilities: blood transfusion or a nosocomial (hospital acquired) source not directly related to transfusion. Dr Mutimer explained:

[I]nfections can be acquired in hospital, it is not just from blood transfusion, and that includes Hepatitis C. So we see people who have acquired Hepatitis C without ever having received a transfusion but who have had complex and difficult medical problems over a long period of time. With them it is likely that they somehow come into contact with it in the hospital setting. So 'nosocomial' refers to that.

So the blood may have been the source of Hepatitis C infection, we can't be certain. It is most likely but, with so many and such complex past illnesses, the hospital setting, including the blood transfusion, is likely to have been the source of her infection.[349]

7.170 So far as nosocomial infection is concerned, Mrs O'Hara had been an orderly in Stobhill Hospital[350] and could have been infected in the course of her work there. She had also been exposed to a large number of procedures in hospital and Dr Mutimer thought that blood transfusion was a more likely cause of infection than some other mechanism. Of Mrs O'Hara's various transfusions, Dr Mutimer said:

[W]e don't know if she had a transfusion in 1963, and in 1963 the frequency of Hepatitis C in the blood donor pool was probably incredibly low, so I don't think it would have been 1963. We know that in [1985] she already had abnormal liver function tests and I suspect it was Hepatitis C. So perhaps the transfusions in 1985 and 1991 are unlikely, in that Hepatitis C was probably already present. Which means 72 and 79, and perhaps the risk then was proportional to the magnitude of the transfusion. So there was one unit in 1972 and two units in 1979. So perhaps Sherlock Holmes might decide on 1979.[351]

7.171 He thought that it was never going to be possible to know. Dr Dunn thought that the transfusions in 1972, 1979 and 1985 were possibilities[352] but Dr Mutimer's analysis was, on balance, more persuasive.

7.172 There is no acceptable evidence to suggest that she might have acquired the infection in any other way: nosocomial transmission remains as a possibility but is unsupported by any relevant facts. The probability is that Mrs O'Hara was infected by blood transfusion. Having regard to the volume of transfused blood, the transfusion in 1979 was the more likely of the two earlier events to have infected her.

Mrs O'Hara's management as a patient in 1990-91

The role of Gastroenterology

7.173 The final submissions on behalf of the patient interest core participants, including Mrs Kennedy, relative to Mrs O'Hara's management as a patient,[353] raise two questions that relate to this period:

  • Whether, following the negative Hepatitis C result in 1990, and against the background of findings of abnormal LFTs, Mrs O'Hara's liver condition should have continued to be monitored by Gastroenterology.
  • More specifically, whether consideration should have been given to further investigation once the second generation of HCV tests had become available in September 1991.

7.174 Expressed in this way, the questions are not very helpful. Together, they imply that Gastroenterology did not continue to monitor Mrs O'Hara after November 1990. As a specific issue, the second has no time reference and no reference to any context defined by Mrs O'Hara's medical treatment.

7.175 As the narrative at paragraphs 7.114-7.116 above shows, Dr Morris of the Gastroenterology Department at the GRI did continue to deal with Mrs O'Hara's management after November 1990. It appears to be clear that Dr Morris considered that Mrs O'Hara should be seen after that date. In November 1990 he arranged for tests to be carried out, with a view to bringing her back to the clinic to discuss the results. She attended his clinic on 17 December. An arrangement was made at or after that date for an appointment at the gastroenterology clinic on 11 March 1991. Mrs O'Hara did not attend. Mrs O'Hara's failure to attend the clinic is, as Dr MacKenzie suggested,[354] understandable given the intensive care she had been receiving and was continuing to receive at the GRI for her cardiac problems at the time. There is no criticism of Mrs O'Hara. From the medical records it is not possible to form a view of what happened after 11 March 1991 so far as further Gastroenterology clinic appointments are concerned. It is clear, however, that, notwithstanding the referral to the GRI Cardiology Department, the 1990 test results (including the Hepatitis C result reported on 18 December 1990) did not end the GRI Gastroenterology department's interest in Mrs O'Hara as a patient.

7.176 There is no basis in the written records for a view that the Hepatitis C test result was treated as definitive or that it was the sole or main basis on which diagnosis was reached by Dr Morris and Dr MacKenzie resulting in the referral to the GRI Cardiology. Dr Morris' view, in his report dated 5 November 1990, was that mild congestive cardiac failure did not explain Mrs O'Hara's splenomegaly and abnormal blood tests.[355] He instructed further tests against that background. The particular test finding that Mrs O'Hara was negative for Hepatitis C antibody had not been reported by 17 December 1990, the date of Dr Morris' referral letter to Dr Lorimer, in which he set out the reasons for considering that cardiac investigations were appropriate (particularly the echocardiogram which suggested worsening heart valve problems).[356]

7.177 Dr Mutimer agreed with Dr Morris' view that chronic mild congestive heart failure might not explain Mrs O'Hara's abnormal liver function tests. He gave additional explanations of his view. Her abnormal LFTs had been causing concern for several months, reflected in questioning about alcohol consumption. In addition, some of the clinical findings suggested significant liver damage: the tip of the spleen was palpable, a potentially significant abnormality which often implies the presence of cirrhosis.[357]

7.178 Having reviewed the records as a whole, Dr Mutimer's view was that, with the exception of the November 1990 blood test result, everything pointed to Hepatitis C infection.[358] However, he contrasted the state of knowledge of Hepatitis C in the early 1990s with current knowledge. At that time, most GPs and hospital clinicians would have had very little knowledge of Hepatitis C. He said:

I think people's familiarity with Hepatitis C in the early 90s was really quite poor. Remember, the virus was only discovered in 89. The first tests available in clinics in 1990. So a lot of our knowledge about Hepatitis C at that stage was fairly superficial .... Perhaps it is that first test in 1990 which has really thrown them off track, I think, and that was unfortunate because, you know, it was a very clever thing for the doctor to do in 1990, to say there has been transfusion. There is liver disease, is it Hepatitis C? And then unfortunately an erroneous result has thrown him off track, I think.[359]

7.179 It is possible that Dr MacKenzie and Dr Morris were thrown off the track, to some extent, by the negative test result. It is, however, reasonably clear that it was not the test result that interrupted their management of Mrs O'Hara's case. Dr Morris did not express a view that the result was reliable. There were unanswered questions, so far as he was concerned, in his approach to Mrs O'Hara's signs and symptoms. It cannot be said that he treated the result as definitive, given the investigations he instructed into the other signs and symptoms Mrs O'Hara had at the time.

7.180 In Dr Morris' letter to Dr Lorimer dated 17 December 1990, written on behalf of Dr MacKenzie, he referred to the echocardiogram showing 'moderate to severe mitral regurgitation and mild to moderate tricuspid regurgitation'.[360] It appears that the echocardiogram findings were a significant factor in the gastroenterologists' thinking at the time. Together with enlargement of the liver and spleen, and splenic vein dilatation, these appearances suggested to them that congestion secondary to primary cardiac abnormality was the most likely cause of Mrs O'Hara's abnormal liver function tests. That appears to have been a clinical judgement on the basis of the findings set out in his letter.

7.181 Mrs O'Hara was to turn out to have severe cardiac problems requiring attention. The decision to refer her to Dr Lorimer was clearly correct. Throughout most of 1991, Mrs O'Hara was treated intensively for her cardiac problems. Replacement of her mitral prosthesis was necessary. Preliminary investigations of her coronary arteries were required. The surgical procedure in October 1991 was successful.

7.182 The question can be posed whether reliance on the test results of November 1990 had a significant and adverse effect on Mrs O'Hara's management. There is no evidence that management decisions were taken on the basis of the test results. It is of course clear that, had a positive and accurate result been reported, it is likely that a management plan would have been developed that took account of that finding. Not least, it would have had an influence on surgical procedures in 1991, given the potential risk of accidental transmission from patient to staff. It would have been a positive indication that, following her cardiac care, Mrs O'Hara would have required active care by gastroenterologists. On the basis of his earlier comments, Dr Morris would have wished a biopsy, for example. It does not follow that the negative finding prevented further gastroenterological input: it did not, in fact, as the narrative of follow-up arrangements into early 1991 shows.

7.183 Dr Mutimer was asked about the absence of gastroenterological involvement in the period between 1990 and 1995.[361] Whilst he initially observed that Mrs O' Hara should have 'remained in their domain', he was not critical, in all the circumstances, of the fact that this did not happen. That view is accepted. Mrs O'Hara was in the care of the cardiac department and was regularly monitored in hospital.

Further investigation following introduction of second-generation anti-Hepatitis C tests

7.184 Against this background, it is appropriate to return to the core participants' second question: whether consideration should have been given to further investigation once the second generation of anti-Hepatitis C tests had become available in September 1991.

7.185 As discussed in Chapter 31, The Introduction of Screening of Donated Blood for HCV, in the period between the first anti-Hepatitis C test released for evaluation in November 1989 and September 1991, there were significant developments in technology relating to anti-Hepatitis C testing.[362] A pharmaceutical company, Ortho, intimated to Professor Cash, SNBTS, and Dr Gunson, NBTS, in November 1989, that their ELISA[363] had received an export permit from the US Food and Drug Administration that would allow the use of the test for diagnostic use. By December 1989, the West of Scotland BTS had arranged to receive Abbott Laboratories' test kits for evaluation. The lack of a confirmatory test at that time was a factor that contributed to delay in introducing the tests routinely. Ortho's first generation RIBA[364] confirmatory test was sent to the United Kingdom for evaluation in February 1990. The recipients included Dr Follett at Ruchill Hospital in Glasgow. Ortho's second generation ELISA, with improved sensitivity, was anticipated in a marketing announcement in October 1990 and at a scientific symposium in November 1990. The availability of second generation Ortho kits for evaluation was intimated to the Advisory Committee on the Virological Safety of Blood on 21 November 1990. By then Abbott had further developments in hand. Their test was launched on 6 December 1990. In Scotland, anti-Hepatitis C screening of blood donations was introduced generally on 1 September 1991.

7.186 The type of Hepatitis C test used in Mrs O'Hara's case is not identified in the hospital laboratory reports.[365] It was carried out at the GRI Microbiology Department on the instructions of Dr Morris and reported on 18 December 1990. Having regard to the chronology above, it appears highly likely that it used one or other of the less developed test systems then available. That was Dr Cameron's evidence: she informed the Inquiry in her letter that the test would have been the first generation Ortho test.[366] Lack of sensitivity and specificity had been material factors in delaying the introduction of the test systems for general use. Locally, Dr Dow and others had reported in December 1989 that the Ortho Hepatitis C ELISA kit then commercially available had an acceptable specificity but an apparent reduced sensitivity compared with the development model they had previously tested.[367]

7.187 Improvements in technology in the course of 1991, leading to the general adoption of anti-Hepatitis C screening of blood donations in September, might have been expected to persuade gastroenterologists, if confronted by a patient's continuing pattern of deranged LFTs, to have submitted blood for further virus serology testing.

7.188 However, Mrs O'Hara was not in the care of the gastroenterologists at the material time and there was nothing to trigger a reference by the cardiac surgeons back to gastroenterology when her cardiac treatment was completed. It is recorded that, on her discharge from hospital in October 1991, following her heart valve replacement, her LFTs were normal. Consideration could only have been given to further investigations following the availability of second-generation anti-Hepatitis C tests if there had been in place mechanisms (which were never defined in the evidence) to secure the continuing involvement of relevant specialists in her care and management. There is no basis in the evidence before the Inquiry for a need, separate from arrangements for Mrs O'Hara's management while in gastroenterology care, to give consideration to further investigation related to the particular development of second-generation tests.

7.189 So far as the evidence discloses, there was no mechanism by which a former patient could be identified by a hospital following on a scientific development that might have a bearing on the patient's care or treatment and, on the initiative of the hospital, brought in for further investigation. Having regard to the obvious impracticability of implementing such an arrangement, it would not be appropriate for the Inquiry to make any recommendation that such a mechanism should be introduced.

Mrs O'Hara's management to late 1995

7.190 When admitted to the GRI on 25 February 1991, Mrs O'Hara had cardiac issues and she also had increased hepatomegaly, suggesting progressive enlargement of the liver, and her liver was slightly tender. In Dr Mutimer's view, these findings were not of themselves necessarily indicative of developing liver disease. At that stage, her cardiac problem could have caused congestion of the liver and could have contributed to her enlarged tender liver or the enlargement of her liver could have represented intrinsic liver disease, now known to be due to the inflammation of Hepatitis C.[368]

7.191 Mrs O'Hara required cardiac care in the first half of 1991. As noted above, there is no basis for criticism of the decision to refer her to the cardiac clinic at that time. If there is a problem, it arises from the fact that there was no engagement of the gastroenterologists in her management after March 1991. The substantive issue focused in the first question[369] is whether, in light of what was known at the time, and what developed during and after cardiac care, it was appropriate for her management to proceed without further advice from gastroenterologists after 1990 and, specifically, whether it was for gastroenterology to take the initiative and call her for review.

7.192 This issue has to be considered against the background of what was generally a good standard of management at the time. Dr Mutimer was asked whether, having regard to the medical records, there was 'someone missing from the team' from 1990, such as a gastroenterologist or a liver specialist.[370] The underlying concern was whether Mrs O'Hara's care might have been inadequate up to May 1995. He said:

She has got a good diabetic specialist and a good cardiologist, I think. They are probably very well trained physicians in the early 90s. They probably have very good background training in general medicine, including gastroenterology. So I don't have any reason to criticise any of the doctors who have been involved with her care so far ... It has taken a long time to get to the right diagnosis and to say what the stage of the disease is.

[T]here have been a number of doctors at a number of hospitals who have been involved and eventually they have got there ....[371]

7.193 He commented further:

[I] think again, if there had been no background cardiac problems, this probably would have come to a correct diagnosis much more quickly but this lady has been distracted by the need for, really quite major cardiac surgery, and it has also muddied the thinking about the cause of her abnormal liver function tests. So I can understand the delays that we see in establishing the correct diagnosis. It could have been diagnosed more quickly but I can understand why it took as long as it did.[372]

7.194 Until 1994 Mrs O'Hara reported no problems relevant to possible liver disease at annual review. It was in August 1994 that the condition of her liver again came to the fore.

7.195 As noted above, Mrs O'Hara frequently attended her GP in 1991, 1992, 1993 and 1994. On 17 June 1994 a diabetic assessment was noted as required and a blood test was taken.[373] The first LFTs noted in the GP records were reported on 9 February 1995 and were then normal.[374] No entry in the GP records raised an issue about Mrs O'Hara's liver or suggested a need for referral to gastroenterology.

7.196 Given Dr Mutimer's opinion of the position at 25 February 1991, it cannot be said that the views expressed in Dr Morris' letter of 5 November 1990 were untenable.[375] Dr Mutimer's evidence was careful and balanced and it was not contradicted or qualified by any other evidence. Mrs O'Hara was a difficult case, given her history and the range of symptoms and signs presented. In retrospect, and in the light of Dr Mutimer's evidence, it is unfortunate that Mrs O' Hara was not monitored by gastroenterologists between early 1991 and July 1995. Had such monitoring occurred the progression in her liver disease might have been identified.

7.197 Leaving aside the possibility that a different course of management might have been followed, there is a question whether Mrs O'Hara's Hepatitis C might have been diagnosed earlier in the course of her cardiac care. In Dr Mutimer's view, she was a patient with abnormal liver function and a patient who probably had significant liver disease.[376] As stated in his letter of 5 November 1990, Dr Morris thought that her cardiac problems did not entirely explain her liver problems. Liver disease was not investigated further, however, until she was referred back to the diabetic day unit at Stobhill in August 1994.

7.198 By that time, there had been a number of specialists involved in her care, and the focus since 1991 had been on her cardiac problems. Dr Mutimer thought that the hepatosplenomegaly noted in August 1994 was not, as the consultant physician at the time thought, possibly secondary to her mitral valve replacement. It was, he considered, much more likely that this showed liver damage.[377] He thought that there had possibly been some crossing of wires and that perhaps investigations that had been performed previously had gone out of focus.[378] Once Mrs O'Hara's heart was in good condition, however, people began to pay more attention to the enlargement of the liver and spleen. Matters began to develop thereafter.

7.199 In the circumstances that developed in 1994 and 1995, it is likely that the cardiologists would be looking for a cause of the enlargement of the liver and spleen other than her cardiac surgery. Dr Mutimer said:

I think in 1994 it is two or three years after she had a successful valve replacement? So I would be surprised if the cardiologist would accept responsibility for the enlargement of the liver and spleen. And I think it is much more likely that this is showing disease of the liver and then the enlargement of the spleen is almost certainly due to that. So it all points to the likely presence of cirrhosis at this stage, with portal hypertension, in other words pressure building up behind the liver, and that includes enlargement of the spleen.[379]

7.200 It appears that particular interest in Mrs O'Hara's problem among members of the GRI's cardiac team may have been generated by Dr McLaren's letter of 5 August 1994.[380]

7.201 Dr Mutimer thought that the management plan developed after review at Stobhill cardiology clinic in March 1995 was entirely acceptable at that stage.[381] However, the investigation did not run smoothly. As noted above in paragraph 7.126, significant hepatosplenomegaly and, in particular, splenomegaly were found but, in his letter dated 12 May 1995, Dr Dunn suggested that the condition of her lymph nodes might have a malignant source, for example lymphoma. Dr Mutimer thought that this reflected lack of knowledge of underlying clinical details: this was simply a case of cirrhosis due to Hepatitis C. Lymphoma was a possibility, but not likely[382] and it proved to be a false trail.

Dr Forrest

7.202 A new phase in Mrs O'Hara's treatment began with her referral to Dr Forrest. His response to the referral is set out at paragraph 7.136. Dr Forrest's report of 3 November 1995, based on her care records, noted hepatosplenomegaly from 1990 and biopsy evidence of established cirrhosis.[383] It commented on possible alternative aetiologies and it commented on the possibilities of treatment at the Royal and the Western Infirmaries, Glasgow, if the cirrhosis was due to Hepatitis C. He was not committed to a view that Mrs O'Hara's cirrhosis was due to Hepatitis C and doubted whether she was a candidate for Interferon treatment. He said he would arrange to review her liver biopsy. He was asked for further advice in March 1996 and reminded of that request in May 1996. On 10 July 1996, he reported his view that Mrs O'Hara probably had cirrhosis and a very mild continuing hepatitis.[384] He estimated the prospects of success with Interferon at 20-25% after prolonged treatment. He indicated that he was prepared to refer Mrs O'Hara to gastroenterologists at the Glasgow Western Infirmary for consideration of the then-new treatment with Interferon, which he described in his letter as having been funded on a 'limited basis'. He had still not seen Mrs O'Hara.

7.203 Dr Mutimer commented:

There is an elephant in the room, isn't there? So I would have thought it is all due to Hepatitis C, really. I'm not sure why he is suggesting that Hepatitis C is present but not responsible for the damage. That's not likely.[385]

7.204 Dr Mutimer's criticism of Dr Forrest's observations is accepted. Dr Mutimer considered that the link between Mrs O'Hara's symptoms and her Hepatitis C infection ought to have been obvious. The other possible explanations canvassed were not.

7.205 Dr Mutimer was broadly supportive of the line taken by Dr Forrest at this time relative to treatment, however.[386] He thought that Dr Forrest's estimates of possible success with Interferon, an estimated success rate of 25% overall, were optimistic, both generally and in the context of the treatment of patients with advanced liver disease. He did not think that data would have existed in 1995 for Dr Forrest to have made a more accurate estimate.[387] Mrs O'Hara had low prospects of a good outcome from treatment. She would not have been treated by Dr Forrest, however. Concentration of Interferon treatment in particular centres was common at the time and that was not surprising.[388] The drugs were expensive and there was a policy of restricting their use to a limited number of centres.[389] Mrs O'Hara would have been referred to Dr Morris, who had by then been appointed as a consultant and was running the treatment service.[390] In retrospect, Dr Mutimer thought that Mrs O'Hara was probably lucky that she did not have Interferon treatment: he suspected that she would have had a lot of side-effects and no success from the treatment.[391] Cardiac disease was probably also a counter-indication to Interferon treatment.[392] Review of the biopsy was an appropriate step, to satisfy the gastroenterologist that he agreed with the pathologist's views.[393]

7.206 Mrs O'Hara's daughter, Ms Annette McDonald, was a nurse at Stobhill. She asked for further information for Mrs O'Hara, probably during or shortly after her admission for liver biopsy in June or July 1995.[394] A doctor saw Mrs O'Hara with Ms McDonald and they were told that Mrs O'Hara had Hepatitis C as well as cirrhosis.[395] The family knew that when cirrhosis was established it was possibly too late to do anything.[396]

7.207 Dr Forrest had an opportunity to see Mrs O'Hara at this time; he did not do so. Another opportunity arose in July 1996 when he again reviewed her case; again he did not do so. Dr Mutimer was critical of Dr Forrest for carrying out only a 'desk-top' review of Mrs O'Hara's case in July 1996. The planned management that was developed was appropriate but Dr Mutimer thought that what might be missing was the chance to actually see the patient and to discuss her illness and the reasons why treatment was not suitable.[397]

7.208 It also deprived Dr Forrest of the advantages that might reasonably have been expected to accrue from direct contact with the patient to discuss her history.

7.209 Dr Mutimer's opinion that it would have been good practice for Dr Forrest to have seen Mrs O'Hara was clearly correct. Any patient would have benefited from an explanation of his or her condition and of why the forms of treatment that were available at the time were not suitable or were unlikely to be effective in his or her case. Given Mrs O'Hara's interest in obtaining explanations and information, this was not a case in which it might have been thought that there would be a disinclination to have the true position spelled out. She was, as were her daughters, 'mining' for more information about the implications for Mrs O'Hara of her infection.[398]

7.210 Dr Forrest's reports do not appear to have been copied to Mrs O'Hara's GP. He did not, therefore, make provision for informed discussions between Mrs O'Hara and her GP. However, at this time patients would have been dependent on specialist knowledge of Hepatitis C: it was not a subject that most GPs would have known about.[399]

7.211 Dr Forrest died on 26 June 2010, and it was not possible to have his observations on this chapter of evidence.

Counselling and information

7.212 A further issue raised by Mrs O'Hara's case relates to the failure to provide appropriate counselling and support for her Hepatitis C and its consequences after the diagnosis had been made in the summer of 1995. A particular complaint is that Mrs O'Hara was not told about the danger of secondary infection and appropriate precautions.[400]

7.213 In the context of the look-back exercise begun in April 1995, a document entitled Transfusion-transmitted Hepatitis C: Guidelines for Counselling Patients was widely available to those engaged in tracing recipients of blood or blood components from donors known to be carriers of the Hepatitis C virus.[401] The purpose of look-back, discussed in more detail in Chapter 35, An Investigation into the Steps Taken to Identify the Individuals Who Were Infected (Look-Back) was to trace NHS patients who had received blood, blood components or blood products derived from donations by donors who tested positive for Hepatitis C antibodies after 1 September 1991, when screening was introduced, and who had previously donated blood which was found by retrospective testing also to have been infective. The document provided background information on transfusion-transmitted Hepatitis C infection, the discovery of the virus and the development of tests for it. Among the modes of transmission highlighted were: sharing needles during intravenous drug misuse; transfusion; tattooing and other skin-piercing procedures; and, to a limited degree, sexual transmission. Hepatitis C positive individuals were advised that they should not donate blood. They should not share toothbrushes or razors and they should inform dentists and doctors of their HCV status. Information was given about Alpha Interferon, the only licensed therapy for chronic Hepatitis C at the time. The document was not intended for patient use but it provided one measure of what might reasonably have been expected in counselling an infected individual at the time Mrs O'Hara was told that she had Hepatitis C and cirrhosis in the summer of 1995. She was never counselled along the lines of the document.[402]

7.214 Mrs O'Hara was a person with clearly expressed concerns about her health and an anxious wish to have any treatment that was available. She found having Hepatitis C very difficult. Some of her concerns were created unnecessarily by inadequate and inaccurate information.

7.215 Mrs Kennedy said they were all shocked when a doctor at Stobhill said that blood had been taken from American prisoners and that this might be a source of Hepatitis C.[403] This was a misapprehension on the part of the person who gave the information. The Inquiry has seen evidence that some commercial large-pool Factor VIII blood products imported into the UK in the 1970s and 1980s were manufactured from plasma that included donations from prisoners. No whole blood used for transfusion in Scotland was collected outwith Scotland, however. The infected blood in Mrs O'Hara's case was donated in Scotland.

7.216 Other misapprehensions are less easy to deal with. Mrs Kennedy said that her mother hated having 'Hep C risk' stamped on the front of her medical notes and was embarrassed. She knew that Hepatitis C was an infection usually associated with drug addicts. She was well known in Stobhill, having worked there, and was worried that people might find out. She felt that the comment should have been concealed inside her notes.[404] However, none of the Stobhill records the Inquiry has recovered are so stamped and the two volumes of GP records both have the 'Special Hazards' section on the front page left blank. Certain sheets within the GP records are headed 'Hep C Risk'. The basis for apprehension that people in Stobhill might find out about her infection cannot be verified, although it was clearly real for Mrs O'Hara.

7.217 Mrs O'Hara's other daughter, Ms Annette McDonald, asked for further information for her mother, probably in June or July 1995. The doctor who saw Mrs O'Hara with Ms McDonald said that Hepatitis C had possibly caused cirrhosis of the liver and that she had probably contracted Hepatitis C from a blood transfusion. Their impression at the time was that the doctor played down the significance of Hepatitis C and implied that it was a common infection: cirrhosis was a lot more serious.[405] No advice was given about avoiding transmission or about her blood.[406] There was no offer of counselling or further information.[407] Mrs O'Hara asked about possible treatment for Hepatitis C. She was told there was no treatment as she already had cirrhosis.[408] Mrs Kennedy said:

[I] think when you have been attending hospitals, you do ask about treatments because it has been your experience that usually something can be done, you know, when you have had heart problems. So we just wondered, and I know my mum wondered, if just anything could be done because she was very used to following doctor's instructions and she was very faithful to doctor's instructions, and I think she just thought if there was something she could do things might get a wee bit better.[409]

7.218 In April 1998, Mrs O'Hara again asked about Interferon treatment, based on her reading of media reports.[410] The haematologist who saw her on 20 April left it to her GP to decide whether to re-refer her to the gastroenterologists. There is no record of her having been re-referred for gastroenterological opinion at this time.[411] The issues raised by her care down to mid-1997 were not resolved.

7.219 Except in relation to counselling relating to Mrs O'Hara's cirrhosis and the treatments that might have been available for it in her case, the complaints of Mrs O'Hara's family do not lend themselves to easy categorisation. The casual mis-information provided by an unidentified doctor about the source of blood would clearly have upset the family - but it had, and could have had, nothing to do with Mrs O'Hara's treatment. Her concern about entries in her Stobhill records referring to 'Hep C risk' would again be completely understandable given her long association with the hospital but the apprehension was not well founded in fact: the hospital records were not so marked.

7.220 Once Mrs O'Hara's cirrhosis was diagnosed, the appropriate source of accurate information about her condition, its prognosis, and counselling in relation to any particular treatment was Dr Forrest, the Consultant Gastroenterologist to whom her case was referred in September 1998. He had the opportunity to provide both information and counselling, either directly to Mrs O'Hara or by copying his inter-departmental letters to the GP for the benefit of Mrs O'Hara. Generally, there was the model of the look-back guidance as a source of what was required for the benefit of the patient.

7.221 It has been submitted that the treatment of Mrs O'Hara raises a systemic issue about the provision of counselling and support of patients with Hepatitis C. That there were deficiencies in her case is clear but there is no basis in the evidence as a whole for a view that these were due to any systemic failure. There were lapses attributable to an individual, Dr Forrest, but it cannot be found on that basis that there was a fundamental defect in the hospital's general procedures. Mrs O'Hara's case, while of great importance to her family, is not evidence of a universal or general failure on the part of the hospitals involved, nor on the part of the NHS as a whole.

Other issues

7.222 The SNBTS was not able to trace the donors whose blood was transfused during Mrs O'Hara's surgery in June 1985.[412] The GRI Blood Bank utilised an Apple computerised system from 1981-86. It has been explained that the Apple system could not accept the SNBTS donation number configuration. The GRI laboratory allocated an identifier that was entered into the Apple system and those records contained no cross-references to the SNBTS pack numbers. A paper record was kept of the respective numbers but the paper records for 1985-86 were destroyed in error during a laboratory move in 1995.[413] There are no extant records that would link the units used in Mrs O'Hara's case with the SNBTS unit numbers.[414]

7.223 The destruction of the paper record does not, of itself, raise any systemic issue for the Inquiry. Accidents occur in any system and may or may not indicate structural deficiency. Dependence on a paper record as a necessary link in the recording may be a different matter.

7.224 While it is understandable that the limitations of a particular computer system might prevent it from accommodating, or reading automatically, an electronic number configuration generated by a different system, it is less understandable that the text of a GRI laboratory record should not contain, by such means as the computer software allowed, the link number to the SNBTS source material.[415] If that was not possible at that time, reliance on a paper record inevitably meant those records were vulnerable to accidental or erroneous destruction.

7.225 The circumstances of the 'unfortunate' error have not been explained other than that it related to a laboratory move in 1995. Carefully specified protocols for the retention and destruction of records relating to patient care are a fundamental pre-requisite of sound administration of the NHS. Whether such protocols were in place and whether they were applied remain unanswered questions. Allowing two separate numbering systems in the principal records of interdependent NHS organisations, with linkage depending on paper records, questionable in itself, gives added weight to the requirement for controls.

Reasonable precautions whereby Mrs O'Hara's death might have been avoided

7.226 It was not suggested in the closing written submissions by the patient interest core participants that there were any reasonable precautions that might have been taken by which Mrs O'Hara's death might have been avoided.[416] There were none.

Cause of death

7.227 The cause of Mrs O'Hara's death was acute pancreatitis complicated by sepsis and multi-organ failure. Possible contributory causes were:

  • Hepatitis C virus cirrhosis consequent on blood transfusion prior to 1985.
  • Chronic heart failure with prosthetic mitral valve consequent upon rheumatic fever in childhood.
  • Type II diabetes.

7.228 The failure to record Hepatitis C as a cause of death was an error but, in the overall complex circumstances of her death, not an important error. It has been submitted that this reflects a systemic defect in procedure. While there are indications elsewhere of disinclination on the part of some doctors, and some families, to have Hepatitis C recorded (as occurred also in the case of HIV/AIDS) there is no evidence that the failure in this case was attributable to any policy or widespread practice.


7.229 Infection with Hepatitis C and progression of disease:

(i) While nosocomial transmission of the Hepatitis C virus cannot be excluded absolutely, it is highly likely that Mrs O'Hara was infected by blood transfusion.

(ii) The most likely date of infection was 28 November 1979 when Mrs O'Hara received a transfusion in the course of a hysterectomy.

(iii) Mrs O'Hara was tested for Hepatitis C infection by first-generation Ortho ELISA on 5 November 1990, with negative result.

(iv) The test result was a false negative.

(v) Mrs O'Hara developed cirrhosis due to infection with the Hepatitis C virus.

(vi) Insofar as Hepatitis C contributed to her death (and the extent of that contribution cannot be resolved with any confidence) her infection with the virus in 1979 could not have been prevented.

(vii) The failure to record Hepatitis C as a cause of death was an error but, within the context of the complex circumstances of Mrs O'Hara's death, not an important error. It was not found to be a systemic defect in procedure.

7.230 Mrs O'Hara's management as a patient:

(viii) It is impossible to form a view on the evidence as a whole that there was reliance on the test results relating to the blood samples taken in November 1990 which had or may have had a significant and adverse effect on Mrs O'Hara's management in 1990-91.

(ix) Mrs O'Hara had a complex medical history and, in particular, in 1990-91 had serious heart disease that warranted surgery.

(x) The gastroenterologists in charge of Mrs O'Hara's care at the end of 1990 referred her to the GRI Cardiology.

(xi) That decision was well founded, given their findings on examination and investigation. The diagnosis of congestive cardiac failure was sustainable.

(xii) The actions of the gastroenterologists, and in particular Dr Morris, including arranging a follow-up appointment for early 1991, suggest that the test results were not treated as definitive at the end of 1990 and in early 1991.

(xiii) Continuing gastroenterological supervision of Mrs O'Hara's case was interrupted in March 1991 when contact broke down.

(xiv) It is not possible to conclude, on the evidence as a whole, whether, if Mrs O'Hara had attended the appointment with gastroenterology on 11 March 1991, further examination by gastroenterologists would have changed the course of her management: that would be speculative.

(xv) Mrs O'Hara was receiving comprehensive cardiology care at the time and non-attendance was considered to be understandable. The records do not disclose follow-up at gastroenterology.

(xvi) When discharged from hospital in October 1991, Mrs O'Hara's liver function tests were normal.

(xvii) Having not attended gastroenterology in March 1991, Mrs O'Hara's liver condition was not monitored systematically between 1991 and 1994.

(xviii) Mrs O'Hara remained asymptomatic of anything to suggest chronic liver disease until August 1994 and her liver function tests were at least sometimes within her normal range. There was nothing to stimulate interest in her liver condition until Dr McLaren raised the issue in August 1994.

(xix) Since Mrs O'Hara was not receiving care related to liver disease between September 1991 and August 1994, and had not reported signs and symptoms giving rise to concern about her liver, there were no grounds for referring her for testing with second-generation anti-Hepatitis C tests when they became available.

7.231 Counselling and information

(xx) There was a significant lapse in Mrs O'Hara's management as a patient after she was referred to Dr Forrest on 11 September 1995.

(xxi) Dr Forrest's initial review letter dated 3 November 1995 is not criticised as unduly delayed but he carried out a review of records without seeing Mrs O'Hara.

(xxii) A request for further review was sent to Dr Forrest in March 1996. He responded on 10 July 1996, again without seeing Mrs O'Hara.

(xxiii) Taken together, these periods amounted to unacceptable delay on the part of Dr Forrest in responding to the referral and a failure in management attributable to his repeated 'desk-top' disposal of issues relating to Mrs O'Hara.

(xxiv) Mrs O'Hara should have had an opportunity to meet Dr Forrest and discuss her condition and the reasons for his opinion that Interferon treatment was not considered suitable in her case.

(xxv) Mrs O'Hara should have been given advice and counselling about her Hepatitis C status along the lines of the April 1995 document: Transfusion-transmitted Hepatitis C: Guidelines for Counselling Patients.

(xxvi) She did not receive any such counselling and advice. Dr Forrest was in a position to tender counselling and advice and should have seen Mrs O'Hara for that purpose.These deficiencies in Mrs O'Hara's management as a patient were attributable to Dr Forrest, stemming from his failure to see Mrs O'Hara in person, and did not evidence a universal or general failure on the part of the hospitals involved, nor on the part of the NHS as a whole.

Alexander Black Laing


7.232 Mr Laing was born on 7 December 1923. He died on 4 September 2003. The certified cause of death was 'Hepatitis C Related Liver Disease'.[417]

7.233 Mr and Mrs Laing were married in 1951. Mr Laing was, prior to retirement, a linesman with the North of Scotland Hydro Electric Board and its successors. He retired in 1985.[418] As with all of the deaths remitted for inquiry in Term of Reference 6, it is important to provide information that may help Mrs Laing and her family understand the background to Mr Laing's infection and ultimate death. On a more general level, however, his experience illustrates the natural history of Hepatitis C infection in a man who, at the time of infection, was older than others investigated. It is also an illustration of exemplary care.[419]

Mr Laing's medical history

Surgery in 1990

7.234 Mr Laing had surgery at the Aberdeen Royal Infirmary (ARI) on 7 August 1990. He was 66 at the time. The diagnosis was Duke's C carcinoma, indicating that the cancer had infiltrated through the bowel.[420] The tumour had moved beyond the local territory of the bowel and penetrated one of the seven lymph glands which were sampled at operation and examined microscopically. The fact that the cancer had penetrated one only of those lymph glands offered a slightly better prognosis than had it penetrated more than one. It was, nevertheless, a cancer with a poor prognosis in the longer term and a high chance of recurrence.[421] In the event, Mr Laing made a good recovery.[422]

7.235 In the course of surgery Mr Laing received blood transfusions. He received two units of whole blood and other blood components and products.[423] The transfusion of whole blood is relevant for the purposes of this Report as it was capable of transmitting Hepatitis C infection. At the end of a course of out-patient care following surgery, lasting some five years, Mr Laing was told that the cancer was clear but that he had contracted Hepatitis C infection from the blood transfusion.[424] Mr Laing had been identified as being at risk by the UK-wide look-back exercise into transfusion-related Hepatitis C virus (HCV) infection which was in progress in 1995.

Hepatitis C look-back

7.236 The purpose of look-back was to trace NHS patients who had received blood, blood components or blood products derived from donations by donors who tested positive for Hepatitis C antibodies after 1 September 1991, when screening was introduced, and who had previously donated blood which was found by retrospective testing also to have been infective. Formal written intimation that Mr Laing had been so identified was given in a letter from the Scottish National Blood Transfusion Service (SNBTS) to his GP dated 26 April 1995. Enclosed with the letter was a form for the assessment of Mr Laing's suitability for counselling. The form was completed by the GP on 28 April.[425] Procedures for managing the exercise had been developed on a national, UK-wide basis by a steering group of which Dr Graeme Alexander, Consultant Hepatologist, Addenbrookes NHS Trust, Cambridge, was chairman.[426]

7.237 The look-back exercise will be discussed in greater detail in Chapter 35, An Investigation into the Steps Taken to Identify the Individuals Who Were Infected (Look-Back). At this stage, it is sufficient to note parts of the wider context. In the South East of Scotland Blood Transfusion Service, a local exercise had demonstrated that look-back was feasible. Scottish Health Ministers were persuaded by December 1994 that there should be a look-back exercise for Scotland as a whole. In England and Wales, proposals for a look-back study began to be considered almost as soon as Hepatitis C testing showed that some blood donors tested positive. Dr Alexander's group had started working in 1992-93.[427] However, until December 1994 the proposal was controversial. Objections were overcome by the end of the year and look-back was commenced throughout the UK in 1995.

7.238 Dr Alexander said that the majority of Hepatitis C positive blood was donated by individuals who had, at some time in the past, used illegal drugs.[428] Over a long period, people with a history of intravenous drug use were asked not to give blood. Standard procedure at donation sessions before September 1991 included inspection of prospective donors for physical evidence of their having injected drugs. Drug use resulting in donor infection might have occurred many years earlier and been forgotten, however, or, in the absence of signs and symptoms of disease, may have been dismissed as irrelevant by the donor. Apart from physical inspection, investigation of the history of the prospective donor was inconsistent and seldom involved questioning in depth.[429] Practice improved in and after 1982 in response to the threat of AIDS but, as Dr Alexander's findings indicate, individuals with a history of intravenous drug use still made up the majority of those testing positive for Hepatitis C after September 1991.

7.239 Another cohort of infected donors acquired Hepatitis C infection from blood transfusion, again in some cases many years earlier. In 1991-92, when Hepatitis C screening of donated blood began, Dr Alexander and his colleagues were surprised at how many blood donors coming to sessions tested positive: they had not anticipated that quite as many people might have acquired Hepatitis C from transfusion.[430] The majority of individuals with Hepatitis C infection, whether acquired by injecting drugs or by transfusion, did not become ill at the time of infection with the virus. Whether knowingly or not, some people potentially infective with Hepatitis C continued to give blood.

7.240 At follow-up as part of the look-back exercise, it was ascertained that the donor in Mr Laing's case had received a blood transfusion around 20 years previously.[431] This was the only risk factor attributable to that particular donor. In his evidence, Professor Marc Turner, Medical Director of the SNBTS, outlined the approach to this risk factor. Deferral[432] of donors who had themselves received blood transfusion was not introduced in the UK until 2004. At that time, the SNBTS initiated deferral of donors who had received a blood donation since 1980. The measure was related to the risk of transmission of variant Creutzfeldt-Jakob disease (vCJD). The only other country of which Professor Turner was aware which defers donors permanently because they have themselves had a blood transfusion is France, where such a measure was introduced in 1997.[433]

Counselling and forward planning

7.241 After the UK national look-back programme was initiated, the focus was on previous blood donors returning to make donations. If found to be Hepatitis C positive on return, it was assumed that the donor might also have been positive at the time of donations made before screening had started.[434] Recipients of any earlier donations could then be identified and approached with a view to counselling and testing to determine their Hepatitis C status. In Scotland, if the patient's GP was willing to undertake that role, the SNBTS would provide details of the blood samples needed and where these should be sent, and also offer any further support or advice required. If, on the other hand, the GP wished the Blood Transfusion Service to notify and counsel the patient, the SNBTS was happy to do that. It was recognised that it might not be advisable to tell some patients and provision was made for that situation.[435]

7.242 Mr Laing's GP, Dr Lynch, elected to undertake his care in this regard and sought advice from the SNBTS.[436] On 31 May 1995, he was sent copies of the nationally agreed counselling guidelines and a form to report the outcome of the process.[437] Dr Lynch wrote to Mr Laing on 6 June 1995 inviting him to make an appointment.[438] On 27 June he again asked Mr Laing to call as the results of the blood tests had been received.[439] Dr Lynch saw Mr Laing and told him the outcome. He then wrote to Dr Yates, consultant at the North East Scotland Blood Transfusion Centre at the ARI, noting that the Hepatitis C antibody and confirmatory tests were positive, providing current liver function test results, which were abnormal, and noting:

I have told him that he seems to have contracted Hepatitis C from his transfusion 5 years ago and that it may or may not damage his liver and that he will be seeing a Specialist to advise about the possibility of Interferon or not. He accepts all this with equanimity.[440]

7.243 Dr Alexander considered that a fair forward plan had been established.[441] Mr Laing was referred for hospital care at the gastrointestinal clinic.[442] His general health was reported to be perfect and he was said not to have hepatomegaly (enlargement of the liver). He was seen quite promptly in July 1995 and examinations were carried out on 15 August and reported to his GP. At that stage, Mr Laing was thought to have an asymptomatic infection with Hepatitis C attributed to the blood transfusion in 1990. He was not jaundiced and had no other stigmata (signs) of liver disease. Liver function tests were repeated and a PCR (polymerase chain reaction) test performed to confirm that he was still harbouring the virus. The history of Duke's C carcinoma was thought to be a problem and further tests were instructed[443] as it appears to have been thought that cancer might have recurred.[444] It was thought that Interferon therapy might be of no use to him.[445] In retrospect, Dr Alexander thought that the reasoning about cancer was suspect but that the right decision had nonetheless been reached about treatment.[446] In 1995 clinicians did not have good insight into the natural history of Hepatitis C, particularly in the older age group of patients. The evidence at that time suggested that there was a 10-20 year lag before cirrhosis would be established.[447]

Hepatitis C infection in older patients

7.244 Dr Alexander explained that the contemporaneous assumption about progression to cirrhosis was now known to be wrong in the case of older patients.[448] The common assumption in 1995 was reflected in the report by Dr Sinclair, Consultant Gastroenterologist, sent to Dr Lynch on 17 November 1995:

We now know that the long term outlook with hepatitis C is probably, in someone of this age group, fairly benign as it would probably be a significant amount of time before he produced enough chronic liver damage to creat [sic] ill health and my guess is that he will die of something other than liver disease. He is completely unphased [sic] by the whole thing but I do think we are due him a clearcut opinion as to the state of his liver and the only way to do this is with liver biopsy.[449]

7.245 Dr Alexander thought that recurrence of cancer in the longer term was more likely than not, with a related risk of mortality.[450] At the time, however, there was no evidence of metastasis from the Duke's C carcinoma.[451] A liver biopsy was carried out on 25 January 1996 which showed chronic active hepatitis and gave rise to a suspicion of cirrhosis.[452] The tissue sample extracted on biopsy was fragmented, which may happen when the liver has significant scarring. In such cases only softer tissue comes out with the needle; scar tissue is not withdrawn with the core. The findings were therefore not absolutely reliable. Dr Alexander interpreted the pathologist's comments as reflecting suspicion that there was cirrhosis, masked by the state of the core sample withdrawn.[453] That impression was strengthened by the degree of liver inflammation noted. Dr Alexander thought that Mr Laing probably had cirrhosis in 1996.[454]

Clinical management

7.246 Mr Laing's management was discussed on 2 May 1996 at a clinico-pathological conference attended, as was typical, by the clinicians involved in the patient's care and the hospital pathologists.[455] That was good practice. There might be one or two or maybe up to a dozen people at such a conference. Dr Alexander speculated that there would have been a discussion suggesting that the pathologist's views were guesswork, that Mr Laing was very well, that he did not have any signs of liver disease and that there was nothing clinical to suggest cirrhosis.[456] It cannot be concluded that this did happen but the outcome was consistent with the hypothesis.

7.247 The overall conclusion was that the patient did not have cirrhosis. The consensus that emerged was that the biopsy showed mild inflammation affecting the liver with some early fibrosis which was a different conclusion from that of the pathologist.[457] Dr Alexander thought that this slightly underestimated the condition.[458] He questioned the approach: he had always worked on the assumption that one took the worst possible news when making clinical decisions rather than the best possible news. If the pathologist was suspicious that it was cirrhosis, it was reasonable to follow his view. Others, however, worked in different ways.[459] Dr Alexander thought that the pathologist's report was quite clear that there were features of cirrhosis but that it would have made no difference at all to Mr Laing's clinical management had the pathologist's view prevailed.[460]

7.248 Among clinicians at this time there was no enthusiasm for therapy, given Mr Laing's age, the absence of symptoms of Hepatitis C and his mildly abnormal liver function test results.[461] Later, in September 1996, it was thought that there might be a case for Interferon treatment and that was discussed with Mr Laing. Mr Laing's preference was to 'take his chances' and not to have treatment. Dr Lynch was asked to keep an eye on his liver function tests.[462] As at September 1996, Dr Alexander's data over a 10 year period showed a success rate with Interferon of less than nine per cent across the board. When the position was reviewed in about 2000-01, it was found that people over 60 did not respond at all. In addition to questions about its effectiveness, the treatment was unpleasant to administer. Dr Alexander thought that Mr Laing and his doctors had taken the right decision: on balance, Mr Laing had little to gain and a lot to lose by being treated.[463]

7.249 Monitoring continued and regular blood tests were taken. Mr Laing was told that there was little that could be done for the infection and that such treatment as there was might make him worse. In Mrs Laing's words, he 'just got on with his life' but he was careful to protect his family. If he had a cut, he would warn family members to keep clear of the blood.[464]

7.250 There was an unfortunate incident in September 2000 when Mr Laing needed some dental treatment and his own dentist refused to treat him because he was Hepatitis C positive.[465] Dr Alexander said that incidents of this kind happened all too often.[466] Some dentists were apprehensive that liver disease pre-disposed the patient to bleeding but there was no reference to clotting problems in the record and Dr Alexander could not assume that the dentist had made his decision on concerns about bleeding rather than a more general fear of infection transmission.[467]

The return to ill health

7.251 In about 2000, Mr Laing began to become tired. His appetite was poor and he developed a tremor in both hands. He slept a lot and gave up bowling.[468]

7.252 In December 2001, he attended the ARI complaining of anorexia, lower abdominal and back pain, insomnia, dark urine and light stools over a period of two to three weeks. He was admitted to hospital between 8 and 11 December. Mr Laing's liver function test results were deranged. An abdominal ultrasound scan failed to reveal any relevant abnormalities, in particular in the liver. It was decided that he had had gallstones that had passed.[469] Nevertheless, on 31 December he was referred to the surgical out-patient department for surgical assessment on the view that gallstone disease was the underlying problem.[470] Dr Alexander thought that the blood tests and ultrasound results were not consistent with that diagnosis. In reaching the decision that the underlying problem was an early manifestation of liver failure, he was not influenced by the fact that no gallstones were noted in the gall bladder as they could have been missed. Rather, there was nothing to suggest that gallstones were the cause of the symptoms or the likely cause of Mr Laing's problems. The symptoms were more likely to be an early manifestation of liver failure due to Hepatitis C.[471]

7.253 In addition to gallstones, the reference letter to the ARI of 31 December 2001 referred to Mr Laing's chronic active Hepatitis C.[472] In January 2002, Mr Laing began vomiting again.[473] He was seen at hospital on several occasions in January, February and March.[474] Vomiting persisted. The department of Biochemistry and Haematology reported on 24 April 2002 that his biochemical metrics were consistent with hepatic impairment, repeating a report of 5 December 2001.[475]

7.254 On 19 November 2002, Mr Laing was referred to the breast clinic at the ARI for investigation of a swelling beneath his right nipple.[476] The GP was unsure of its significance. Right gynaecomastia (enlarged breast) was diagnosed. In a letter dated 18 February 2003, the consultant reported:

He does not appear to have any particular predisposing factors to gynaecomastia.

7.255 She noted that he had reported weight loss, loss of appetite and vomiting and suggested that he might be referred back to gastroenterology.[477]

7.256 Mr Laing was seen at the ARI Gastroenterology Clinic on 4 March 2003. The consultant's report of the examination to the GP stated:

He feels well with no nausea or vomiting. His breast pain has decreased. I note that he had a liver biopsy back in 1996, which suggested fibrosis and it is conceivable that he has now progressed to cirrhosis. It may be that the Gynaecomastia is associated with the cirrhosis. He has no abdominal or ankle swelling and feels well and therefore there is no indication for any further intervention at present.

7.257 He was to be reviewed in six months.[478]

Advanced liver disease

7.258 Early in June 2003, Mr Laing was so unwell he could not get out of bed to go to the toilet. He was vomiting, his abdomen was distended, his speech was slurred and he was dribbling from the mouth. Mr Laing was not a man to call the doctor but Mrs Laing did call for help.[479] The GP visited on 6 June and prescribed medication to settle his stomach and assist sleep. Mrs Laing contacted the GP again on 16 June.[480] Following examination, the GP referred him to gastroenterology at Woolmanhill Hospital, Aberdeen,[481] and it was arranged that he would be admitted there.[482] The referral letter on this occasion set out fully the GP's findings and Mr Laing's recent history; Mr Laing had gynaecomastia, thought to be due to his cirrhosis, weight loss, loss of appetite, nausea and vomiting. On examination the GP had found him to be jaundiced. He had tremor on both hands and his abdomen was distended. He had slight epigastric (abdominal) tenderness and was unsteady on his feet, among other signs and symptoms. There was a concern that his neurological symptoms of unsteadiness, including positive Romberg's sign and tremor, indicated some cerebellar dysfunction.[483] In the event, he was seen at the gastroenterology and liver service department at the ARI. It was reported by the clinic that he had no problems in relation to Hepatitis C and did not want to be treated.[484] His bloods were checked and it was noted that arrangements had been made for him to be seen at the clinic in six months.

7.259 Dr Alexander explained that the gynaecomastia was a sign of advanced liver disease caused by excess oestrogen changing the balance of hormones in circulation. In advanced liver disease more oestrogen circulates freely and more female characteristics develop.[485] In his view the picture was of advanced liver failure with hepatic encephalopathy (brain disorder caused by liver dysfunction) which characteristically comes with unsteadiness of gait and tremor.[486] Dr Alexander considered that many of the symptoms at that time would have been readily attributable to evolving liver disease.[487]

7.260 Mr Laing was seen at Woolmanhill Hospital on 2 July 2003 before being admitted to the ARI from 7 to 28 July 2003.[488] A Computerised Tomography (CT) scan was performed on 24 July.[489] Dr Alexander highlighted the significant findings from the scan. The liver was small. With most liver disorders the liver initially becomes enlarged and then, as the process evolves over years or even decades, the liver shrinks and eventually becomes too small to sustain life. In Mr Laing's case, the liver was also described as 'irregular', which meant that the surface of the liver had a scalloped contour consistent with cirrhosis. There was no focal lesion and so there was no sign of cancer. Dr Alexander was surprised that the spleen was not enlarged as it often is in advanced liver disease. Mr Laing also had moderate ascites, a collection of fluid in the abdomen, which was suggestive of liver failure and, from a clinical point of view, indicated that life expectancy was less than two years. On this occasion he had gallstones, which were missed previously on the ultrasound scan. These features told Dr Alexander that Mr Laing had advanced liver disease.[490]

7.261 Mr Laing was re-admitted to the ARI on 30 July but deteriorated rapidly.[491] There was a picture of steady decompensation: his condition was no longer under control.[492] Mr Laing now had signs that implied an increasing risk of serious disease and death including bleeding, ascites and confusion.[493] Mr Laing had also developed pedal oedema (swollen feet), another feature of liver disease.

7.262 Mr Laing was not able to go home and began to fade. A decision was taken that he should not be resuscitated and palliative measures were put in place. He died on 4 September 2003 with his family at his side.[494]

The natural history of Mr Laing's infection

7.263 The certified cause of death was 'Hepatitis C Related Liver Disease'.[495] Dr Alexander thought it should have been liver failure secondary to Hepatitis C and cirrhosis but that it was as accurate as it needed to be for the purpose of communicating the cause of death.[496]

7.264 Dr Alexander explained some of the mechanisms involved in Mr Laing's final illness. He had jaundice. Although the precise mechanism by which jaundice is caused is not very clear, essentially bilirubin (a bile pigment which is orange or yellow) is not cleared by the liver and is instead pumped back into the circulation resulting in what is known as a 'jaundiced appearance' (typically yellowish pigmentation of the skin and eyes). Jaundice was a sign of the liver's response to injury. Cachexia (wasting) occurred: in advanced liver disease the body starts to use its own store of fat and muscle as a source of energy rather than food and muscle bulk is lost. Mr Laing lost all fat and looked thin, a feature of very late disease. Portal hypertensive gastropathy occurred. Blood normally travels from the gut into the liver, a soft organ, under low pressure. If the liver becomes distorted and scarred it is hard for the blood to get from the gut into the liver. It starts to go backwards and seek other routes. The stomach, downstream of the pressure effect, becomes very distended, thickened with blood. The gut comes under high pressure and that makes it develop varices (varicose veins) which can bleed.[497]

7.265 Dr Alexander said that understanding of the natural history of Hepatitis C in older patients is no longer as it was initially thought. As now understood, an individual infected with Hepatitis C at nearly 67, as Mr Laing was, was likely to experience relatively rapid progression of disease. Most early experience was based on non-A, non-B Hepatitis (NANB Hepatitis) transfusion-related liver disease prior to the introduction of Hepatitis C testing. In those circumstances the majority of people died of diseases related to the reason for which they had been transfused, not to the hepatitis that arose as a result. As a result, there was an artificially skewed view of what NANB Hepatitis/Hepatitis C did to patients. It was not until the introduction of testing for Hepatitis C in 1991 that it was realised that many people had very different disease outcomes from that which had been previously described. The real picture was described about five or six years later.[498]

7.266 Dr Alexander had extensive research experience. His laboratory's work on the effect of ageing (measuring people's 'biological age') and outcome is discussed in Chapter 16, Knowledge of Viral Hepatitis 3 - 1986 Onwards, at paragraph 16.65. In short, physical changes in the structure of DNA as people grow older makes the DNA vulnerable to damage. The same mechanism affects Hepatitis C-positive patients, once they reach a certain biological age. If the patient does not have an effective immune system, they cannot cope with Hepatitis C so that the virus takes a stronger grip.[499] The immune system begins to be impaired generally when one gets to around 60; in an HCV- positive patient that process is accelerated and response to treatment is also affected. Dr Alexander's laboratory found that the biological age at which treatment was significantly less likely to be effective - the treatment cut-off age - was 58. Mr Laing's age is a particular indication that he would not have benefited from antiviral treatment.[500]

Source of infection

7.267 As discussed in paragraphs 7.235 and 7.240, it was clearly established that Mr Laing contracted Hepatitis C from the blood transfusion received at the time of his surgery for cancer in 1990. He died of the complications of that infection. At the time of his surgery in 1990, donated blood was not screened in the UK for Hepatitis C: screening was introduced in 1991. There was an issue for the Inquiry whether, had HCV screening been in place in Scotland, the donation that infected Mr Laing would have been identified and not used.

7.268 After HCV was identified in 1988, its genetic characteristics became the subject of intense research.[501] Variations in those characteristics were identified which were sufficient to define genetic sub-groups, or 'genotypes', which differ from others of the same virus, although not sufficiently to be considered different viruses. The genes of individual genotypes, like other organisms in the body, define their 'genomes'. The immune system responds to the activity of a virus by producing antibodies, proteins that seek to neutralise part of the virus. Antibodies remain in the body and, with appropriate technology, can often be identified. With modern, sophisticated technology, the genotype of the virus can be determined by scanning for particular antibodies to the virus.[502]

7.269 At the date of Mr Laing's surgery in 1990, early tests had been devised for screening donors' blood for HCV. The tests, known as enzyme-linked immunoabsorbent assays (ELISAs), were chemical products developed by pharmaceutical companies from components that would react with antibodies to HCV if they were present in a sample of serum, producing a change of colour.[503] More sensitive second-generation ELISA tests were used in screening blood donors from autumn 1991.

7.270 First-generation ELISAs targeted two specific areas of HCV that, as events were to prove, were characteristic of Genotype 1, which was particularly prevalent in the USA but were not present, so far as is material for present purposes, in Genotype 3 of the virus.[504] Technically, the first-generation tests were directed against the NS4 region of the virus, a non-structural region of the virus found in Genotype 1. So the components used for first-generation tests could detect only Genotype 1 efficiently. They did not detect many Genotype 2 or 3 cases at all well.[505]

7.271 In the result, the first-generation tests initially introduced for Hepatitis C screening of blood donations appeared relatively successful in identifying Hepatitis C-positive material in the USA but relatively unsuccessful in the UK where there was a high prevalence of Genotype 3 HCV.

7.272 It became of interest to identify the HCV genotype of the donor whose blood was transfused to Mr Laing. This was in order to determine whether the infection might have been detected and the donation deferred - that is withdrawn from use for transfusion - if routine screening of blood donations had been carried out at the time of Mr Laing's transfusion in August 1990.

7.273 The infected donation was traced through the national look-back process, as already noted. The donor had a blood transfusion in the 1960s or 1970s and may have acquired infection at that time, which was long before issues of testing for Hepatitis C became relevant.[506] A retained serum sample was found to be Hepatitis C-positive, using a second-generation ELISA test, on 8 January 1992. Research identified the genotype of the virus in question as Genotype 3.[507] Specifically, the donor genotype had high concentrations of four positive antibodies involved in the fight against Hepatitis C. Components of the second-generation tests targeted specific parts of the virus genome (components C22 and C33) found in Genotype 3.

7.274 In March 1992, as part of a research project in which Dr Brian Dow[508] was involved, the same sample of the donation was re-tested using the Abbott first-generation test which had been available at the time of the original donation in some Scottish virology laboratories. The sample tested negative for Hepatitis C.[509] If the donation had been tested at the time it was given and transfused to Mr Laing, the first-generation tests then available would have been negative. The blood would have been banked and used for clinical purposes, as it was in the event in the course of Mr Laing's surgery.[510]

Surrogate testing

7.275 Before the introduction of the first-generation ELISAs, blood could be screened using tests which were not directly related to Hepatitis C itself but used assays that might give an indication that the subject may have been infected with Hepatitis C. These are known as 'surrogate' tests.[511] They were not conclusive on the presence of HCV or its antibody but indicated signs associated with infection. Observation had shown that in patients who had Hepatitis C there was a high correlation with raised levels of alanine amino transferase (ALT), a liver enzyme. One surrogate test therefore targeted ALT levels. There was also a reasonable correlation between having Hepatitis C and also having the antibody to Hepatitis B core antigen (anti-HBc).[512] The other surrogate test accordingly targeted anti-HBc.

7.276 Within the same research project in 1992 referred to in paragraph 7.274 above, Dr Dow and his colleagues therefore looked at surrogate testing. They carried out anti-HBc testing and found that the sample from the donor involved in Mr Laing's case was one of those which was anti-HBc negative. Dr Dow concluded that the result would have been the same had the donation been tested at the time of donation.[513] Dr Dow's research project had investigated the ALT levels in 90 donations but the donation in question was not among those investigated for ALT.[514] Subsequently, however, Dr John Gillon, SNBTS, was able to access and follow up the records of the donor whose blood was implicated in Mr Laing's infection with Hepatitis C. The records showed that the donor's ALT level was tested on four occasions, in February and August 1992, in December 1993 and in October 1994. On each occasion the level was well within normal limits. Dr Dow concluded that it was likely that the implicated donation would have given a normal ALT value if the donor's blood had been tested in August 1990.[515]

7.277 The question whether ALT surrogate testing should have been introduced in Scotland in the period before introduction of the anti-HCV assay was extensively debated and is discussed at length in Chapter 27, Surrogate Testing of Donated Blood for non-A, non-B Hepatitis. In the circumstances, however, ALT testing of the donated blood would not have produced counter-indications to the use of the donation in Mr Laing's case.

7.278 It was submitted that Mr Laing's case raised systemic issues related to the use of blood from people who had received transfusions; about the non-introduction of surrogate testing in Scotland; and about the screening of donations.[516] There is no basis for the view that, given what was known in 1990, donors who had themselves received a donation should have been excluded from donating at that time. There are systemic issues for the Inquiry relating to the non-introduction of surrogate testing. However, the decisions, and the failures to reach decisions, that had the result that surrogate testing was not adopted in Scotland, could not have influenced Mr Laing's case. All of these issues are dealt with in Chapter 27, Surrogate Testing of Donated Blood for non-A, non-B Hepatitis. Similarly, had screening of blood donations been in place in the summer of 1990, the kits used would have been first-generation ELISAs and would not have detected Hepatitis C in the donation which subsequently infected Mr Laing. Mr Laing's death from complications of his infection with Hepatitis C, having survived serious and potentially fatal cancer, was a personal tragedy for Mrs Laing and her family. That is the light in which it should continue to be seen.

Mr Laing's treatment as a patient

7.279 Dr Alexander considered that Mr Laing's treatment had been exemplary.[517] In this case, the summary of his views in his report is the best expression of the position:

The short interval of just six years between acquisition of hepatitis C virus infection and documentation of cirrhosis at liver biopsy and the seven years that followed thereafter to his death, are consistent with what we now know about the natural history of hepatitis C virus infection. The proportion of patients that go on to develop cirrhosis and the rate at which cirrhosis develops subsequently are greatly accelerated in the elderly and in particular in men over 60. The fact that he had been overweight earlier in life may have been an additional confounding factor increasing his chance of becoming cirrhotic and increasing the rate at which the disease would progress. The first large publications drawing attention to the importance of age on the progression of liver fibrosis were published around 1997 and would have been discussed in abstract form, probably in the preceding few months. Thus the information that was provided to Mr Laing at the time of his biopsy in 1996 was probably 'best known practice'.

The fact that he was told that his disease was benign and was likely to remain so may well have influenced his decision not to accept the offer of anti viral therapy and it seems clear to me from the letters around that time that he was likely to have been told that the Interferon-α treatment was not likely to offer him a cure. I agree that was certainly true at the time and the response rate to treatment with Interferon-α in our centre was just 9% of cases ... with an even lower rate in the elderly and those with cirrhosis.

I do think, however, that the biopsy ... is likely to have been under reported in terms of the stage of fibrosis and that the possibility that the biopsy might have represented a higher stage of fibrosis was not appreciated by the clinicians. A fragmented biopsy, such as that in this case, is not one on which to base a prognosis with confidence.

It must be noted that Mr Laing survived 13 years after his diagnosis of carcinoma of the rectum with Duke's C histology, which is an astonishing outcome. I do not feel that even if there had been a better indication of his fibrosis stage in 1996 that it would have been possible to modify the natural history of his hepatitis C virus infection as the treatment available at that time was relatively ineffective and more so in elderly males with cirrhosis. If he had presented now with Pegylated Interferon and Ribavirin available the chances are that he would not have responded to treatment and if I was asked now to consider treatment I would very likely not offer him treatment with Pegylated Interferon and Ribavirin, the best available current therapy, because of his age and cirrhosis and the low probability of a response.[518]

7.280 It is a matter of agreement on the part of Mrs Laing and the other 'patient interest' core participants that there appear to have been no reasonable precautions whereby Mr Laing's death might have been avoided once he had contracted Hepatitis C.[519]


7.281 Factors contributing to the death of Mr Laing were:

(i) Mr Laing died from Hepatitis C-related liver disease.

7.282 Infection with Hepatitis C:

(ii) Mr Laing was infected with Hepatitis C as a result of transmission of blood at the time of his surgery for Duke's C carcinoma on 7 August 1990.

(iii) The surgery saved his life. It was never suggested that surgery could have been carried out without transfusion.

(iv) The donor's infection was discovered in the course of the UK national look-back programme for transfusion-related Hepatitis C in 1995 and the blood used in Mr Laing's operation was traced to the infected donation in the follow-up stages of that investigation.

(v) The donor's infection probably resulted from the transfusion of an infected donation in the 1970s. In 1990, there was no requirement for a policy of excluding recipients of previous blood donations from themselves donating blood.

(vi) In 1990, anti-Hepatitis C testing was in its infancy and had not been adopted to screen blood donations in the UK.

(vii) If the first-generation ELISA tests that were available at the time in 1990 had been used, the donor's Hepatitis C would not have been discovered.

(viii) Surrogate testing for anti-HBc was not in use but, if it had been, it would not have given rise to an inference of possible Hepatitis C: the infected donation, when retrospectively tested, was negative for anti-HBc.

(ix) Surrogate testing using ALT levels was not in use, but if it had been it would not have given rise to an inference of possible Hepatitis C: the donor had normal levels of ALT on two occasions in 1992, once in 1993 and once in 1994.

7.283 Progression of disease:

(x) Mr Laing's Hepatitis C progressed as would have been predicted by current understanding of the disease in a man of his age.

7.284 Mr Laing's management as a patient:

(xi) Mr Laing's management as a patient was an illustration of exemplary care.

Victor Tamburrini


7.285 Mr Victor Tamburrini was born on 27 April 1957. He died at the Royal Infirmary of Edinburgh on 17 November 2004, aged 47 years. The certified causes of death were liver transplant graft failure and recurrent Hepatitis C.[520]

The recovery of Mr Tamburrini's health records

7.286 Health records for Mr Tamburrini were recovered from the Glasgow Royal Infirmary (GRI), the Greater Glasgow and Clyde Community Alcohol Service and the Royal Infirmary of Edinburgh (RIE). In addition, relevant transfusion related records were obtained from the SNBTS. The Inquiry was unable to recover the full GP records of Mr Tamburrini.

7.287 Mr Tamburrini's GP records were obtained by the Crown Office and Procurator Fiscal Service (COPFS) in January 2007 following a request by Messrs Thompsons, solicitors, on behalf of Mrs Tamburrini, to Strathclyde Police, for sight of the records.[521] Mrs Tamburrini was pressing for a Fatal Accident Inquiry (FAI) in to her husband's death. While Mr Tamburrini's other health records continued to be held by the COPFS, from which they were recovered by the Inquiry, the GP records had been returned to the NHS National Services Scotland Practitioner Services. It is likely that they were returned in 2007.[522] That department destroyed the original GP records on 16 June 2009.[523]

The destruction of Mr Tamburrini's original GP records

7.288 In ordinary course, destruction of medical records conforms to the 'Guidance for the Retention and Destruction of Health Records' issued by the former Scottish Office in 1993. In the case of GP records, the guidance recommends a retention period of three years after a patient's death.[524] If the guidance had been followed, Mr Tamburrini's GP records would have been destroyed on receipt by Practitioner Services or shortly thereafter: the three-year retention period had long expired.

7.289 In January 2009 Crown Counsel instructed that there should be no FAI into Mr Tamburrini's death.[525] However, Scottish Ministers continued to consider referring Mr Tamburrini's death to this Inquiry and that was done on 13 November 2009. Destruction of the GP records therefore occurred while consideration was still being given to the reference of Mr Tamburrini's death to the Inquiry.

7.290 How that came about is unclear. The GP records appear to have been returned to Practitioner Services[526] before the decision to instruct no proceedings in relation to an FAI and there has been no explanation why the COPFS took that step while retaining other medical records. So long as a decision on an FAI remained to be reached, the GP records were potentially required as evidence and the COPFS should have been aware of that possibility. At the time the COPFS was not aware of the Scottish Government Health Directorate document retention policy.[527] However, it is clear that the records remained available in the hands of Practitioner Services after the decision by the COPFS on FAI proceedings.

7.291 The destruction of the records by Practitioner Services remains unexplained. However, at the time of their destruction a summary of the GP records was prepared.[528] In addition, the hospital records include correspondence with Mr Tamburrini's GP. The Inquiry is satisfied that the records produced to it were sufficient to enable the investigation of his death. The lack of the original GP records did not inhibit the investigation.

Initial symptoms and diagnosis of Hepatitis C Virus infection

7.292 How and when Mr Tamburrini acquired infection with Hepatitis C is not known. Mr Tamburrini married for the second time on 8 March 1991. His widow, Mrs Jean Tamburrini, had limited information about his medical history before they met in 1987. She knew that he had been in a car accident and had suffered serious burns in September 1984. In general, however, her evidence related to the period from 1987 onwards. In the circumstances she was unable to provide an insight into possible dates of infection before 1987.

7.293 Mr Tamburrini was diagnosed with Hepatitis C in September 2001.[529] By then he had signs and symptoms strongly suggestive of severe liver damage. That would provide the latest date by reference to which estimates of the duration of infection might be made on the basis of knowledge of the natural history of the disease. There was, however, evidence that, in retrospect, indicated he was developing liver disease at an earlier period.

Early signs and symptoms

7.294 At Christmas 1991, Mr Tamburrini felt unwell and could not stop falling asleep. He was doing heavy work at a fruit market as a porter or deliveryman, however, and the possible significance of his condition only became apparent later.[530]

7.295 In about 1994 or 1995 he worked for his uncle in a factory for around 10 months. The work was hard and physical and he had difficulty in maintaining the energy levels required and had to leave the job. He then began working in licensed premises owned by his brother-in-law, first as a barman and then, from about 1997, as bar manager. He suffered from lethargy and slept a lot but his employer was supportive and accommodated him.[531]

7.296 In 1998, Mr Tamburrini was feeling unwell: he had suddenly begun to put on weight, experienced heartburn and had poor appetite. His ankles and abdomen were swollen and he was increasingly lethargic.[532] In May 1998, he went to see his GP complaining of a painless swelling in his right breast.[533] It was recorded that there had been no trauma or serious illness in his recent medical history. He was referred to the GRI where he was seen at the professorial breast clinic. In the referral form, the GP noted that Mr Tamburrini had mentioned a habit of consuming large quantities of alcohol. The hospital report to the GP following examination on 15 July noted that Mr Tamburrini had a history of alcohol abuse. Atypical gynaecomastia (benign enlargement of breast tissue in males) was diagnosed in the right breast and it was proposed that the affected area should be removed. The left breast did not present with similar swelling.[534] On admission on 10 December 1998, it was found that the lump in the right breast which had been noticed first was not palpable and that a lump had developed in the left breast. On the following day bilateral subcutaneous mastectomy was carried out.[535] Mr Tamburrini was discharged from hospital on 15 December 1998 with a note stating that he was well and was to be followed up in clinic.[536]

7.297 Gynaecomastia can be observed in men with advanced liver disease from any cause. Not infrequently it is also seen, in the absence of cirrhosis, in men who are putting on weight, as Mr Tamburrini was, and in heavy drinkers.

7.298 On 27 January 1999, Mr Tamburrini was admitted to the Lister Department of Surgery, at the GRI, as an emergency patient, complaining of severe epigastric (abdominal) pain. He gave a history of diarrhoea about a week earlier. His pain had gradually increased and on admission he had mildly raised serum amylase (an enzyme produced by the pancreas) but no other indicators of severe disease. An ultrasound scan disclosed some large stones in his gallbladder. There was a diagnosis of '(?)Viral induced acute pancreatitis'. He was discharged well, to be followed up in the clinic.[537] He was reviewed on 24 February 1999, found to be well and discharged without further follow-up.[538]

Towards a diagnosis of liver disease

7.299 In 2000, Mr Tamburrini again began to put on weight around his abdomen, gave up exercise because he could not manage it and, on holiday, was depressed and grumpy. He had swollen ankles and could not wear normal shoes.[539] In 2001, the Department of Oral Medicine at the Glasgow Dental Hospital and his GP each separately referred him to the GRI for examination. The Department of Oral Medicine referred him specifically to the Haematology Department and he was seen at Dr Isobel Walker's clinic. The GP's referral letter reported a history of previous admissions and findings and described the basis of the current referral as 'recently developed moderate/severe oedema of both legs', the abnormal accumulation of fluid, clinically apparent as swelling. It reported that Mr Tamburrini's liver function tests were deranged and provided recent values. The referral letter from the Department of Oral Medicine noted 'peri-orbital oedema [swelling around the eyes] and bilateral ankle swelling' in addition to the oral problems for which he had been examined.[540]

7.300 Dr Lorna McLintock of the Department of Haematology reported to the Dental Hospital on 8 August 2001.[541] She noted that the abnormal blood parameters included elevated mean corpuscular volume (MCV), thrombocytopenia, mild eosinophilia and mild reticulocytosis.[542] She thought that Mr Tamburrini's blood parameters all related to liver disease but wished further tests to be carried out. Dr David Mutimer, a Consultant Hepatologist who provided expert testimony to the Inquiry, said that the features reported by Dr McLintock were all seen in patients with advanced liver disease, which was therefore indicated at that time.[543] MCV is a measure of the size of the red blood cells and a high MCV is found typically in patients with cirrhosis, particularly when due to alcohol.[544] Thrombocytopenia (a decrease in the level of platelets in the blood), eosinophilia (a decrease in another blood component, eosinophii) and reticulocytosis (an increase in immature red blood cells) are also seen in patients with cirrhosis or advanced liver disease.[545]

7.301 Mr Tamburrini was reviewed by Dr McLintock on 5 September 2001.[546] She again found his liver function test results to be elevated. She reported to his GP that Mr Tamburrini 'obviously' had significant liver disease. She sent blood for autoantibody serology and hepatitis serology.

Diagnosis with Hepatitis C

7.302 A Hepatitis C test, using polymerase chain reaction (PCR) technology, proved positive[547] and on 26 September 2001 Mr Tamburrini was told that he had contracted Hepatitis C.[548] Mrs Tamburrini was also tested for the presence of the Hepatitis C virus (HCV): she was not infected.[549] Dr McLintock noted that Mr Tamburrini did not feel that he had a history of any high-risk behaviour associated with the transmission of Hepatitis C.[550] Blood tests performed at that time strongly suggested severe liver damage: the results were consistent with cirrhosis and hepatic decompensation. The MCV score was again very high at 111.[551] Dr Mutimer thought that the blood test results would be consistent with cirrhosis and hepatic decompensation due to the effect of alcohol, to Hepatitis C or to a combination of the two.[552] Mr Tamburrini thereafter attended Dr AJ Stanley's Liver Clinic at the GRI before being referred to the Liver Transplant Unit (LTU) at the RIE in February 2002.[553] Mr and Mrs Tamburrini began to understand that the condition was serious.

Possible cause of HCV infection

7.303 There are two main groups of causes of HCV infection. The first group comprises transmission of infection during health care, by transfusion of infected blood, blood components or blood products, or hospital-acquired transmission, for example by needle-stick injury. The second group comprises causes of infection outwith a healthcare setting. Overwhelmingly the commonest cause of infection in the second group, in Scotland, has been intravenous drug use and sharing HCV-infected materials. More rarely, HCV may have been acquired from contaminated tattooing or body piercing equipment. These possibilities will be explored in light of the fact that Mr Tamburrini already had cirrhosis at the latest in 2001 when he was aged 44.

7.304 Mr Tamburrini's medical records were examined to ascertain whether there was evidence of medical procedures that might have involved blood transfusion and created a risk of transmitting infection. The records were examined specifically in an attempt to identify a date of transmission. The examination was not limited to the period within which he might be thought to have acquired infection.

Possibility of infection during an appendicectomy in December 1968

7.305 Mr Tamburrini had an appendicectomy as a child, in 1968.[554] That was the first occasion on which he might have had a blood transfusion. The appendicectomy was noted elsewhere in his medical records.[555] There was no reference to transfusion or to any event of an exceptional nature at the time of the operation that might have indicated a need for transfusion. The appendicectomy scar, in itself unremarkable, was noted throughout the records without comment.

7.306 Professor Willem van Aken was asked to express an opinion on the likelihood of transfusion at the time of the procedure. Professor van Aken was, until retirement, Director of the Board of the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and had a long and distinguished record in that service. He was well qualified to comment on the use of blood transfusion for surgical procedures at the relevant period. In his view it would have been a rarity for anyone ever to have received a transfusion of blood in the course of an appendicectomy in 1968. It would happen only very seldom and only when there was a complication and major bleeding. Most appendicectomy procedures would not have required the transfusion of blood.[556]

7.307 As a medical scientist, Professor van Aken could not rule out the possibility that there had been a blood transfusion. On the evidence as a whole, however, there is no basis for a finding that Mr Tamburrini did have a blood transfusion in 1968. The records do not disclose any complication or major bleeding. Bare possibility could not support a finding that there was a transfusion in the face of Professor van Aken's evidence.[557]

7.308 On a balance of probabilities, Mr Tamburrini was not transfused at the time of his appendicectomy and that procedure cannot have been the occasion of transmission of infection.

Possibility of infection during treatment for burns in 1984

7.309 On 7 September 1984, Mr Tamburrini was admitted to the burns unit of the GRI having sustained extensive surface area burns as a result of a vehicle fire: the accident Mrs Tamburrini knew about. He was transfused with six units of Plasma Protein Solution (otherwise Stable Plasma Protein Solution, SPPS), an albumin preparation, each recorded as having come from a specific batch of product numbered 1194 released by the SNBTS on 10 August 1983.[558] Transfusion of SPPS was a standard procedure in the circumstances, in this application much safer than plasma or whole blood.[559] Severe burns involve the loss of fluid from the circulation: in the vicinity of the burn, blood vessels become dilated and leak protein-rich fluid, creating a risk of shock. Blood pressure drops and there tends to be an urgent need to restore blood volume and to increase osmotic/oncotic pressure, which is a composite of the protein content in the blood and the resistance provided by tissue. In some patients the albumin level in the blood drops. SPPS specifically restores albumin as part of the process of increasing the volume of circulating blood. Mr Tamburrini recovered, and was discharged on 6 October 1984.[560]

7.310 The transfusion of SPPS was the second event that provided a focus for investigation as a possible source of transmission of HCV infection. In the UK, and in Scotland in particular, SPPS was prepared at the material time in accordance with requirements set out in a monograph contained in the British Pharmacopoeia (BP) issued in 1980.[561] The batch from which the SPPS administered to Mr Tamburrini was drawn was prepared in that way.[562] The critical, penultimate stage in the process was described in the monograph:

The albumin fraction, prepared by a suitable fractionation technique, is dissolved in water .... The solution is sterilised by Filtration, distributed aseptically in sterile containers, and sealed so as to exclude micro-organisms. It is then heated to, and maintained for ten hours at, 59.5° to 60.5° so as to prevent the transmission of hepatitis.[563]

7.311 The records relating to the batch were comprehensive.[564] The product in question was pasteurised at 60°C for 10 hours.[565]

7.312 The production process was described in detail by Dr Bruce Cuthbertson, currently Quality Director of the SNBTS.[566] 'Albumin' is the term used to describe a product that contains in excess of 95% albumin protein. SPPS must contain in excess of 90% albumin protein.[567] There is a 'purity' distinction between the products but there is no difference in terms of risk of transmission of hepatitis viruses. Both products are pasteurised by heating at 59.5°C to 60.5°C for 10 hours.[568]

7.313 Albumin has had an almost unblemished record of safety in clinical use since its introduction in 1940 by the US Army for the battlefield treatment of trauma.[569] Albumin products have only twice been reported to transmit hepatitis: the first time in an experiment carried out on human volunteers in the 1940s when pasteurised and unpasteurised albumin doses were administered (those who received unpasteurised doses were infected with Hepatitis B while those who received the pasteurised product were not);[570] the second time, which again involved transmission of Hepatitis B, in 1973.[571] After full investigation it was shown that, in that instance, the pasteurisation process was defective. Pasteurisation was carried out in a bulk tank, after which the preparation was decanted into containers. The structure of the bulk-pasteurisation tank allowed for pockets of material to remain inadequately mixed with the remaining material and thus to fail to be subject to the complete heating cycle.[572] Professor van Aken gave further details of the 1973 incident.[573] Albumin has never been reported to transmit Hepatitis C.[574]

7.314 The BP stipulation for pasteurisation in the final container addressed the risk illustrated by the 1973 incident.[575] The process requirements ensured that after sealing there was no prospect of there being incomplete pasteurisation or of the product being re-contaminated.[576]

7.315 Professor van Aken was asked to comment on whether the word 'prevent' was apposite in the sentence from the BP: 'It is then heated to, and maintained for 10 hours at 59.5°C to 60.5°C so as to prevent the transmission of Hepatitis'. He had no doubt or uncertainty about the use of the word 'prevent' in this context.[577]

7.316 Dr Cuthbertson explained that pasteurisation was the end stage in the production process.[578] Fractionation of plasma extracted various proteins using a variety of biochemical techniques, principally cold ethanol fractionation. The SPPS produced was sterile-filtered to remove bacteria and was then dispensed into bottles in an aseptic filling suite. The bottles and stoppers had already been sterilised separately at 121°C for 15 minutes and held in sterile conditions until used. Four hundred millilitres of liquid were placed in each bottle, the stopper was inserted and an aluminium overcap was put on top. The caps were then sealed. The bottles were crated, reserving two for quality control. The crated bottles proceeded to pasteurisation in a chamber commissioned and developed by the Protein Fractionation Centre (PFC, the manufacturer of blood products in Scotland). The bottles were sprayed with hot water for pre-wash, to remove any protein that might have been deposited on their exterior surfaces in the course of filling or handling. Thereafter the bottles were rapidly heated to 60°C for 10 hours.[579]

7.317 Professor van Aken commented generally on the process of fractionation and in particular on the distribution of virus particles over the range of products.[580] It had been shown that the distribution was uneven, with some fractions containing more contamination than others.[581] Albumin was produced from a fraction that had been found to contain only a minute quantity of Hepatitis C virus after the fractionation process.[582] The major contributor to viral inactivation, however, was the pasteurisation process which followed fractionation. The position relative to the pasteurisation step was summed up by Brian Erstad and others in an article for the journal Pharmacotherapy:

Both HSA [human serum albumin] and PPF are manufactured with pasteurization procedures that have led to an excellent viral safety record based on 50 years of clinical use .... The pasteurization process is effective in eradicating known viral pathogens when good manufacturing practices are followed.[583]

7.318 Professor van Aken's report stated that published studies had shown that heating of albumin for only 10 minutes at 60°C results in levels of virus inactivation and reduction, recognised as providing a very high margin of safety. He pointed out that the pasteurisation of albumin for 10 hours at 60° C is 60 times longer than is needed to inactivate hepatitis viruses.[584]

7.319 He added in oral evidence:

The WHO [World Health Organization] expert committee on plasma products ... has addressed this issue in a very extensive report in which all these papers here are included, and one of the conclusions is in fact that ten minutes at 60 degrees Celsius results in a virus reduction of more than 16 logs, which means that ... it is about a risk of one in 16 millions that still a virus is not inactivated. So it goes well beyond our imagination that there is still some virus left after that period of time.[585]

7.320 The original batch records for batch 1194, from which the SPPS used to treat Mr Tamburrini came, were examined to ascertain the procedure in the particular case. They showed that the pasteurisation cabinet was checked and found to be operating satisfactorily. The loading of the crates was recorded. The temperature was monitored by a Honeywell probe placed in a representative bottle in each crate of 10 bottles. The run was timed and the temperature maintained throughout was recorded as 60°C. The procedure was recorded in detail and explained in oral testimony by Dr Cuthbertson.[586] He noted that this was before the digital age: the data were recorded on charts. There was an independent check that the probes were in fact reading at 60°C. The procedure confirmed that the bottles were all behaving consistently.[587]

7.321 The completed bottles were placed in cages, security-sealed, labelled with the individual batch number and placed in incubation for two weeks at about 30°C. Albumin is a good medium for bacterial contamination[588] and this procedure allowed any bacterial contamination that might be present to grow and become evident. Dr Cuthbertson had signed off the microbiology test results at the time.[589] It was only after quality control on a sample of pasteurised bottles, which included demonstration that the product had been effectively pasteurised, that the product was released for inspection.[590] The caps were inspected to ensure their integrity and the bottles were inspected under direct light and polarised light to look for the presence of visible contamination. Pasteurisation changes the characteristics of albumin from clear to opalescent. Rejection was a common occurrence. From the specific batch in question, 110 bottles were rejected. Most of these will have been because of the presence of fibres in the bottle. Once all the bottles had been inspected they were released for labelling and packing (or discarded had they failed the inspection).[591]

7.322 Professor van Aken carried out an independent review of the records relating to the particular batch.[592] The procedures followed the guidance to pasteurise in the final individual containers as set out in the BP and in WHO guidelines.[593] His conclusions were:

The batch of SPPS administered to Mr Tamburrini was manufactured using methods which were at the time (and still are) widely recognised as being capable of eliminating any risk of virus transmission.

The records of batch number 1194 indicate that its manufacture, and in particular its pasteurisation, was carried out according to recognised industry and pharmacopoeial standards.

The answer to the query therefore is that the transmission of hepatitis C by SPPS is most unlikely ....[594]

7.323 He was asked why he did not say 'impossible' and added in oral evidence:

Well, 'impossible' is a word which I use only very rarely because I have learned through my career that some events you can judge to be highly unlikely or even further, but you have to be cautious, so I cannot oversee the whole chain of events which was related to this incident because it is a chain of events; it doesn't stop with the manufacturing. It is also what happened during the administration, what happened in the hospital, which I cannot oversee, which I have no reports about, which I have no data about. So that's why I thought it would be more accurate to say "highly unlikely".[595]

7.324 Absolute proposition, positive or negative, has to be avoided generally in scientific analysis.[596]

7.325 Reviewing the medical history, Dr Mutimer agreed with the view that it was extremely unlikely that Hepatitis C was acquired as a consequence of administration of that plasma.[597]

Possibility of infection due to manufacturing deficiencies

7.326 The Medicines Inspectorate found a number of deficiencies in buildings and facilities at the Edinburgh PFC on an inspection in 1981 and also deficiencies in manufacturing practices in a further inspection in 1988.[598] The 1981 Medicines Inspectorate report highlighted: (i) inadequate space in some production and storage areas; (ii) unsatisfactory processing conditions; (iii) poor surface finishes; (iv) unsatisfactory work flow patterns which could lead to product mix-up; and (v) unacceptable staff movements through production areas which could lead to contamination of components and products. The 1988 Medicines Inspectorate report highlighted: (i) staff structure; (ii) a need for review of documentation; (iii) a need to expedite the expansion of premises; and (iv) a need to remedy inadequacy of storage areas.

7.327 Suspicion arose in the minds of some interested parties that the deficiencies identified in the 1981 report might have been connected to possible contamination of the SPPS used in Mr Tamburrini's case, or cast doubt on the identification of the materials used in his treatment. The specific question put by Messrs Thompsons, Solicitors, representing the patients, relatives and Haemophilia Society, was 'whether there is any potential link between the documented unsatisfactory state of affairs at Liberton in the 1980s and the possible infection of Mr Tamburrini with Hepatitis C as a result of the transfusion in September 1984'.[599] Professor van Aken was asked to consider these issues. He produced a supplementary report on them and gave oral evidence.[600]

7.328 Professor van Aken set the scene.[601] The inspections were part of the ongoing process of implementing good manufacturing practices in a range of NHS premises where blood products for intravenous use were being manufactured at the beginning of the 1980s. That process took considerable time, especially in buildings and with facilities that were constructed before the statement of manufacturing practice was written: it is easier to design facilities if one has a statement of manufacturing practice than it is to adapt something that already exists. He said that it was easily forgotten that, at that stage, 'the whole issue about safety and quality was different from now' and the introduction of good manufacturing practice was a major change, not just in the pharmaceutical industry but also in plasma fractionation. It required, on the one hand, that facilities were adapted and that equipment was changed and, on the other hand, that personnel were trained in a completely different way. A cultural as well as practical change had to happen. That could not be done overnight: time was required.[602] It is clear that the reports were part of an evolving scheme of regulatory oversight that involved the prescription of work required to upgrade facilities to meet new standards.

7.329 Professor van Aken's initial view on the question posed by Messrs Thompsons was that, while he could not completely discount the proposition, he thought it highly unlikely that the noted problems with the PFC's production facilities had contributed to Mr Tamburrini's infection.[603] The evidence of Dr Cuthbertson was then disclosed to him,[604] which clarified the factual situation. The question posed had suggested to him that viral inactivation studies and manufacturing had not been carried out in separate environments (that is, in separate rooms) but they had, in fact, been separated: measures had been taken to reduce, minimise or completely avoid risk in this area.[605] The risk of mis-labelling and of mixing heated and unheated products had been considered. Dr Cuthbertson's statement gave him 'a good feeling that there is no question of mix-up between material which was pasteurised and material which was not pasteurised'.[606] The visual inspection step was common to all manufacturing facilities and the differences between pasteurised and non-pasteurised albumin products could be clearly seen.[607] He then referred to the possibility that batches could have been contaminated by the re-use of pH probes, especially if they had been used in 'virus-spiked' samples for experimental purposes. The process requirement of pasteurisation of already-sealed bottles excluded that, as did the fact that the Hepatitis C virus, which had not yet been isolated, could not have been in use at the PFC in 1983 in a way that might have contaminated probes.[608] He concluded that the potential link suggested in Messrs Thompson's question was 'impossible'.[609]

7.330 He confirmed his views in answer to questions by Counsel representing the patients, relatives and the Haemophilia Society.[610] There is no basis for a view that a deficiency in plant or in the manufacturing processes at the PFC caused the issue of a product that may have caused Mr Tamburrini's infection.

7.331 While in this context few scientific propositions can be expressed in terms of mathematical certainty, totally excluding alternative possibilities, it is, scientifically, most unlikely that the SPPS administered to Mr Tamburrini transmitted Hepatitis C. In conventional legal terms it was established, beyond reasonable doubt, that SPPS did not transmit Hepatitis C to Mr Tamburrini.

Possibility of infection in the course of surgery in 1998

7.332 The next possible candidate for transmission of infection that was explored was blood transfused on 14 December 1998 following Mr Tamburrini's surgery on 11 December 1998.[611] The mastectomy carried out was complicated by haemorrhage and he required evacuation of a haematoma and blood transfusion.[612] He was transfused with three units of packed red cells, one each from batches 707090QX, 611185X8 and 631627X1. A fourth unit from batch 707135Q3 was pierced and discarded unused.[613] He was discharged on 15 December.[614]

7.333 Mr Tamburrini was diagnosed with cirrhosis in November 2001 and his liver failed to the extent that he required a transplant in October 2002, only some three years and ten months after the December 1998 operation. Dr Bathgate's view was that, in Mr Tamburrini's case, even four years was 'far too short' a period for liver failure as a result of his acquisition of Hepatitis C infection in 1998 to have developed.[615] Dr Mutimer's opinion was that the chances of acquiring Hepatitis C from a blood transfusion in 1998 were 'extremely low indeed' and he noted that, as mentioned in the GP's referral letter of 2 June 1998,[616] Mr Tamburrini already had abnormal liver function tests.[617] As referred to in paragraph 7.297, the gynaecomastia and other symptoms exhibited by Mr Tamburrini in 1998 were suggestive of existing liver disease.

7.334 There were factors other than the issue of time that also tended to exclude the possibility of infection in 1998. Dr Myrtle Peterkin, clinical consultant to the West of Scotland Blood Transfusion Service, was contacted in September 2001 by Dr McLintock and agreed to follow up Mr Tamburrini's transfusion in 1998 as a possible source of his HCV infection. She investigated the sources of the blood components (packed red cells) transfused, and available to be transfused, to Mr Tamburrini in the course of the surgical procedures undertaken. She traced the process from the request for blood to cover the operation through to the record of transfusion. The respective donors' donating histories were traced and the history of the screening of those donations was reviewed.[618] Finally, the archived samples of the donations were repeat-tested with a PCR test for Hepatitis C.[619] Dr Peterkin reported on the outcome of her investigation in a letter of 17 October 2001 to Dr Isobel Walker.[620]

7.335 In oral evidence, Dr Peterkin explained that this was a specific investigation. In ordinary course, the SNBTS did not trace or record the patients to whom blood and blood products were administered; rather, hospital blood banks recorded such use.[621] She was provided with details of the pack numbers derived from Mr Tamburrini's hospital record sheet and traced the records back from there. The records provided a complete audit trail from the transfusion of identified pack or batch numbers of individual units of red cells, prescribed and infused by named clinicians and countersigned by nursing staff, which were correlated with records of the issue of the materials from the SNBTS.[622] From the records, the identities of the individual donors and the date of the donations were identified.[623] Dr Peterkin described what happened next with reference to one of the units:

It is important in cases like this that we don't just focus on the one donation; that is really critical. The index donation, which is why I highlighted it in bold, so that you can refer back to that - but as it were, to make assurance doubly sure that we are not missing any marker of infectivity, we look at the entire donating record. We actually retrieve archive samples from all the donations given and probe these donations as well for the specific markers that relate to the case in point.

So in this case we are talking about a possible Hepatitis C transmission and this is why we look at all those donations with specific references to the Hepatitis C virus, and ... all of the donations which were checked are Hepatitis C PCR negative, including the one that was given to the patient, and this donor had given two donations prior to November 1998, and so this is the full record of this donor that we have looked at.[624]

7.336 The same procedure was carried out with each of the relevant units. The donations had been screened by anti-HCV screen when they were given. On this occasion the archived samples were also screened by HCV PCR test with negative results. Mr Tamburrini did not acquire Hepatitis C from red cells transfused at the time of surgery in December 1998.

Other possibilities

7.337 Excluding transfusion as a cause of infection does not exclude entirely the possibility of infection having been transmitted in hospital. Dr Mutimer commented:

We tend to forget that just being in hospital and having procedures done to us is associated with a risk of - transmission of infection, and that includes Hepatitis C infection. So although the blood products that he has been given are unlikely to be a cause of Hepatitis C transmission, you can never exclude the possibility that he came into contact with Hepatitis C infection during his medical care, not necessarily those inpatient admissions even; it could have been dental or medical treatment that he had at any time in his early life.[625]

7.338 Dr Mutimer thought that Mr Tamburrini's teenage years might define a period of his life when he was more likely to have come into contact with Hepatitis C.[626] There are some issues relating to that estimate, given that it involved an assumption about experimentation with intravenous drug use, or association with others who used such drugs, for which there was no evidence. However, setting aside the speculation about drug use, Dr Mutimer's epidemiological data support the opinion that Mr Tamburrini may have been infected in his early teens. While that might indicate a period when transmission was more likely, it does not help identify the means of infection. The Inquiry heard no evidence concerning any other possible means of infection.

7.339 The written closing submission submitted on behalf of patient interest core participants in relation to Mr Tamburrini's death states: 'In the circumstances the evidence that was heard by the Inquiry did not demonstrate even on the balance of probabilities how Mr Tamburrini came to be infected with Hepatitis C'.[627] That is an accurate statement.

7.340 While the possibility of hospital-acquired transmission cannot be excluded absolutely, however, the evidence did establish, albeit to varying standards of probability, that none of the NHS procedures identified in Mr Tamburrini's case transmitted his Hepatitis C infection.

Possible date of infection with HCV

7.341 Having regard to the whole evidence covering this period, there is no room for doubt that Mr Tamburrini had well-developed Hepatitis C infection and cirrhosis by the end of 2001.[628]

7.342 In a large statistical population of patients infected with Hepatitis C, the median time lapse between infection and cirrhosis of the liver in patients who do not have aggravating factors is about 30 years. At that stage half of infected patients will have developed cirrhosis and half will have less serious damage to the liver.[629] Men may progress more quickly than women. Consumption of alcohol will accelerate the progression to cirrhosis, as more fully discussed at paragraphs 7.345-7.346 below. In patients who acquired HCV infection under the age of 40, it is very rare for cirrhosis to be seen within 10 years of infection and it is uncommon to see it within 20 years of infection. Dr Mutimer's expertise in this area is extensive and his evidence is accepted as reliable. He had particular experience of patients requiring liver transplant procedures in Birmingham. He said:

[I]f I think of the patients that we transplant in Birmingham who have Hepatitis C, who look a little bit like Mr Tamburrini, then the majority of those will have been infected in their early adult years, late teens, early 20s. There will be a history of significant alcohol consumption, not necessarily alcoholism, and the average age at which they come to transplantation is approaching 55.[630]

7.343 The extent to which Mr Tamburrini consumed alcohol was controversial and it is necessary to consider some of that evidence to ascertain whether it helps to determine at least an approximate period of time during which he was probably infected with Hepatitis C. In Mr Tamburrini's case, cirrhosis was diagnosed positively in November 2001.[631] He was approximately 44 years and seven months of age. At the date of his first liver transplant, in October 2002, he was 45 years of age, 10 years younger than the average age among Dr Mutimer's group of comparable patients infected in their teens or early twenties: Mr Tamburrini's Hepatitis C progressed to serious liver disease at a relatively early age. The duration of his underlying liver disease cannot be determined on the basis of these facts alone but they suggest a rapid progression of disease relative to the average.

7.344 Progression to cirrhosis by the end of 2001, assuming a 30-year progression, would suggest a possible date of infection in about 1971, when Mr Tamburrini was about 14 years. Mr Tamburrini's teenage years appear to define the earlier end of the spectrum of possibilities. The later end of the spectrum depends on whether alcohol was a contributory factor in the progression of his liver disease. If alcohol did accelerate the progression of the disease, he may have been infected in the later 1970s or early 1980s, in his early twenties, assuming a period of progression of 20-25 years, on the basis of the ranges provided by Dr Mutimer.

7.345 The most complete scientific explanation of the role of alcohol in the progression of Hepatitis C was given by Professor Thomas. He said:

[I]t's now an accepted fact ... that alcohol increases the level of replication of Hepatitis C and, as a consequence, the liver damage that you see in someone who has Hepatitis C and is in addition taking significant amounts of alcohol, those two factors are synergistic; in other words, they cause more liver damage than the sum of the damage due to the alcohol and the Hepatitis C ... [B]efore we had ways of treating patients with Hepatitis C, one important thing to say was that you can slow down the progression of your Hepatitis C if you reduce your alcohol intake, and the ideal scenario would be that you would be abstinent from alcohol.[632]

7.346 It was well understood by the later 1990s that significant alcohol consumption was associated with more rapid liver disease progression following Hepatitis C infection and with a higher likelihood of development of cirrhosis in those infected with Hepatitis C virus in young adulthood.[633] That alcohol might have, not merely an additive, but a synergistic effect on the progression of Hepatitis C virus infection was suggested around 2004-05 as a result of studies of factors that altered understanding of the effectiveness of replication of the virus.[634] 'Significant' was not quantified in this context. The official guidance set out in the Scottish Intercollegiate Guidelines Network (SIGN) publication 'Management of hepatitis C - A national clinical guideline' published in 2006 and repeated in the updated version published in 2013, is that: 'Even moderate amounts of alcohol (within government recommended guidelines) have been associated with increased liver fibrosis compared to those who abstain'.[635]

7.347 The issue for the purposes of this discussion is whether Mr Tamburrini's consumption of alcohol assists in determining the period within which he acquired Hepatitis C infection. Detailed analysis of his medical records showed a pattern of persistent alcohol use over a period. The earliest reference to 'alcohol consumption in excess' dates from 1995.[636] From then until March 2002 there are about 10 instances of reports that expressly, or by reasonable implication, indicate that statements were made by Mr Tamburrini that he had been consuming significant quantities of alcohol.

7.348 Dr McLintock's letter of 8 August 2001 (referred to above in paragraph 3.300), following examination at the GRI Haematology Clinic, narrated that Mr Tamburrini had reported his alcohol consumption as at least 20 units of alcohol per week and frequently more, normally of beer and red wine.[637] Dr McLintock reviewed Mr Tamburrini on 5 September 2001. On this occasion he reported mild success in cutting down his alcohol intake.[638] When seen at the Gastroenterology Clinic in November 2001, following Dr McLintock's reference, Mr Tamburrini is recorded as reporting a five-year history of drinking approximately 80 units of alcohol per week, which he claimed to have cut down by that date.[639] He was thought 'clearly' to have decompensated chronic liver disease from a combination of alcohol and Hepatitis C.[640]

7.349 On 17 December 2001, Mr Tamburrini was seen at the GRI Liver Clinic by Dr Stanley. He was said to have been keeping fairly well and to have reduced alcohol consumption to a glass of wine every week or two.[641]

7.350 In January and February 2002, Mr Tamburrini attended the GRI Gastroenterology Unit for tests and was referred to the Liver Transplant Unit (LTU) at the RIE for assessment for transplantation.[642] He reported that he had been off alcohol for three months.[643] After attendance at the LTU on 25 February 2002, the discharge report dated 5 March sent to Mr Tamburrini's GP and copied to Dr Stanley commented on a number of matters including the consumption of alcohol.[644]

7.351 The letter of 5 March 2002 provided a careful and detailed professional review of Mr Tamburrini's history to the end of February 2002. It indicated that his period of abstinence was shorter than reported at the end of 2001 and followed a long period of sustained drinking: 100 units a week of wine and beer over the previous eight years. He had managed to remain abstinent for about six weeks in November and December 2001 but had relapsed at Christmas time and at that stage he was drinking five to six units per week.[645] On his referral from Liaison Psychiatry, at the RIE, to Psychiatry at Parkhead Hospital, Glasgow it was noted that, on review of the GRI notes, Mr Tamburrini had been told to abstain from alcohol on at least two occasions. He was asked by the transplant team to abstain completely.[646]

7.352 At that time, Mr Tamburrini was referred to the Community Alcohol Service of Greater Glasgow Primary Care NHS Trust where he was seen by a Community Psychiatric Charge Nurse, Audrey Ewing (later Audrey Russell, after her marriage). There, he gave an account of seven years of heavy drinking which had escalated to 50-100 units of alcohol per week over five days when he had worked in the public house trade. Before that he drank very little. He said that, when very young, he had experimented with drugs, later identified as amphetamines and cannabis.[647] He did not keep follow-up appointments at the Community Alcohol Service, cancelling many.[648] By August, however, he had completed all relapse-prevention sessions and his support from the Service was terminated.[649]

7.353 While the reports show wide variation in the volume of alcohol reportedly consumed, the overall picture presented was of significant and sustained consumption. As reported by Dr Seonaid McCallum of the Department of Psychological Medicine, at the RIE, to Dr Jauhar, Consultant Psychiatrist, at the Parkhead Hospital, on 6 March 2002, psychiatric examination disclosed that:

Initially Mr Tamburrini denied that he had an alcohol problem but during ... interview he admitted that indeed, although he had managed to stop drinking, sustained abstinence was a problem for him. He also had limited insight into the effect excess alcohol can have in conjunction with hepatitis C and was unaware that it can cause accelerated liver failure. I felt that at the end of the interview he was beginning to show some motivation and insight into his alcohol problem. He did not give a history of alcohol dependency, rather his problem was one of harmful alcohol use.[650]

7.354 As reported by Dr McCallum, Mr Tamburrini had given a history of drinking 50-100 units of alcohol per week. He had achieved a six-week period of abstinence before Christmas which he had been unable to maintain. Dr Mutimer considered that psychiatric assessment as perhaps the most expert undertaken during Mr Tamburrini's psychological assessment for liver transplantation.[651] His evidence is accepted. It is to be noted that Dr McCallum's view was that Mr Tamburrini's problem was of harmful alcohol use, particularly in the context of his HCV infection, of which he was unaware until 2001. It is nowhere suggested that he was 'an alcoholic' or otherwise dependent on alcohol.

7.355 Dr Mutimer said of Mr Tamburrini:

In my opinion, both hepatitis C virus infection and alcohol caused cirrhosis and subsequent hepatic decompensation. It is not possible to determine the relative contributions of hepatitis virus infection and alcohol to his liver damage. The duration of his hepatitis C infection is unknown. It is possible that he was infected with hepatitis C at a young age ....It is also possible that he was infected at a much later date .... At times in his life, his alcohol intake was excessive and certainly sufficient to cause liver damage. His reported (or at least documented) alcohol consumption varies quite significantly. Perhaps the most expert assessment would have been undertaken during his psychological assessment for liver transplantation. That assessment stated that he consumed 50 to 100 units of alcohol per week for eight years.[652]

He underwent liver biopsy in August 2002. The liver biopsy showed that he had a micronodular cirrhosis and that the changes were consistent with chronic hepatitis virus infection. At that time, there were no particular signs of alcoholic liver damage. This observation is not surprising and does not exclude alcohol as a significant cause of his liver damage. It seems likely that he was abstinent from alcohol during all of 2002 and that his alcohol consumption during the last quarter of 2001 was not excessive. I believe that the histological changes associated with alcoholic liver damage could have resolved during his period of abstinence. Indeed the hepatologists in Edinburgh would have been encouraged by the histological appearances which would have reassured them that there was no significant recent alcohol intake. In summary, I believe that hepatitis C and alcohol contributed to his liver disease.[653]

7.356 Dr Bathgate and Dr Mutimer both commented on consumption of alcohol as a possible factor which might have contributed to Mr Tamburrini's underlying liver disease. Dr Bathgate described experience in south east Scotland which indicated that alcohol was the major co-factor seen in cases such as Mr Tamburrini's.[654] Dr Mutimer was more positive: Mr Tamburrini's underlying liver disease was secondary to HCV infection and alcohol. He was, however, unable to determine their relative contributions.[655]

7.357 The reports of alcohol consumption were not challenged as inaccurate records of what Mr Tamburrini told medical staff. It was submitted that the basis on which the amounts were 'estimated' was not known but the written records indicate that they reflect what Mr Tamburrini told the physicians and other relevant health care professionals, including Nurse Audrey Ewing. The reports were clearly not believed by the family's wider circle, however. Mrs Tamburrini and friends of the family submitted affidavits in which they stated variously that Mr Tamburrini did not drink heavily.[656] Mrs Tamburrini has stated that in the late 1980s her husband did not drink during the week, except perhaps for celebrations, and did not drink excessively. When he began working in licensed premises, he would have a couple of beers with his friends but they did not have money to drink heavily. She did not recall any increase in his drinking when he began bar work. They had both abstained in 1996 for a period. She comments that the family are incredulous that it should be recorded in the medical records that he drank 50-100 units of alcohol a week.[657] Mr Charlie Cunningham never saw Mr Tamburrini drink to excess. He would have a couple of drinks in a night club. He did not recall any escalation in his drinking when he started working in the bar.[658] Mr Stephen Clocherty said that, at the fruit market, because of the early start, Mr Tamburrini would not have been able to stay out late drinking. He did not see any change when Mr Tamburrini went to work in the bar. He thought that it was 'pure nonsense' to say that he drank 50-100 units of alcohol a week.[659] Mr Fisher, the owner of the establishment where Mr Tamburrini worked, said that no one drank at work. During the week they would have a bottle of beer while tidying up. At weekends they would sometimes have two or three drinks before going home. He remembered Mr Tamburrini being advised to stop drinking before his first transplant. He never saw him drink anywhere near 50-100 units of alcohol a week.[660]

7.358 There are three significant problems with this evidence. In the first place, some of it does not relate to the period over which Mr Tamburrini is likely to have been developing liver disease. Mrs Tamburrini met her husband in 1987.[661] Mr Fisher knew him as brother-in-law of Mrs Tamburrini and speaks of no earlier acquaintanceship.[662] Mr Cunningham and Mr Clocherty knew Mr Tamburrini from school and from work but speak of very general impressions only. Secondly, in the nature of things, the witnesses could never give more than impressions from observation of Mr Tamburrini's drinking when they were present. Thirdly, standing the records, the evidence contradicts what Mr Tamburrini himself told medical staff. Balancing these statements against contemporaneous records of Mr Tamburrini's own statements, the witnesses' affidavits cannot be accepted as reliable evidence of Mr Tamburrini's consumption of alcohol over the period when he was developing significant liver disease, which probably began long before 1987.

7.359 Further, the evidence is misdirected so far as the issues before this Inquiry are concerned. It has not been suggested that Mr Tamburrini was generally adversely affected by alcohol, or drank to excess in any conventional sense that implies drunkenness. As noted above, Dr McCallum's view was that Mr Tamburrini's problem was of harmful alcohol use, particularly in the context of his Hepatitis C virus infection. In the progression of HCV-related liver disease, even moderate alcohol consumption may play a part in accelerating damage. On his own reports there were clearly long periods when Mr Tamburrini drank alcohol regularly.[663] He frequently reported consumption, inconsistently as to amount, at periods when his developing symptoms could have been related, in whole or in part, to his alcohol habit. The conditions reported in Mr Tamburrini's medical records and described above frequently have plausible associations with alcohol.

7.360 It is not possible to quantify precisely the effect of alcohol in the progression of Mr Tamburrini's liver disease. However, accurate estimates of quantity are unnecessary in light of the expert evidence led. On the evidence of the medical records, there was a pattern of alcohol consumption over a period of years that was highly likely to have accelerated the progression of liver disease due to his infection with Hepatitis C. It made it more likely that he would become one of the minority of those infected at a young age (under 30 years) who develop cirrhosis sooner rather than later.

7.361 Given a relatively short period of progression from infection to cirrhosis, the history narrated above nevertheless indicates that alcohol was a contributory factor. That was the view of the medical witnesses, which is accepted.

7.362 As set out in paragraphs 7.299-7.300 above, Mr Tamburrini's abnormal blood parameters found in 2001 were thought by his clinicians at the time to be indicative of liver disease. Dr McLintock thought that their most likely cause was liver disease probably caused by alcohol. Mr Tamburrini had reported his consumption to her as 20 units per week.[664] Dr Mutimer commented that, in Mr Tamburrini's case, the gynaecomastia reported earlier in 1998 would be consistent with alcoholic liver damage, with HCV infection, and also with damage due to both alcohol and HCV infection. His MCV recorded at that time was in keeping with alcohol excess.[665] Some medications used to treat patients with advanced liver disease can also cause gynaecomastia but there is no record of Mr Tamburrini taking such medications at the time.[666] The medical evidence was consistent: by the end of 2001 there was established liver disease, consistent with the consumption of alcohol and Hepatitis C.

7.363 In January 1999, when suffering from acute pancreatitis, Mr Tamburrini was advised to abstain from alcohol. Choledocholithiasis (the presence of stones in the bile duct) and excess alcohol consumption are both important causes of acute pancreatitis. Either might have precipitated the episode of pancreatitis he had at this time.[667] From the contemporaneous medical records, his pancreatitis was clearly thought to be related to some extent to his drinking, although it was formally recorded that it might have been due to preceding viral infection.

7.364 As discussed at paragraph 7.355, it is accepted that Mr Tamburrini was abstinent from alcohol from late 2001 until his death in November 2004. Alcohol did not contribute to the failure of either the first or second liver transplant grafts received by Mr Tamburrini or cause, or contribute to the cause of, his death. It is accepted that the cause of death was unrelated to alcohol consumption. The progression of his liver disease following transplantation was independent of those factors.

7.365 In summary, consumption of alcohol was a contributory factor in the progression of Mr Tamburrini's liver disease to cirrhosis at a relatively young age.

Later progression of disease

7.366 On 12 November 2001, an abdominal ultrasound scan was carried out at the GRI liver clinic.[668] There were changes consistent with liver cirrhosis and it was decided to proceed to Magnetic Resonance Imaging (MRI) scan.[669] The MRI scan on 20 November 2001 showed underlying cirrhotic change in the liver, with liver cirrhosis, especially in the right lobe. There was no underlying focal mass and no evidence of hepatoma (liver cancer)[670] and there was no overt portal hypertension (high blood pressure around the liver).[671] However, albumin levels indicated advanced liver impairment and raised alphafetoprotein (AFP) levels suggested the possibility of hepatoma despite the negative scans.[672] Dr Stanley reported to Mr Tamburrini's GP on 13 December that there were a few spider naevi (visible red lines on the skin indicative of cirrhosis of the liver) on examination but no definite ascites (fluid in the abdomen, a marker of liver function).[673]

7.367 On 28 November 2001, Mr Tamburrini was reviewed at the GRI Haematology Clinic by Dr Maclean. It was noted that significant macrocytosis (abnormally large red blood cells indicative of anaemia) persisted.[674] On 17 December, he was seen at the Liver Clinic by Dr Stanley. He was said to have been keeping fairly well. Rising AFP levels were still of concern and thought to indicate the need for a liver biopsy.[675] On 8 January 2002, Dr Stanley noted an AFP level of 366 and thought the rising pattern suggested hepatoma.[676] Dr Mutimer explained that the magnitude of the AFP level was informative. If it was in the thousands, that almost always meant that there was liver cancer. When it was in the hundreds, as it was in Mr Tamburrini's case, then it could simply be associated with an inflamed liver rather than with cancer but tests would be performed to exclude the possibility of liver cancer.[677] Investigations proceeded on 7 February 2002. A contrast enhanced three phase scan and an ultrasound scan confirmed underlying liver cirrhosis but there was no underlying hepatic mass. Gastro-oesophageal varices and varices along the lesser curve of the stomach were identified. The impression was of underlying liver cirrhosis, with overt portal hypertension (pressure within the portal vein from the liver is increased and may lead to bleeding) but no hepatoma.[678] Dr Stanley wrote to Mr Tamburrini's GP on 15 February with these results.[679]

7.368 On 14 February 2002, Dr Stanley referred Mr Tamburrini to Dr Simpson, consultant hepatologist at the RIE LTU for assessment.[680] At that time, there remained some concern that Mr Tamburrini had developed primary liver cancer.[681] Dr Stanley was concerned about a rising level of AFP in his blood test, an indication of possible hepatocellular cancer. That was a legitimate concern at the time but events were to show that Mr Tamburrini did not have hepatocellular cancer. Dr Stanley reported that two ultrasound scans, an MRI scan and a contrast CT scan[682] had been carried out which disclosed liver cirrhosis, varices, and stones in the gall bladder but no splenomegaly (enlargement of the spleen). No scan had shown evidence of underlying hepatocellular cancer but ascites and poor synthetic liver function were noted.[683]

7.369 Mr Tamburrini was admitted to the RIE LTU on 25 February 2002.[684] Dr MacGilchrist's registrar reported to Mr Tamburrini's GP, copied to Dr Stanley, following discharge on 2 March 2002. The discharge letter, dated 5 March, commented on past medical history, as understood at the time, clinical findings, test results and consumption of alcohol.[685] Comprehensive tests were carried out. Mr Tamburrini was cytomegalovirus (CMV) and Hepatitis C positive.[686] Dr Bathgate thought that the results showed moderate impairment of liver function at this stage.[687] Cirrhosis was confirmed during the assessment for liver transplant. Because Mr Tamburrini reported that he was still drinking alcohol he was thought not to be a suitable candidate for transplant: prior to becoming eligible for listing for liver transplant, a period of abstinence (usually six months) is required. In the meantime, other tests were carried out to follow up the risk of hepatoma.[688] It seems clear that Mr Tamburrini remained abstinent from alcohol from this time, as instructed.

7.370 He was reviewed at the RIE LTU on 4 April 2002.[689] His AFP level had fallen. A CT scan using Lipiodol, a contrast medium, was carried out shortly before his clinic appointment and the results were 'against him having hepatocellular carcinoma'.[690] A triple-phase CT scan carried out on 21 June did not indicate any focal abnormality of his liver.[691] He was to be reviewed in six weeks.[692] Mrs Tamburrini recollected that monthly reviews were arranged.[693] In July, his AFP had risen again and Dr Stanley asked the LTU to ensure early reassessment.[694]

7.371 He was seen at the LTU on 4 July 2002. His AFP level was seriously raised, as were other levels. The recent CT scan results were thought to indicate that the AFP level indicated ongoing Hepatitis C activity rather than the presence of a tumour. Further review in two months was arranged.[695] Dr Bathgate thought that the AFP level noted on 4 July was quite concerning.[696]

7.372 Mr Tamburrini was re-admitted to the LTU on 13 August 2002 for formal liver transplant assessment. After extensive review, including liver biopsy, Dr MacGilchrist's registrar reported at length to Mr Tamburrini's GP. There was cirrhosis with mild ongoing inflammation thought to be due to Hepatitis C. He was CMV and HCV positive. The conclusion at that stage was that there was increasing active viral replication but no indications of hepatocellular carcinoma and transplantation was to be delayed as long as possible in view of the fact that he was asymptomatic of liver disease.[697]

The decision to proceed with a liver transplant

7.373 Mr Tamburrini next attended the LTU on 10 October 2002. By this stage, Dr Simpson noted that he was becoming more symptomatic. He was increasingly tired and having to sleep during the day. He was not sleeping at night. He was getting night cramps. The reversal of his sleep pattern was an indication of early encephalopathy (brain dysfunction).[698] His weight was increasing and he felt swelling in his ankles and abdomen. His AFP level had fallen further. Following examination it was decided to admit him on 17 October and list him for liver transplantation.[699]

7.374 He was admitted on 17 October but found to be very unwell. Mrs Tamburrini explained that her husband's health had started to deteriorate rapidly by this point.[700] He had become confused and jaundiced. He complained of fever and abdominal pain over three days. On examination he was septic and had evidence of spontaneous bacterial peritonitis. He was treated intensively. At this stage, Mr Tamburrini signed a contract of alcohol abstinence and was officially put on the transplant waiting list and allowed home on 25 October.[701]

7.375 However, on that day a suitable donor liver was found and he was re-admitted. He had a liver transplant on 26 October 2002. He required intensive care and treatment after the operation. There were complications of bacterial peritonitis and renal impairment (which resolved without the need for dialysis). He progressed to a good recovery and was allowed home on 15 November 2002.[702] No hepatocellular cancer was found in the explanted liver.[703]

Post-transplant observation

7.376 On 19 November 2002, Mr Tamburrini attended a planned post-operation review at the LTU. He complained of abdominal pain. Clinically, he appeared unwell and in obvious pain and was admitted for investigation.[704] There was free fluid within the abdomen. After extensive tests, it was found by ERCP procedure (endoscopic examination)[705] that there was a leak from his bile duct at the anastomosis, the biliary connection with the implanted liver. The ERCP was complicated by pancreatitis but the stricture was dilated and a stent was inserted to try to stop the leak. It was anticipated that he would require to be re-admitted for assessment of the need for further surgery of the anastomosis.[706] He was discharged home on 13 December. Dr Mutimer thought that inflammation from the recurrence of Hepatitis C and poor drainage via the bile duct as a result of the stricture were both relevant to subsequent damage of the implanted liver.[707]

7.377 Mr Tamburrini attended Dr MacGilchrist's clinic on 17 December 2002. A report was sent to his GP.[708] On discharge, Mr Tamburrini remained generally well, with no abdominal pain and reduced drainage of fluid. The prospect of further surgery to renew the connection was kept open. He was reviewed on 14 January 2003 and an ultrasound examination showed a normal liver with no evidence of collection around his biliary tree.[709] He reported at a clinic appointment on 28 January feeling well and said that he was thinking of going back to work.[710]

7.378 Mrs Tamburrini reported that, after discharge, her husband lost the previous excess fluid and recovered his normal condition. He received medication to prevent rejection of the implanted liver.[711]

7.379 After a clinic visit on 27 February, Mr Tamburrini was admitted to the LTU for further examination on 10 March 2003. Tests confirmed that there was no obvious debris or stones. There was a suggestion of focal hepatic artery stenosis (narrowing), possibly at the anastomosis, with very turbulent flow. An ERCP procedure was carried out on 11 March. Ultrasound examination and ERCP showed that the bile duct was dilated above an anastomotic stricture. This required placement of a new endoscopic stent. Mr Tamburrini's bilirubin level fell slowly, which suggested that the endoscopic stent was providing biliary drainage.[712] Treatment of his possible hepatic artery stenosis was deferred.[713]

7.380 Mr Tamburrini was reviewed in April and June 2003. It was decided to continue monitoring his condition.[714] On 24 July 2003, he was reviewed at the LTU when he reported feeling much better. At that stage, it was thought that his biliary stent should be removed in September.[715] It was arranged that he would be admitted for his annual biopsy following a holiday in October.[716] Mrs Tamburrini reported that, on 27 August 2003, at a family event, he was bloated and jaundiced.[717] The ERCP was repeated in September 2003. This showed that the anastomotic stricture persisted. The stent which had been placed six months earlier was not visible. In September it was decided that no further intervention should take place.[718]

7.381 The couple went on holiday but Mr Tamburrini's sleeping pattern was disturbed and he again became jaundiced. His ankles and abdomen were swollen.[719] He was seen at the LTU on 6 November 2003. His symptoms of 'obstructive' jaundice were noted. Further tests were arranged with specific reference to the state of his hepatic artery.[720]

7.382 Additional investigations were performed at about that time. These were highly technical. There were differing opinions about what was shown and in particular whether there was restriction of blood flow. The appearance of the biliary tree was similar to that shown on previous ERCP scans. There was a new finding of multiple upper abdominal fluid collections of uncertain nature. Liver biopsy showed established cirrhosis with evidence of recurrent and active Hepatitis C infection. It was decided to repeat ERCP and stenting across the anastomotic stricture. Antiviral treatment was also considered.[721] It was noted at that stage that his Hepatitis C was Genotype 1.[722] Dr Bathgate explained that Genotypes 1, 2 and 3 are commonly found in Scotland. Antiviral therapy for Genotype 1 usually requires 12 months with a success rate of less than 50%, whereas treatment for Genotypes 2 and 3 requires six months with an 80% success rate. Treatment is less effective in individuals with cirrhosis and after liver transplant.[723] Mr Tamburrini's prospects were relatively poor.

7.383 On 4 December 2003, Mr Tamburrini was seen by Dr Bathgate and treatment of his Hepatitis C was discussed.[724] Poor liver function persisted. Dr Bathgate thought that Mr Tamburrini was unlikely to tolerate any treatment in his then existing state.[725] Options would be discussed in January. Dr Bathgate thought that treatment of the Hepatitis C would have to have been 'fairly aggressive', given his history.[726] In January 2004, his condition deteriorated seriously and he was confused, disorientated and jaundiced.[727] He was admitted on 13 January to the RIE. Again tests showed evidence of cirrhosis likely to be secondary to Hepatitis C. Hepatitis C had returned and he needed a second transplant.[728]

Second liver transplant

7.384 A donor liver became available on 4 February and he had a second liver transplant operation.[729] The surgeon found a dilated and thickened donor bile duct. There was also portal vein thrombosis. Dr Mutimer considered that the appearance of the donor bile duct suggested that biliary complications (in addition to the recurrent Hepatitis C infection) had probably contributed to the development of cirrhosis and graft failure.[730] He expanded on his views in oral evidence. He thought that, during the first year post-transplant, the team were clearly having problems with the bile duct. It was his impression that they thought they had largely resolved that problem but that the finding of the dilated, thickened bile duct at the time of re-transplantation suggested that perhaps that was a problem which had not, in fact, been completely resolved.[731]

7.385 Mr Tamburrini developed post-operative biliary peritonitis secondary to a leaking enterostomy. Further treatment and surgery was required. He made an eventual recovery from that admission[732] and was discharged on 28 February, with a recall date in March to consider antiviral treatment for Hepatitis C.[733] Mr Tamburrini was examined on 16 March 2004 and it was found that his liver function tests had deteriorated.[734] The clinicians were concerned that he was susceptible to aggressive Hepatitis C recurrence.[735] He was to be reviewed by Dr Bathgate, with in-patient ultrasound and liver biopsy examinations.[736] Thereafter, antiviral therapy with a combination of Interferon and Ribavirin was commenced during in-patient care between 23 and 29 March and he had a further liver biopsy. A report was sent to his GP: he was to return for review on 8 April. At this stage, Mr Tamburrini was seen by the specialist Hepatitis C nurse and told what to expect from the treatment.[737]

7.386 Mr Tamburrini continued to attend hospital. On 22 April 2004, he was reported to be tired, lacking in energy and looking unwell although he did not complain of being depressed. In contrast, Mrs Tamburrini had noted that he was grumpy at this time.[738] Mr Tamburrini showed considerable fortitude throughout this period. The antiviral treatment caused diarrhoea. Balancing treatment against his tolerance was necessary.[739] His HCV level was measured on a number of occasions during antiviral therapy. Despite the therapy, his HCV level remained extremely high and there was no obvious improvement from the therapy.[740]

A grave prognosis

7.387 Mr Tamburrini was an in-patient at the RIE from 1 to 15 June 2004. Among the tests carried out, liver biopsy showed fibrosing cholestatic hepatitis (an aggressive type of Hepatitis C generally seen in patients who are immunosuppressed)[741] caused by recurrent Hepatitis C.[742] The prognosis was very grave and there were few options for treatment.[743] Antiviral therapy was increased and other elements of his therapy were re-balanced. He required the additional use of erythropoietin and other haematologic growth factors.[744] He was reviewed again, on 15 July and 6 September.[745] On 14 September liver ultrasound had been unable to detect flow in the portal vein. There was a cystic collection in the left lobe of the liver as well as splenomegaly and moderate ascites. A further liver biopsy was carried out. His treatment now involved the optimum dose of pegylated Interferon and Ribavirin, which he managed to tolerate well, but he required blood transfusions every two to three weeks to counter side-effects of the Ribavirin treatment.[746]

7.388 Despite treatment, his condition deteriorated. On 7 October 2004, he was again admitted to the RIE. He was suffering from severe lethargy and fatigue, weight loss and significant depression. He had a fever and was treated with antibiotics. He developed increasing hepatic decompensation, with increasing ascites and episodes of recurrent encephalopathy. He required paracentesis, the drawing off of fluid. A third transplant could not be considered. The antiviral treatment was stopped. His care regime was changed from aggressive therapy to palliative care after discussion with Mrs Tamburrini. He died on 17 November 2004.[747]

Mr Tamburrini's treatment and management

7.389 Asked to comment on whether Mr Tamburrini's treatment and management were appropriate Dr Mutimer said in his report:

[Mr Tamburrini] clearly had significant liver damage prior to the diagnosis of Hepatitis C virus infection in October 2001. His medical attendants assumed that the abnormal liver function tests were due to the consumption of alcohol. The hospital admission with possible pancreatitis was also in favour of an alcoholic aetiology for the abnormal liver function tests. In general, alcohol-induced pancreatitis is only seen in patients with quite high levels of alcohol consumption. I cannot determine from the medical files if attempts were made to engage the patient with services that might modify his alcohol consumption. That would have been appropriate. Eventually, he developed overt liver failure. It was appropriate that he was screened for viral hepatitis. That confirmed hepatitis C infection. His subsequent management seemed entirely appropriate. He was advised to abstain from alcohol and largely achieved that. He underwent appropriate psychological assessment. He was placed on the liver transplant waiting list and underwent liver transplantation. All of that seemed quite appropriate. He had significant complications after transplantation. Those complications principally involved damage to the bile duct. This is a recognised complication after liver transplantation and attempts to investigate and manage the biliary problems seem entirely appropriate. It is possible, however, that inadequate drainage of the bile duct contributed to liver damage and the development of cirrhosis. It was quite reasonable to attribute the rapid development of cirrhosis (in the transplanted liver) to the hepatitis C infection. Certainly it would have made a significant contribution. It is recognized that re-transplantation for aggressive Hepatitis C infection can be associated with aggressive recurrence in the second transplanted liver. Therefore, it was quite reasonable and appropriate to plan for early antiviral therapy after re-transplantation. It was appropriate that antiviral therapy was deferred pending resolution of the early post-operative complications. Indeed, antiviral therapy was commenced six weeks after re-transplantation at a time when liver graft function was good and biopsy confirmed that little damage had been experienced.[748]

7.390 In Dr Mutimer's opinion, antiviral therapy appeared to have been fully clinically justified: the physicians were concerned that aggressive Hepatitis C recurrence would lead to early graft damage and graft failure. The use of erythropoietin and growth factors enabled the continued administration of antiviral therapy despite suppression of the bone marrow. Suppression of the bone marrow including the leucocytes may have contributed to infection. As the patient died, there was a complicated picture of marrow suppression, possible infection and serious liver damage. Dr Mutimer stressed that, while the drugs administered were 'very toxic', in his opinion there was nothing wrong in the decision to administer the drugs or in the way they were administered, under the circumstances.[749]

7.391 Dr Mutimer concluded his assessment of the appropriateness of Mr Tamburrini's treatment and management:

Despite antiviral therapy, it appears that there was very aggressive hepatitis C recurrence with development of significant liver damage by June 2004. Under that circumstance, it was quite reasonable to persist with antiviral therapy. Unfortunately, antiviral therapy can have quite significant haematologic side effects. The patient would have been susceptible to infection. Susceptibility to infection would have been a consequence of liver dysfunction and bone marrow suppression. In summary, I believe that this man's treatment and management were appropriate.[750]

7.392 That assessment of the position is accepted.

Cause of death

7.393 The cause of death as given in the death certificate was liver transplant graft failure and recurrent Hepatitis C.[751] Dr Bathgate agreed with the causes given.[752] In his opinion, the transplant graft failure was caused by Mr Tamburrini's Hepatitis C infection. Severity was a function of several factors, including the concentration of the virus and the age at which the patient's own liver had deteriorated. The younger a person was when infected, the worse the likely outcome following liver transplantation. It was likely that Mr Tamburrini was in that category. In Dr Bathgate's view, Mr Tamburrini was at 'the worst end of the spectrum' of Hepatitis C infection.[753]

7.394 Dr Mutimer thought that the final cause of death was difficult to ascertain but that contributing factors were aggressive Hepatitis C recurrence and antiviral therapy. Available antiviral treatment was a challenge when given to patients who were as sick as Mr Tamburrini and who were receiving so many other medications. It was recognised that the toxicity of antiviral treatment was much greater in that setting than in giving the drugs to the average non-transplant patient with Hepatitis C. He thought that Mr Tamburrini did have significant side-effects from the antiviral drugs. Dr Mutimer used these drugs in treating his own post-transplant patients and they suffered many of the same problems. In his view, Mr Tamburrini died as a consequence of HCV infection and the antiviral therapy that was required in his case. Dr Mutimer's evidence that antiviral therapy, though appropriate, was a contributory factor to mortality is accepted.[754]


7.395 Factors contributing to the death of Mr Tamburrini were:

(i) A clinically severe form of Hepatitis C.

(ii) Acceleration of cirrhosis after the first transplant associated with problems at the site of the biliary anastomosis which probably led to hepatic artery impairment, local leak of bile and infection, and the portal vein thrombosis found at the operation for his second liver transplant.

(iii) Profuse HCV replication after the second transplant probably associated with further biliary and vascular problems, which led to accelerating cirrhosis and fibrosing cholestatic hepatitis.

(iv) Liver transplant graft failure.

(v) The antiviral treatment given to prevent damage to the second graft.

7.396 Infection with Hepatitis C:

(vi) On the evidence available, with the exception of the possibility of hospital acquired infection, it was established to varying standards of probability that the known NHS procedures in Mr Tamburrini's case did not transmit Hepatitis C infection:

a. On a balance of probabilities, having regard to the whole evidence available, Mr Tamburrini was not transfused at the time of his appendicectomy operation in 1968.

b. It was proved beyond reasonable doubt that SPPS did not transmit Hepatitis C to Mr Tamburrini in 1984.

c. It was established beyond reasonable doubt that Mr Tamburrini did not acquire Hepatitis C from red cells transfused at the time of surgery in December 1998.

(vii) No connection was demonstrated between any deficiency in plant or process at the PFC and the infection of Mr Tamburrini with Hepatitis C.

(viii) On epidemiological grounds, it is likely that Mr Tamburrini acquired HCV infection in his late teens or early 20s.

(ix) The cause of that infection is unknown.

7.397 Progression of disease:

(x) Mr Tamburrini had probably developed advanced liver disease by July 1998.

(xi) His gynaecomastia was likely to have been a symptom of that disease.

(xii) Consumption of alcohol was a contributory factor in the progression of Mr Tamburrini's liver disease to cirrhosis, and the need for the first transplant in October 2002.

7.398 Mr Tamburrini's management as a patient:

(xiii) Mr Tamburrini's care and management as a patient were appropriate.

7.399 Alcohol as a cause of death:

(xiv) Consumption of alcohol did not contribute to the failure of either the first or second liver transplant grafts received by Mr Tamburrini, or cause, or contribute to the cause of, his death. It is accepted that the cause of death was unrelated to alcohol consumption.

1 The SNBTS is one of the health support services provided by the Common Services Agency (CSA) for the Scottish Health Service. The CSA is the designated Core Participant on behalf of the SNBTS.

2 Death Certificate [BLA.001.2118]

3 Family history in Glasgow Royal Infirmary (GRI) records [BLA.001.2121] to [BLA.001.2123] and [BLA.001.2126]

4 Dr Colvin - Day 2, page 76; GRI pro forma for assessment of haemophilia etc [BLA.001.2164]

5 A different blood coagulation disorder. See the Preliminary Report at paragraphs 3.15-3.17

6 Letter from GRI to GP dated 3 June 1971 [BLA.001.2149]

7 Dr Colvin's report [BLA.001.2281] at 2284; Letter from GRI to GP dated 9 April 1971 [BLA.001.2151]

8 Factor VIII level is a measure of coagulant activity. See Chapter 2, Patients at Risk, paragraph 2.26 for discussion of relative levels of severity.

9 Dr Colvin - Day 2, pages 79-84; Dr Colvin's report [BLA.001.2281] at 2283

10 GRI pro forma for assessment of haemophilia etc [BLA.001.2164]; RIE clinical note dated 20 March 1996 [BLA.001.1740]; Dr Colvin - Day 2, page 78

11 GRI pro forma for assessment of haemophilia, etc [BLA.001.2164]

12 Extract from GRI medical notes dated 20 October 1965 [BLA.001.2213]

13 Witness statement of Mrs Black [PEN.001.0011]

14 Statement by Counsel to the Inquiry - Day 2, page 69

15 GRI report to GP dated 11 November 1965 [BLA.001.2204]; GRI Haematology form dated 22 October 1965 [BLA.001.2200]. Bottles identified as 3019C; 2727C; AF3097; 3013B without further description. The product was prepared by Cohn fractionation. The process is described in Chapter 20, Haemophilia Therapy - The Period up to the Early 1980s.

16 GRI report to GP dated 11 November 1965 [BLA.001.2204]

17 Letter from GRI to Mr Black dated 23 April 1969 [BLA.001.2154]

18 Dr Colvin - Day 2, page 92

19 Witness statement of Mrs Black [PEN.001.0011]

20 Ibid [PEN.001.0011] at 0012

21 GP request to GRI for out-patient consultation dated 22 March 1971 [BLA.001.2153]

22 At that time a junior doctor in haematology and latterly Director of the Haemophilia Centre at Barts and The London Hospital.

23 Day 2, page 119. Commercial Factor VIII was licensed in the UK in 1972. Until then it was available only for clinical trials and for routine treatment on a named patient basis. Before the Oral Hearings Dr Colvin had not been aware of Mr Black's treatment in the US.

24 Letter from GRI to Dr Pool dated 7 April 1971 [BLA.001.2152]

25 See Chapter 20, Haemophilia Therapy - The Period up to the Early 1980s, paragraphs 20.21-20.22

26 New England Journal of Medicine, 1966; 275:966: letter commenting on use [PEN.018.1455]

27 GP request to GRI for out-patient consultation dated 22 March 1971 [BLA.001.2153]

28 Letter from GRI to Dr Pool dated 07 April 1971 [BLA.001.2152]; letter from GRI to GP dated 9 April 1971 [BLA.001.2151]; and see Mr Black's hospital notes [BLA.001.2218]

29 Letter from GRI to GP dated 9 April 1971 [BLA.001.2151]

30 Letter from GRI to GP dated 3 June 1971 [BLA.001.2149]

31 Letter from GRI to Mr Black dated 7 February 1973 [BLA.001.2146]

32 Letter from GRI to GP dated 22 February 1974 [BLA.001.2145]

33 Letter from GRI to GP dated 30 May 1974 [BLA.001.2142]

34 Letter from GRI to GP dated 17 January 1975 [BLA.001.2139]. The word 'change' in the letter should be read as 'challenge.'

35 Letter from GRI to GP dated 30 June 1975 [BLA.001.2137]; Dr Colvin - Day 2, page 95

36 GRI Haemophilia Centre Treatment Sheet [BLA.001.2231]; Dr Colvin's report [BLA.001.2281] at 2284

37 GRI Haemophilia Centre Treatment Sheet [BLA.001.2231]

38 Letter from GRI to GP dated 22 October 1976 [BLA.001.2135]

39 Letter from GRI to GP dated 26 May 1978 [BLA.001.2134]

40 Letter from GRI to GP dated 9 June 1978 [BLA.001.2133]

41 Letter from GRI to GP dated 6 September 1978 [BLA.001.2132]

42 'Transaminase GOT' is Glutamic-oxaloacetic transaminase, a blood enzyme. GPT (Glutamic-pyruvate transaminase), another blood enzyme, was also elevated. According to Dr Colvin (Day 2, page 97) normal levels for both are about 40. Other 'liver function tests' more frequently referred to in the records are Alanine Aminotransferase (ALT) and Alkaline-phosphotase tests. They have broadly the same significance in the diagnosis of hepatitis.

43 GRI Blood Investigation Sheet [BLA.001.2232]

44 Dr Colvin's report [BLA.001.2281] at 2284

45 Professor Hayes - Day 78, pages 46-48; Professor Hayes' report [PEN.018.0240] at 0240-0241. See Chapters 14-16, Knowledge of Viral Hepatitis 1 to 3.

46 Letter from GRI to GP dated 16 December 1985 [BLA.001.0863]

47 Dr Colvin's report [BLA.001.2281] at 2284

48 Letter from GRI to GP dated 10 April 1981 [BLA.001.0869]

49 Letter from GRI to GP dated 4 September 1984 [BLA.001.0867]

50 Letter from GRI to GP dated 16 December 1985 [BLA.001.0863] Bilirubin and alkaline phosphatise were slightly elevated, while transaminases were markedly elevated.

51 Day 2, pages 99-101

52 Discharge Summary from Lawnwood Regional Medical Center after discharge on 3 October 1987 [BLA.001.0861]

53 Ibid [BLA.001.0861] at 0862

54 Dr Colvin - Day 2, pages 102-103; Dr Bathgate - Day 1, pages 31-32

55 Dr Bathgate - Day 1, pages 31-32; Dr Colvin - Day 2, page 102

56 Witness statement of Mrs Jean Black [PEN.001.0011] at 0012

57 GRI Discharge Report following admission between 14 and 16 October 1987 [BLA.001.0859]; Dr Colvin - Day 2, page 104

58 Dr Colvin's report [BLA.001.2281] at 2284

59 Witness statement of Mrs Jean Black [PEN.001.0011] at 0012. As per statement by Counsel to the Inquiry (Day 2, page 70), Mrs Black confirmed that the word 'sclerosis' in paragraph 7 of her statement should be 'cirrhosed'.

60 Dr Colvin's report [BLA.001.2281] at 2284

61 GRI Discharge Report following admission between 31 October 1987 and 16 November 1987 [BLA.001.0856] at 0857

62 Dr Mutimer's report [BLA.001.2277] at 2277-2278

63 See also Dr Mutimer, Day 1, pages 111-112; Professor Hayes, Day 78, pages 55-56 and Yee et al, 'The Natural History of HCV in a cohort of haemophilic patients infected between 1961 and 1985', Gut, 2000; 47:845-851 [LIT.001.4318] at 4323

64 Dr Mutimer's report [BLA.001.2277] at 2277

65 Chapter 13, Knowledge of Viral Hepatitis Now, paragraphs 13.68-13.69

66 Ibid paragraph 13.71

67 Dr Colvin's report [BLA.001.2281] at 2285; Day 2, pages 113-118

68 GRI Blood Investigation Sheet (HIV -ve on 21 November 1986) [BLA.001.2232]

69 Day 2, pages 111-112

70 Report [BLA.001.2277]

71 Dr Colvin's report [BLA.001.2281] at 2286

72 Dr Colvin - Day 2, pages 111-112

73 Letter from GRI to GP dated 16 December 1985 [BLA.001.0863]

74 GRI Haemophilia Centre Treatment Sheet [BLA.001.2231]

75 Ibid [BLA.001.2231]

76 GRI Haemophilia Centre Treatment Sheet [BLA.001.2230]

77 GRI Haemophilia Centre Home Treatment Sheet [BLA.001.2228]

78 Letter from Haemophilia Unit GRI to Department of Surgery GRI dated 24 September 1991 [BLA.001.0303]

79 'Recombinant Immunoblot Assay'; Regional Virus Laboratory Report dated 14 October1991 [BLA.001.0533]

80 GRI Haemophilia Centre Home Treatment Sheet [BLA.001.2226]

81 GRI Haemophilia Centre Treatment Sheet [BLA.001.2225]

82 Letter from GRI General Medicine to GRI Haemophilia Unit dated 13 April 1994 [BLA.001.0283]

83 Dr Colvin - Day 2, page 109; Dr Colvin's report [BLA.001.2281] at 2285 (para 4.3) and 2286 (para 5.2)

84 Dr Mutimer's report [BLA.001.2277] at 2278

85 Witness statement of Mrs Jean Black [PEN.001.0011] at 0013; Letter from GRI General Medicine to GP dated 3 May 1994 [BLA.001.0281]

86 Dr Mutimer - Day 2, page 125; Letter from GRI General Medicine to GP dated 13 June 1994 [BLA.001.0279]

87 Letter from GRI General Medicine to GP dated 13 June 1994 [BLA.001.0279]

88 Letter from GRI General Medicine to GRI Haemophilia Unit dated 6 April 1995 [BLA.001.0263]

89 Letter from GRI General Medicine to LTU RIE dated 22 May 1995 [BLA.001.0260]

90 Letter from LTU RIE to GRI General Medicine dated 3 July 1995 [BLA.001.1675] at 1676

91 Letter from LTU RIE to GP dated 26 September 1995 [BLA.001.0253]

92 LTU RIE Discharge Summary for GP dated 15 November 1995 [BLA.001.0249]

93 Ibid [BLA.001.0249] at 0250

94 Letter from LTU RIE to GP dated 7 March 1996 [BLA.001.1664]

95 Letter from LTU to Mr Black dated 5 March 1996 [BLA.001.1665]

96 LTU RIE Operation Record dated 21 April 1996 [BLA.001.1646]

97 Discharge Letter from LTU RIE to GP dated 21 May 1996 [BLA.001.1422]

98 Witness statement of Mrs Jean Black [PEN.001.0011] at 0014

99 Pathology Result Enquiry Report dated 25 April 1996 [BLA.001.2289]; Dr Mutimer's report [BLA.001.2277]

100 Letter from LTU RIE to GP dated 30 October 1996 [BLA.001.1453]

101 Letter from LTU RIE to GP dated 18 December 1997 [BLA.001.1451]

102 Letter from LTU RIE to GP dated 7 April 1998 [BLA.001.1442]

103 Letter from LTU RIE to GP dated 12 November 1998 [BLA.001.1583] at 1584

104 Letter from LTU RIE to GP dated 16 February 1999 [BLA.001.1416]

105 Letter from LTU RIE to GP dated 2 June 1999 [BLA.001.1418]

106 Letter from LTU RIE to GP dated 08 February 2001 [BLA.001.1428] at 1429

107 Letter from LTU RIE to GP dated 20 April 2001 [BLA.001.0117]

108 Letter from LTU RIE to GP dated 16 October 2001 [BLA.001.0111]

109 Day 2, pages 134-135; Report [BLA.001.2277] at 2278

110 Letter from LTU RIE to GP dated 27 February 2002 [BLA.001.0108]; Dr Mutimer - Day 2, pages 136-137

111 Letter from LTU RIE to GP dated 30 April 2002 [BLA.001.0106]

112 Letter from LTU RIE to GP dated 10 July 2002 [BLA.001.0102]

113 Letter from LTU RIE to GP dated 30 April 2002 [BLA.001.1248]

114 Letter from LTU RIE to GP dated 13 August 2002 [BLA.001.1244]

115 Ibid [BLA.001.1244]

116 Letter from LTU RIE to GP dated 16 December 2002 [BLA.001.1234]; Dr Mutimer - Day 2, page 138; Report [BLA.001.2277] at 2279

117 Dr Mutimer - Day 2, page 138; Dr Mutimer's report [BLA.001.2277] at 2279

118 Letter from LTU RIE to GP dated 27 January 2003 [BLA.001.0091]

119 Letter from LTU RIE to GP dated 31 January 2003 [BLA.001.0090]; Dr Mutimer's report [BLA.001.2277] at 2279

120 Day 2, page 138. (See Chapter 13, Knowledge of Viral Hepatitis Now, paragraphs 13.97-13.105, on current guidance on treatment for HCV infection.)

121 Letter from LTU RIE to GP dated 4 June 2003 [BLA.001.0079]

122 Letter from LTU RIE to GP dated 10 June 2003 [BLA.001.0078]; Dr Mutimer explained in evidence (Day 2, page 139) that a 'multifocal' tumour is one that has spread with multiple nodules.

123 Dr Mutimer - Day 2, page 139

124 Letter from LTU RIE to GP dated 10 June 2003 [BLA.001.0078]; Dr Mutimer - Day 2, page 140

125 Death Certificate [BLA.001.2118]; Letter from Strathcarron Hospice to GP dated 4 November 2003 [BLA.001.1471]

126 Letter from Surgical Registrar to GP dated 21 May 1996 [BLA.001.1422]

127 Pathology Result Enquiry Report dated 25 April 1996 [BLA.001.2289]

128 LTU RIE Clinical Notes [BLA.001.1760]

129 Discharge letter from LTU RIE to GP dated 21 May 1996 [BLA.001.1422]; LTU RIE Clinical Notes dated 2 to 6 May 1996 [BLA.001.1764]

130 Letter from LTU RIE to GP dated 5 June 1996 [BLA.001.1637]

131 In-Patient Clinical Notes [BLA.001.1768] 'HCC' is a standard abbreviation for hepatocellular cancer.

132 Copy of Report [BLA.001.2289]

133 Dr Bathgate's letter to the CLO dated 13 December 2013 [PEN.019.1446]

134 In Patient Clinical Notes (Surgical) [BLA.001.1773]

135 In Patient Clinical Notes (Surgical) [BLA.001.1774]; 'OLT' and '(P) USS' are understood respectively to be abbreviations for 'Orthotopic Liver Transplant' and 'Planned Ultrasound Scan'.

136 Letter dated 12 November 1998 from LTU RIE to GP [BLA.001.1583] at 1584

137 In Patient Clinical Notes (Surgical) [BLA.001.1774]

138 Letter from RIE to GP dated 22 December 1998 [BLA.001.1436]

139 Ibid [BLA.001.1436]

140 Letter from Transplant Coordinator RIE to GP dated 12 November 1998 [BLA.001.1438]

141 In Patient Clinical Note dated 8 December 1998 [BLA.001.1775]

142 Letter from locum lecturer LTU RIE to GP dated 16 February 1999 [BLA.001.1416]

143 Letter from specialist registrar to GP dated 4 June 2003 [BLA.001.0079]

144 Record Sheet [BLA.001.1430]

145 Dr MacGilchrist's report [PEN.013.1091] at 1092

146 Clinical Record [BLA.001.1737]. 'Nil focal' indicates that no tumour was identified.

147 Dr MacGilchrist's report [PEN.013.1091] at 1092. Alpha fetoprotein is the major protein found in fetal serum (the blood of unborn children). Usually undetectable after birth, its detectable presence in adult blood is a sign of hepatocellular carcinoma.

148 Dr MacGilchrist's report [PEN.013.1091]

149 Day 2, page 147

150 Ibid pages 153-154

151 Dr Colvin's report [BLA.001.2281] at 2285

152 Dr Mutimer's report [BLA.001.2277] at 2278-2279

153 See paragraph 7.41; Dr Mutimer - Day 2, page 135; Report [BLA.001.2277] at 2278

154 Day 2, pages 142-148, 152-154; Supplementary Report [BLA.001.2287] at 2288

155 Supplementary Report [BLA.001.2287] at 2288

156 Mr MacGilchrist's report [PEN.013.1091] at 1092

157 Ibid [PEN.013.1091] at 1092

158 Ibid [PEN.013.1091] at 1093

159 Day 2, pages 137 and 148-149; Letter from RIE to GP dated 30 April 2002 [BLA.001.0106]; Dr Mutimer's supplementary report [BLA.001.2287] at 2288

160 Day 2, page 151

161 Supplementary report [BLA.001.2287]

162 Day 2, pages 147-148

163 Dr Mutimer's supplementary report [BLA.001.2287]; Day 2, pages 149-150.

164 Dr MacGilchrist's report [PEN.013.1091]

165 Ibid [PEN.013.1091] at 1092

166 Ibid [PEN.013.1091] at 1093

167 Dr Mutimer's supplementary report [BLA.001.2287] at 2288

168 Dr Mutimer's report [BLA.001.2277] at 2279

169 Ibid [BLA.001.2277] at 2278

170 Day 2, pages 147-148

171 Ibid pages 150

172 Report [BLA.001.2277] at 2279

173 Report [BLA.001.2281] at 2286

174 Death Certificate [BLA.001.2118]

175 Patient Interest Core Participant closing submissions [PEN.019.0773]

176 Witness Statement of Mrs Kennedy (Mrs O'Hara's daughter) [WIT.003.0420]

177 Death certificate [OHA.001.2641]

178 Dr Mutimer's report [BLA.001.2298]; Letter to GP dated 4 February 1963 [OHA.001.2627]

179 Letter to GP dated 4 February 1963 [OHA.001.2627]

180 Letter to GP from Cardiology clinic [OHA.001.2608]; Mrs Kennedy - Day 3, page 3; Dr Dunn - Day 3, page 109

181 Dr Dunn - Day 3, pages 109-110; Rheumatic fever could also lead to aortic 'incompetence' or leaking.

182 Dr Dunn - Day 3, page 114

183 Ibid page 114

184 Ibid pages 114-115

185 Request for out-patient consultation form dated 1 November 1971 [OHA.001.0899]

186 Haematology Department report dated 30 March 1972 [OHA.001.0881]; see Mrs Kennedy - Day 3, page 22

187 Glasgow Northern Hospitals (Stobhill) Anaesthetic chart dated 31 March 1972 [OHA.001.0430]; Stobhill Haematology Department report dated 30 March 1972 [OHA.001.0881]; Dr Mutimer's report [BLA.001.2298]

188 SNBTS Response to the Inquiry - January 2011 [PEN.001.0032]

189 The Hepatitis C virus was discovered in 1988 and testing was introduced in the UK in 1991.

190 SNBTS Response to the Inquiry - January 2011 [PEN.001.0032]

191 Day 3, page 25; Recovery room chart [OHA.001.0076]; Haematology Department Form [OHA.001.0738]

192 SNBTS Response to the Inquiry - January 2011 [PEN.001.0032]

193 Letter from Stobhill to GP dated 21 February 1984 [OHA.001.2565]

194 Dr Dunn - Day 3, page 116

195 Ibid page 117

196 Dr Mutimer's report [BLA.001.2298] at 2299

197 Explanation by Counsel to the Inquiry - Day 3, page 22; GRI Report form dated 1 July 1985 [OHA.001.2554]; GRI operation report dated 7 June 1985 [OHA.001.2555];

198 Explanation by Counsel to Inquiry - Day 3, page 20; Blood bank form [OHA.001.1303]

199 Blood loss/replacement chart [OHA.001.1425]

200 I.V. Therapy Prescription sheet [OHA.001.1428]

201 SNBTS Response to the Inquiry [PEN.001.0032] at 0033. See paragraph 7.211.

202 Letter from Stobhill to GP dated 10 May 1990 [OHA.001.2539]; Mrs O'Hara was later treated with insulin for Type II diabetes.

203 Referral letter [OHA.001.2543]

204 Letter to GP dated 10 May 1990 [OHA.001.2539]

205 Letter [OHA.001.1178]

206 Ibid [OHA.001.1178]; Witness Statement of Mrs Kennedy [WIT.003.0420] at 0421

207 Witness Statement of Mrs Kennedy [WIT.003.0420] at 0421

208 Ibid

209 Letter to the GRI [OHA.001.1178]

210 Letter to GP [OHA.001.2538]

211 Letter dated 6 September 1990 [OHA.001.2536]

212 Letter to GP [OHA.001.2535]

213 Ibid [OHA.001.2535]

214 Letter to GP [OHA.001.1172]

215 Test results [OHA.001.1276]; [OHA.001.1273]

216 Test results [OHA.001.1275]; [OHA.001.1273]

217 Test results [OHA.001.1274]

218 Test results [OHA.001.1272]

219 Letter to Mrs O'Hara [OHA.001.1171]

220 File note dated 17 January 1991 [OHA.001.1162]: Mrs O'Hara's recollection was that she attended the Urology Clinic, but in fact she was seen by Dr Morris.

221 Referral letter [OHA.001.1168]

222 Letter to Dr Lorimer dated 18 January 1991 [OHA.001.1167]

223 Letter to GP [OHA.001.1160]

224 GRI discharge report dated 3 April 1991 [OHA.001.1155]

225 Ibid [OHA.001.1155] at 1156

226 Letter [OHA.001.1146]

227 Letter dated 11 March 1991 [OHA.001.2529]

228 Letter to GP [OHA.001.1153]; GRI discharge report dated 3 April 1991 [OHA.001.2527]

229 Letter to the GRI [OHA.001.1152]

230 Discharge letter from the GRI to GP dated 5 August 1991 [OHA.001.1151]

231 Letter [OHA.001.1154]. At this stage it was known that the operation would be delayed until after a family wedding at the beginning of October.

232 GRI discharge report [OHA.001.2520]

233 Letter from GRI to GP dated 17 December 1991 [OHA.001.1138]

234 Letter from GRI to GP dated 16 February 1993 [OHA.001.1137]

235 Letter from GRI to GP dated 27 February 1994 [OHA.001.1136]

236 Letter from Stobhill to GP dated 5 August 1994 [OHA.001.2502]

237 Letter from Stobhill to GRI [OHA.001.1135]

238 Letter from GRI to Stobhill dated 11 August 1994 [OHA.001.1134]

239 Letter [OHA.001.2501]

240 Letter to GP [OHA.001.2496]

241 Letter to GP [OHA.001.2500]

242 Letter to GP dated 26 October 1994 [OHA.001.2494]

243 Letter [OHA.001.2493]; GRI discharge report dated 3 April 1991 [OHA.001.1155]

244 Letter from Stobhill dated 5 January 1995 [OHA.001.2486]

245 Dr Mutimer - Day 3, page 42

246 The implication of the comment appears to be that if right heart failure had been the cause of the enlarged liver and spleen in 1990, the abnormalities would have disappeared following the successful operation.

247 Letter from Stobhill dated 5 January 1995 [OHA.001.2486]

248 Dr Dunn - Day 3, pages 117-118

249 Dr Mutimer - Day 3, pages 42-43

250 Dr Dunn - Day 3, page 118

251 Regional Virus Laboratory test results dated 8 February 1995 [OHA.001.0834]

252 Dr Mutimer - Day 3, page 44

253 Regional Virus Laboratory PCR test results dated 3 April 2003 [OHA.001.2710]

254 Letter from Stobhill to GP dated 9 March 1995 [OHA.001.2476]

255 Dr Mutimer - Day 3, page 45; letter from Stobhill to GP dated 9 March 1995 [OHA.001.2476]

256 Dr Mutimer - Day 3, page 46

257 Letter from Stobhill to GP [OHA.001.2475]

258 Letter [OHA.001.2474]

259 Dr Mutimer - Day 3, page 47

260 Letter [OHA.001.2473]

261 Dr Dunn - Day 3, pages 119-120

262 Letter from Stobhill to GP dated 02 August 1995 [OHA.001.2469]

263 Dr Mutimer - Day 3, pages 51-52

264 Letter from Stobhill to GP dated 02 August 1995 [OHA.001.2469]

265 Letter from Stobhill to GP dated 12 September 1995 [OHA.001.2468]; Dr Mutimer - Day 3, page 52

266 Dr Mutimer - Day 3, page 52

267 Letter from Stobhill to GP dated 02 August 1995 [OHA.001.2469]

268 Witness Statement of Mrs Kennedy [WIT.003.0420] at 0421 and 0422

269 Ibid [WIT.003.0420] at 0424

270 GP's clinical notes [OHA.001.2287] at 2287-89

271 Ibid [OHA.001.2287] at 2288

272 Letter from Stobhill to GP dated 12 September 1995 [OHA.001.2468]

273 Letter from Dr Prasad to Dr Forrest both Stobhill dated 12 September 1995 [OHA.001.1011]. (This letter was dictated 11 September but typed and presumably sent on 12 September 1995 rather than on 12 May 1995 which appears to be a typographical error).

274 Letter from Stobhill to GP dated 12 September 1995 [OHA.001.2468]

275 Letter to Dr Dunn [OHA.001.1003]

276 Letter from Stobhill to GP dated 16 January 1996 [OHA.001.2464]

277 Dr Dunn - Day 3, pages 120-123

278 Ibid pages 122-123

279 Letter from Stobhill Cardiology to Dr Forrest dated 11 March 1996 [OHA.001.1008]

280 Letter from Stobhill General Medicine to Dr Forrest dated 09 May 1996 [OHA.001.1012]

281 Letter from Stobhill Cardiology to GP dated 12 July 1996 [OHA.001.1013]

282 Letter from Dr Forrest to Dr McLaren, both Stobhill [OHA.001.1017]

283 Letter from Dr McLaren to Mrs O'Hara dated 24 July 1996 [OHA.001.1020]; Letter from Dr McLaren to Dr Forrest, copied to GP, dated 24 July 1996 [OHA.001.1019]

284 Letter from Stobhill to GP dated 23 April 1997 [OHA.001.2439/40]

285 Dr Mutimer - Day 3, pages 63-64

286 Ibid page 64

287 Stobhill surgeon's notes [OHA.001.1045]

288 Letter from Stobhill Haematology to GP [OHA.001.1049]

289 Dr Mutimer - Day 3, pages 64-65

290 Letter from Stobhill to GP dated 14 June 1999 [OHA.001.1083]

291 Dr Dunn - Day 3, pages 123-124

292 Letter from Stobhill to GP dated 18 October 2001 [OHA.001.2184]

293 Dr Dunn - Day 3, pages 125-126

294 Letter from Stobhill to GP dated 09 May 2002 (dictated on 13 March 2002) [OHA.001.1112]

295 Dr Dunn - Day 3, pages 126-127

296 Letter from Stobhill to GP dated 09 May 2002 (dictated on 13 March 2002) [OHA.001.1112]. The medication listed included 'Humulin'.

297 Witness Statement of Mrs Kennedy [WIT.003.0420] at 0424

298 Letter from GP to Stobhill dated 24 March 2003 (see handwritten note dated 26 March 2003 on page 2) [OHA.001.2156]

299 Ibid [OHA.001.2156]

300 Polymerase Chain Reaction test (see Glossary).

301 Dr Mutimer - Day 3, page 45; Test result [OHA.001.2710]

302 Stobhill Diagnostic Imaging Report dated 31 March 2003 [OHA.001.0844]

303 Dr Mutimer- Day 3, page 68; Dr Mutimer's Report [BLA.001.2298] at 2300

304 Dr Mutimer - Day 3, pages 66-67

305 Ibid pages 68-69

306 Letter from Stobhill to GP dated 15 May 2003 [OHA.001.1451]

307 Dr Robertson - Day 3, page 93

308 Ibid

309 Letter from Stobhill to GP dated 15 May 2003 [OHA.001.1451]

310 Dr Robertson - Day 3, page 94: 'ERCP' is Endoscopic Retrograde Cholangiopancreatography (see Glossary).

311 Day 3, pages 96-98

312 Dr Robertson - Day 3, page 98

313 Stobhill surgeon's notes dated 07 April 2003 [OHA.001.1455]

314 Dr Robertson - Day 3, page 99; Stobhill surgeon's notes dated 10 April 2003 [OHA.001.1454]

315 Dr Robertson - Day 3, page 100

316 Stobhill surgeon's notes dated 18 April 2003 [OHA.001.1453]

317 Dr Robertson - Day 3, pages 100-101

318 'Decompensation' is a failing condition of an organ, such as the liver.

319 Letter from Stobhill to GP dated 15 May 2003 [OHA.001.1451]

320 Dr Robertson - Day 3, page 103; Dr Robertson's report [PEN.010.0170] at 1071; Dr Petrie's letter to CLO dated 23 February 2011 [PEN.010.0182]

321 Dr Robertson's report [PEN.010.0170] at 0172; Dr Robertson - Day 3, page 106

322 Dr Mutimer - Day 3, pages 68-69

323 Death certificate [OHA.001.2641] - the death certificate was signed by Dr Petrie; Email from Dr Petrie dated 24 February 2011 [PEN.010.0157]

324 Witness statement of Mrs Kennedy [WIT.003.0420] at 0425

325 Day 3, page 79

326 Ibid page 79

327 Ibid pages 79-80

328 Ibid pages 83-84

329 Ibid page 80

330 Ibid pages 70-74

331 Ibid Pages 75-76

332 Bilirubin is a product of the red blood cells of the body, formed from broken-down haemoglobin. See Chapter 13, Knowledge of Viral Hepatitis Now, paragraphs 13.55-13.56

333 Day 3, pages 74-75

334 Ibid pages 70 and 73

335 Ibid page 72

336 Ibid page 85

337 Dr Robertson - Day 3, pages 104-105

338 Report [PEN.010.0182]

339 Day 3, pages 129-130

340 Ibid pages 132-133

341 Dr Dunn - Day 3, page 134

342 Ibid page 131

343 Ibid pages 131-132

344 Ibid pages 32 and 81; Dr Mutimer's report [BLA.001.2298] at 2301

345 Test results [OHA.001.1272]

346 Enzyme-linked Immunosorbent assay; letter from Dr Cameron dated 03 December 2010 [PEN.001.0025]

347 A brief explanation is given by Dr Dow - Day 4 pages 58-59. The topic is discussed in detail in his report [PEN.001.0016] and in the report of Mr Laing's death. See also: Chapter 16, Knowledge of Viral Hepatitis 3 - 1986 Onwards, paragraphs 16.31 and 16.47.

348 Explained by Counsel to the Inquiry Day 3, page 33.

349 Day 3, page 81

350 Mrs Kennedy - Day 3, page 3

351 Day 3, pages 82-83

352 Ibid page 113

353 Closing submissions of patient interest core participants (para 5) [PEN.019.0779] at 0781

354 See paragraph 7.110

355 Letter to GP [OHA.001.1173]

356 Dr Morris' referral letter [OHA.001.1168]

357 Day 3, pages 30-31

358 Ibid pages 32-33; Report [BLA.001.2298] at 2301

359 Ibid pages 48-49

360 Dr Morris' letter to Dr Lorimer [OHA.001.1168]

361 Day 3, pages 34 and 51

362 Details of the developing picture are given in the Preliminary Report at paragraphs 9.163, 9.167, 9.186, 9.235 and 236, 9.245 and 9.284, and are discussed in this report in Chapter 31, The Introduction of Screening of Donated Blood for Hepatitis C.

363 Enzyme-linked mmunosorbent Assay.

364 Recombinant Immunoblot Assay.

365 Test result [OHA.001.1272]

366 Letter from Dr Cameron dated 03 December 2010 [PEN.001.0025]

367 Dow et al, 'SNBTS Evaluation of the Ortho HCV Antibody ELISA Test System', 13 December 1989 [SNF.001.1180] at 1209

368 Day 3, page 37

369 Whether, following the negative Hepatitis C result in 1990, and against the background of findings of abnormal LFTs, Mrs O'Hara's liver condition should have continued to be monitored by Gastroenterology: paragraph 7.173

370 Day 3 pages 49-50

371 Ibid pages 48-49

372 Ibid page 51

373 GP Records [OHA.001.2291]; Test report [OHA.001.2329]

374 [OHA.001.2088] at 2289. The exception relating to Gamma GT is insignificant for this purpose.

375 Letter from Dr Morris to GP dated 05 November 1990 [OHA.001.2535]; discussed at paragraph 7.104

376 Day 3, page 34

377 Ibid pages 38-39

378 Ibid page 39

379 Ibid pages 38-39

380 Letter from Dr McLaren, Stobhill to GRI dated 05 August 1994 [OHA.001.1135]; discussed at paragraph 7.114 above.

381 Day 3, page 46

382 Ibid pages 47-48

383 Dr Forrest's letter [OHA.001.1003]

384 Letter from Dr Forrest to Dr McLaren [OHA.001.1017]

385 Day 3, page 55; Dr Mutimer's report [BLA.001.2298] at 2299-2301

386 Dr Mutimer's report [BLA.001.2298] at 2300; Day 3, page 57

387 Day 3, pages 56-57

388 Dr Mutimer - Day 3, page 57

389 Ibid page 57

390 Letter from Dr Forrest to Dr McLaren dated 10 July 1996 [OHA.001.1017] at 1018

391 Day 3, page 60

392 Dr Mutimer - Day 3, page 61

393 Ibid pages 58-59

394 Witness Statement of Mrs Kennedy [WIT.003.0420] at 0422; Letter from Dr Forrest's SHO to Stobhill Urology dated 15 November 1994 [OHA.001.0978], although concerning another matter, includes the comment: 'Mrs O'Hara's daughter is a staff nurse ... at Stobhill & obviously very anxious'.

395 Mrs Kennedy - Day 3, page 5; The doctor cannot be identified. This was probably an informal meeting and was not recorded at the time, so far as Stobhill's records show.

396 Mrs Kennedy - Day 3, page 15

397 Day 3, pages 61-62

398 Dr Mutimer - Day 3, page 62; Mrs Kennedy - Day 3, pages 5 and 7; Witness Statement of Mrs Kennedy [WIT.003.0420] at 0422

399 Dr Mutimer Day 3, page 78

400 Closing submissions of patient interest core participants (para 6.1) [PEN.019.0779] at 0781

401 Transfusion-transmitted Hepatitis C Guidelines [LAI.001.0020]

402 Mrs Kennedy - Day 3, pages 9-12

403 Ibid page 7

404 Witness Statement of Mrs Kennedy, para 12 [WIT.003.0420] at 0423

405 Mrs Kennedy - Day 3, pages 5-6

406 Witness Statement of Mrs Kennedy [WIT.003.0420] at 0422

407 Ibid [WIT.003.0420] at 0422

408 Ibid [WIT.003.0420] at 0423

409 Day 3, page 7

410 Letter from Stobhill to GP dated 23 April 1998 [OHA.001.2249]

411 Dr Mutimer - Day 3, pages 65-66

412 Explanation by Inquiry Counsel - Day 1, pages 143-150; Letter from Inquiry to Susan Murray, Central Legal Office dated 10 December 2010 [PEN.010.0074]; SNBTS response - January 2011 [PEN.001.0032] at 0033; Email from Inquiry to CLO dated 03 February 2011 [PEN.002.0762]; SNBTS Supplementary response - February 2011 [PEN.002.0760]

413 Letter from Dr Rachel Green, NHS Greater Glasgow and Clyde Acute Services Division to CLO dated 25 August 2011 [PEN.017.2153]

414 Letter from Dr Tait, GRI Haematology to Dr Rachel Green dated 25 November 2008 [PEN.010.0106]

415 Typically a free text box.

416 Closing submissions of patient interest core participants (para 3) [PEN.019.0779]

417 Death Certificate [LAI.001.1068]

418 Witness Statement of Mrs Annie Laing [WIT.003.0417]

419 Dr Alexander - Day 4, page 42

420 Letter from ARI to GP dated 20 August 1990 [LAI.001.0127]

421 Dr Alexander - Day 4, page 8

422 Witness Statement of Mrs Annie Laing [WIT.003.0417]

423 ARI Record sheet dated 7 August 1990 [LAI.001.0829]; Letter from Aberdeen and North East Scotland BTS (SNBTS) to GP dated 26 April 1995 [LAI.001.0105]; Dr Alexander - Day 4, pages 8-9

424 Mr Laing was so told by his surgeon at ARI, according to witness statement of Mrs Annie Laing [WIT.003.0417] and/or by his GP according to letter from the GP to him dated 6 June 1995 [LAI.001.0102]

425 Letter from Aberdeen and North East Scotland BTS (SNBTS) to GP dated 26 April 1995 [LAI.001.0105]; Assessment form [LAI.001.0103]

426 Dr Alexander - Day 4, pages 9-10

427 Ibid page 45

428 Ibid page 44

429 See Chapter 18, Collection of Blood - General and Chapter 26, Donor Selection - Higher Risk Donors for more detail.

430 Dr Alexander - Day 4, pages 44-45

431 Dr Dow's report [PEN.012.0344] at 0345

432 It was explained by Professor Turner that, in blood donation circles, the expression 'deferral' is used rather than 'rejection' - Day 7, page 16

433 Professor Turner - Day 7, pages 16-20; Witness Statement of Professor Turner [PEN.002.0452] at 0454

434 Dr Alexander - Day 4, page 10

435 Ibid pages 9-14

436 Ibid pages 11-12

437 Letter from Aberdeen and North East Scotland BTS (SNBTS) to GP dated 31 May1995 [LAI.001.0019]; Counselling Guidelines [LAI.001.0020]; Form to document outcome of counselling (complete version) [PEN.017.2267-69]

438 Letter from GP to Mr Laing [LAI.001.0102]

439 Letter from GP to Mr Laing [LAI.001.0101]

440 Letter from GP to Dr Yates dated 30 June 1995 [LAI.001.0100]

441 Dr Alexander - Day 4, page 13

442 Ibid page 14; GP Request for hospital care form dated 12 July 1995 [LAI.001.0098]

443 Letter from ARI to GP dated 24 August 1995 [LAI.001.0095]

444 Dr Alexander - Day 4, page 16

445 Letter from ARI to GP dated 24 August 1995 [LAI.001.0095]

446 Dr Alexander - Day 4, page 17

447 Ibid pages 17-18

448 Ibid page 17

449 Letter from ARI to GP dated 17 November 1995 [LAI.001.0092]

450 Day 4, page 17

451 Letter from ARI to GP dated 17 November 1995 [LAI.001.0092]

452 ARI Histopathology report dated 30 January 1996 [LAI.001.1009]; Dr Alexander's report [LAI.001.1125] at 1126

453 Day 4, pages 19-21

454 Ibid page 22

455 ARI handwritten note dated 2 May 1996 [LAI.001.0625]; Letter from ARI to GP dated 15 May 1996 [LAI.001.0087]; Dr Sinclair's report [PEN.010.0174]

456 Day 4, pages 39-40

457 Letter from ARI to GP dated 15 May 1996 [LAI.001.0087]

458 Day 4, page 40; Report [LAI.001.1125] at 1127

459 Ibid page 21

460 Ibid page 40; Report [LAI.001.1125] at 1128

461 Letter from ARI to GP dated 11 April 1996 [LAI.001.0088]

462 Letter from ARI to GP dated 7 October 1996 [LAI.001.0083]

463 Day 4, pages 23 and 40; Report [LAI.001.1125] at 1127

464 Witness Statement of Mrs Annie Laing [WIT.003.0417] at 0418

465 GP request for appointment form dated 4 September 2000 [LAI.001.0067]

466 Day 4, page 24

467 Ibid page 25

468 Witness Statement of Mrs Annie Laing [WIT.003.0417] at 0418

469 Letter from ARI to GP dated 21 December 2001 [LAI.001.0057] at 0058

470 Ibid [LAI.001.0057] at 0058; GP request for appointment dated 31 December 2001 [LAI.001.0055]

471 Day 4, page 26

472 Letter from GP to Mr Laing dated 31 December 2001 [LAI.001.0056] and Request by GP for outpatient appointment [LAI.001.0055]

473 Witness Statement of Mrs Annie Laing [WIT.003.0417] at 0418

474 Medical records dated 14 and 15 January 2002 [LAI.001.0183]; 28 January and 1 March 2002 [LAI.001.0182]

475 Reports [LAI.001.0202] and [LAI.001.0210]

476 Referral letter [LAI.001.0044] and [LAI.001.0045]

477 Letter from ARI to GP [LAI.001.0043]

478 Letter from ARI to GP [LAI.001.0041]

479 Witness Statement of Mrs Annie Laing [WIT.003.0417] at 0418 and 0419. Mrs Laing says that this occurred on 2 June. The medical records indicate it was on 6 June [LAI.001.0177]

480 Medical records [LAI.001.0177] and [LAI.001.0178]

481 Referral letter dated 16 June 2003 [LAI.001.0038]

482 Letter from Woolmanhill Hospital to GP dated 2 July 2003 [LAI.001.0037]

483 Referral letter from GP to Woolmanhill Hospital dated 16 June 2003 [LAI.001.0038] at 0039

484 Dr Alexander - Day 4, page 26; Letter from ARI to GP dated 19 July 2002 [LAI.001.0050] The letter was dictated on 18 June.

485 Day 4, pages 27-28

486 Ibid page 29

487 Ibid pages 26-27

488 Letter from Woolmanhill Hospital to GP dated 2 July 2003 [LAI.001.0037]; Letter from ARI to GP dated 6 August 2003 [LAI.001.0032]; Witness Statement of Annie Laing [WIT.003.0417] at 0419

489 ARI Diagnostic Imaging report dated 24 July 2003 [LAI.001.1020]

490 Day 4, pages 29-30

491 Letter from ARI to GP dated 12 September 2003 [LAI.001.0031]

492 'Decompensation' is the failing condition of an organ, such as the liver.

493 Dr Alexander - Day 4, page 31

494 Letter from ARI to GP dated 12 September 2003 [LAI.001.0031]

495 Death Certificate [LAI.001.1068]

496 Day 4, pages 32-33

497 Day 4, pages 34-35

498 Ibid pages 36-37

499 Ibid pages 42-44 and 46-47

500 Ibid pages 42-44 and 46-47

501 See Chapter 13, Knowledge of Viral Hepatitis Now and Chapter 16, Knowledge of Viral Hepatitis 3 - 1986 Onwards

502 Dr Dow - Day 4, pages 54-61

503 Ibid pages 85-86

504 Ibid pages 62-64

505 Ibid pages 58-59

506 Ibid page 78

507 Ibid page 53; Dr Dow's amended report [PEN.012.0344]

508 Now retired, Dr Dow was Consultant Clinical Microbiologist of the SNBTS Microbiology Unit, Glasgow. In 1992, he was Principal Clinical Scientist of the Microbiology Unit.

509 Dr Dow - Day 4, page 65; The research project was reported in 1993: McOmish et al, 'Detection of three types of hepatitis C virus in blood donors', Transfusion, 1993; 33, [PEN.001.0018]

510 Dr Dow - Day 4, page 65

511 A surrogate marker is a directly measurable physical entity (usually measured in a blood test) that correlates (has a statistical association) with a disease where it is not possible to test directly for the disease or where any direct test would be problematic. See Chapter 27, Surrogate Testing of Donated Blood for non-A, non-B Hepatitis for more detailed discussion.

512 Dr Dow - Day 4, pages 67-68

513 Dr Dow - Day 4, pages 70-71; Dr Dow's amended report [PEN.012.0344] at 0345

514 Ibid page 70

515 Dr Dow's amended report [PEN.012.0344] at 0345

516 Closing Submission [PEN.019.0777]

517 Day 4, page 42

518 Report on Alexander Black Laing [LAI.001.1125] at 1127-1128

519 Closing Submission [PEN.019.0777]

520 Death certificate [TAM.001.2946]

521 Letter from Deputy Crown Agent to the Inquiry dated 22 December 2010 [PEN.001.0303]

522 Ibid

523 Ibid Letter from Central Legal Office to Inquiry dated 23 November 2010 [PEN.001.0246]; Letter from Practitioner Services to CLO dated 11 November 2009 [PEN.001.0245]

524, last accessed 08/01/15

525 Letter from Deputy Crown Agent to the Inquiry dated 22 December 2010 [PEN.001.0303]

526 Ibid [PEN.001.0303]

527 Ibid [PEN.001.0303]

528 Summary of records [TAM.001.1459]

529 See paragraph 7.302

530 Witness Statement of Mrs Jean Tamburrini [PEN.001.0309]

531 Ibid [PEN.001.0309] at 0310; Affidavit of Bernard Fisher [PEN.018.1559]; Mrs Jean Tamburrini - Day 1, pages 14-15

532 Witness Statement of Mrs Jean Tamburrini [PEN.001.0309] at 0310

533 GP's request to the GRI for out-patient consultation dated 2 June 1998 [TAM.001.2583]

534 Letter from the GRI to GP dated 17 July 1998 [TAM.001.2582]

535 GRI careplan [TAM.001.2907]

536 Letter from the GRI to GP dated 20 January 1999 [TAM.001.2574]

537 Letter from the GRI to GP dated 3 March 1999 [TAM.001.2572]

538 Letter from the GRI to GP dated 5 March 1999 [TAM.001.2573]

539 Witness Statement of Mrs Jean Tamburrini [PEN.001.0309] at 0311

540 Letter from the Glasgow Dental Hospital to the GRI dated 18 June 2001 [TAM.001.2540]; Letter from GP to the GRI dated 8 June 2001 [TAM.001.2570]

541 Letter from the GRI to the Glasgow Dental Hospital dated 8 August 2001 [TAM.001.2542]

542 'Thrombocytopenia' refers to a shortage of platelets. The letter referred to 'thrombocytosis' and was corrected by Dr Mutimer. Eosinophilia and reticulocytosis refer to the replacement of red cells by the bone marrow: Day 1, page 97

543 Day 1, pages 96-97

544 Ibid page 96

545 Dr Mutimer - Day 1, page 97

546 Letter from the GRI to GP dated 31 October 2001 [TAM.001.2553]

547 'Polymerase Chain Reaction' test (see Glossary); Regional Virus Laboratory Test result form dated 12 September 2001 [TAM.001.2703]

548 Witness Statement of Mrs Jean Tamburrini [PEN.001.0309] at 0311

549 Ibid at 0312

550 Letter from the GRI to GP dated 28 October 2001 [TAM.001.2559]

551 Dr Mutimer's report [PEN.010.0310] at 0311

552 Ibid at 0313

553 Letter from the GRI to GP dated 9 December 2001 [TAM.001.2557]; Letter from the GRI to the RIE dated 14 February 2002 [TAM.001.2565]

554 Summary of GP records printed on 6 January 2005 [TAM.001.1459] at 1460

555 eg GRI careplan dated 10 December 1998 [TAM.001.2907]

556 Professor van Aken - Day 2, page 20

557 Ibid

558 GRI IV therapy prescription sheet [TAM.001.2462]; Dr Cuthbertson - Day 1, page 123; Joint statement of Drs Perry and Cuthbertson on SPPS Batch No 1194 dated 4 March 2011 [PEN.011.0048] at 0051

559 Professor van Aken - Day 2, pages 20-22

560 Letter from the GRI to GP dated 10 October 1984 [TAM.001.2591]

561 Excerpt from the BP (referred to as Plasma Protein Fraction) [PEN.001.0259]; Statement of Drs Perry and Cuthbertson on SPPS Batch No 1194 dated 4 March 2011 [PEN.011.0048] at 0049

562 Dr Cuthbertson - Day 1, page 123 et seq

563 Excerpt from the BP [PEN.001.0259]

564 SNBTS record for SPPS Batch No 1194 [PEN.001.0260]

565 Statement of Drs Perry and Cuthbertson on SPPS Batch No 1194 dated 4 March 2011 [PEN.011.0048]

566 Day 1, page 121 et seq; Statement of Drs Perry and Cuthbertson on SPPS Batch No 1194 dated 4 March 2011 [PEN.011.0048]

567 Dr Cuthbertson - Day 1, page 123

568 Excerpt from the BP [PEN.001.0259]

569 Dr Cuthbertson - Day 1, page 132

570 Ibid page 133

571 Ibid page 133; Pattison et al,' An outbreak of Type B Hepatitis associated with transfusion of Plasma Protein Fraction', American Journal of Epidemiology, 1976; 103/4:99[LIT.001.3122]

572 Ibid [LIT.001.3122] at 3127; Dr Cuthbertson - Day 1, page 133

573 Day 2, pages 47-49

574 Dr Cuthbertson - Day 1, page 134

575 Professor van Aken - Day 2, page 49; Report [PEN.001.0306] at 0307

576 Dr Cuthbertson - Day 1, page 133

577 Professor van Aken - Day 2, pages 27-28; Excerpt from the BP [PEN.001.0259]

578 Dr Cuthbertson - Day 1, pages 133 and 138

579 Ibid Day 1, pages 135-138; Statement of Drs Perry and Cuthbertson on SPPS Batch No 1194 dated 4 March 2011 [PEN.011.0048]

580 Day 2, pages 35-36 and 38

581 Ibid page 36; Yei et al, 'Partitioning of hepatitis C virus during Cohn-Oncley fractionation of plasma', Transfusion, 1992; 32/9:824-828) [LIT.001.3218]; Scheiblauer et al, 'Prevalence of Hepatitis C virus in plasma pools and the effectiveness of cold ethanol fractionation', Clinical Therapeutics, 1996; 18/B:59-70) [LIT.001.3131]

582 Day 2, pages 36-37 and 40

583 Erstad, 'Viral infectivity of albumin and plasma protein fraction', Pharmacotherapy, 1996; 16/6:996-1000) [LIT.001.3117]

584 Professor van Aken's report [PEN.001.0306] at 0307

585 Day 2, pages 44-45; Professor van Aken's report [PEN.001.0306] at 0308

586 Day 1, pages 126-130; SNBTS record for SPPS Batch No 1194 [PEN.001.0260]

587 Day 1, page 129

588 Dr Cuthbertson - Day 1, pages 135-139

589 Ibid page 131

590 Ibid pages 139-140

591 Ibid pages 141-144

592 Professor van Aken's report [PEN.001.0306]; Professor van Aken - Day 2, pages 26-53

593 'Guidelines on viral inactivation and removal procedures intended to assure the viral safety of human blood plasma products', Annex 4 to WHO Technical Report, Series No. 924, 2004 [LIT.001.3143]

594 Professor van Aken's report [PEN.001.0306] at 0308

595 Professor van Aken - Day 2, page 53

596 Ibid

597 Dr Mutimer - Day 1, page 110; Dr Mutimer's report [PEN.010.0310] at 0313 and 0315

598 Medicine Inspectorate 1981 Report [SNB.005.6826]; Medicine Inspectorate 1988 Report (draft only) [SNB.008.8791]

599 Letter from Thompsons to Inquiry Solicitor dated 24 February 2011 [PEN.010.0386]

600 Professor van Aken's supplementary report [PEN.011.0001]; Day 2, pages 56-57

601 Ibid Day 2, pages 54-56

602 Day 2, pages 54-55

603 Professor van Aken's Supplementary report [PEN.011.0001]

604 As set out in statement of Drs Perry and Cuthbertson SPPS Batch No 1194 dated 4 March 2011 [PEN.011.0048]

605 Professor van Aken - Day 2, pages 56-57 and 60-62

606 Day 2, page 59

607 Ibid pages 59-60; Dr Cuthbertson - Day 1, pages 141-142

608 Day 2, pages 63-64

609 Ibid page 65

610 Professor van Aken - Day 2, pages 65-67

611 Dr Mutimer's report [PEN.010.0310] at 0311

612 GRI careplan [TAM.001.2907]

613 GRI IV Therapy prescription sheet [TAM.001.2918]; GRI blood bank record [TAM.001.2463]

614 Medical notes from 15 December 1998 [TAM.001.2912]; Discharge letter from the GRI to GP dated 20 January 1999 [TAM.001.2574]

615 Day 1, pages 74-75; Report [TAM.001.2380] at 2388

616 GP's request to the GRI for out-patient consultation dated 2 June 1998 [TAM.001.2583]

617 Dr Mutimer - Day 1, page 110

618 Day 2, pages 3 and 7-10

619 Ibid page 10

620 Dr Peterkin's letter to Dr Walker [TAM.001.2396]

621 Day 2, page 3

622 GRI blood bank record [TAM.001.2463]; GRI IV Therapy prescription sheet [TAM.001.2918]; Day 2, pages 5-7

623 Day 2, pages 7-9

624 Ibid pages 9-10

625 Day 1, page 114

626 Ibid page 113

627 Patient interest core participant's closing submissions [PEN.019.0783] at 0785

628 Dr Mutimer's Report [PEN.010.0310] at 0311; Letter from the GRI to GP dated 13 December 2001 [TAM.001.2564]

629 Dr Mutimer - Day 1, page 111

630 Ibid page 112

631 Letter from the GRI to GP dated 13 December 2001 [TAM.001.2564]

632 Day 52, pages 17-18. The evidence of a relationship between alcohol consumption and Hepatitis C progression is discussed in Chapter 13, Knowledge of Viral Hepatitis Now, at paragraphs 13.75-13.81.

633 Freeman et al, ' Estimating progression to cirrhosis in chronic Hepatitis C virus infection,' Hepatology, 2001; 34:809-816) [LIT.001.4365]

634 Evidence of Professor Thomas - Day 53, pages 42-43. The synergism of alcohol was discovered as a result of work on the 'Replicon' model of Hepatitis C by Bartenschlager.

635 SIGN Guideline 2006 (paragraph 8.4) [PEN.018.0298] at 0317; SIGN Guideline 2013 ( paragraph 9.4) [LIT.001.5550] at 5574

636 Summary of GP Records 1968-2004 [TAM.001.1459] at 1460

637 Letter from the GRI to the Glasgow Dental Hospital dated 8 August 2001 [TAM.001.2542]. See also Dr McLintock's letter to the GRI Gastroenterology dated 20 September 2001 which reported similar consumption [TAM.001.2545]

638 Letter from the GRI to GP dated 31 October 2001 [TAM.001.2553]

639 Letter from the GRI to GP dated 9 December 2001 [TAM.001.2557]

640 Ibid at 2558

641 Letter from the GRI to GP dated 15 January 2002 [TAM.001.2562]

642 Letter from the GRI to the RIE LTU dated 14 February 2002 [TAM.001.2565]

643 Letter from the GRI to GP dated 15 February 2002 [TAM.001.2566]

644 Letter from the RIE LTU to GP [TAM.001.2524]

645 Ibid [TAM.001.2524]

646 Letter from the RIE to the Parkhead Hospital, Glasgow dated 6 March 2002 [TAM.001.0905]

647 Letter from the Community Alcohol Service to the RIE dated 10 April 2002 [TAM.001.0898]. The Community Alcohol Service details form [TAM.001.3074] at 3097. Efforts by the Inquiry team to trace Audrey Ewing (Russell) to obtain her evidence were unsuccessful, as set out in the transcript of Day 1, pages 82-83.

648 Letter from the Community Alcohol Service to the RIE dated 9 May 2002 [TAM.001.0897]

649 Letter from the Community Alcohol Service to the RIE dated 12 August 2002 [TAM.001.3076]

650 Dr McCallum's letter [TAM.001.0905]

651 Dr Mutimer's report [PEN.010.0310] at 0313

652 The psychological assessment carried out by Dr McCallum [TAM.001.0905] refers to 50-100 units per week and to 'drinking to excess over the last 5 years'. The reference to drinking 100 units a week over eight years is in the letter from Dr MacGilchrist's registrar dated 5 March 2002 [TAM.001.2524]. Dr Mutimer has conflated the two sources.

653 Dr Mutimer's report [PEN.010.0310] at 0313

654 Day 1, page 75

655 Report [PEN.010.0310] at 0310 and 0313

656 Affidavits of Mrs Jean Tamburrini [PEN.018.1544], Charlie Cunningham [PEN.018.1549], Stephen Clocherty [PEN.018.1547] and Bernard Fisher [PEN.018.1559]

657 Affidavit of Mrs Jean Tamburrini [PEN.018.1544]

658 Affidavit of Charlie Cunningham [PEN.018.1549]

659 Affidavit of Stephen Clocherty [PEN.018.1547]

660 Affidavit of Bernard Fisher [PEN.018.1559]

661 Statement of Mrs Jean Tamburrini [PEN.001.0309]

662 Affidavit of Bernard Fisher [PEN.018.1559]

663 Dr Mutimer's report [PEN.010.0310] at 0313

664 Letter from the GRI to the Glasgow Dental Hospital dated 8 August 2001 [TAM.001.2542]

665 Dr Mutimer's report [PEN.010.0310] at 0311

666 Dr Mutimer - Day 1, pages 94-95

667 Dr Mutimer's report [PEN.010.0310] at 0311

668 Report of ultrasound scan [TAM.001.2699]

669 Letter from the GRI to GP dated 9 December 2001 [TAM.001.2557] at 2558

670 Hepatoma is primary hepatocellular carcinoma.

671 Report of MRI scan [TAM.001.2697]

672 Letter from the GRI to GP dated 13 December 2001 [TAM.001.2564]; Dr Mutimer - Day 1, page 106; Dr Bathgate - Day 1, page 31

673 Letter from the GRI to GP dated 13 December 2001 [TAM.001.2564]

674 Letter from the GRI to GP dated 20 December 2001 [TAM.001.2563]

675 Letter from the GRI to GP dated 15 January 2002 [TAM.001.2562]

676 Letter from the GRI to GP dated 25 January 2002 [TAM.001.2561]

677 Day 1, page 106

678 Report of scan [TAM.001.2695]

679 Letter dated 15 February 2002 [TAM.001.2566]

680 Letter from the GRI to RIE LTU [TAM.001.2565]

681 Dr Mutimer's report [PEN.010.0310] at 0311; Dr Bathgate - Day 1, page 31

682 Computerised tomography scan, sometimes also known as CAT scan.

683 Letter from the GRI to RIE LTU dated 14 February 2002 [TAM.001.2565]; Dr Bathgate - Day 1, pages 31-33

684 Witness Statement of Mrs Jean Tamburrini [PEN.001.0309] at 0312

685 Letter from LTU RIE to GP dated 5 March 2002 [TAM.001.2524]

686 Ibid [TAM.001.2524] at 2525

687 Day 1, page 35

688 Letter from LTU RIE to GP dated 5 March 2002 [TAM.001.2524] at 2525

689 Letter from LTU RIE to GP dated 9 April 2002 [TAM.001.0900]

690 Ibid [TAM.001.0900]; Dr Bathgate - Day 1, page 35

691 Letter from RIE LTU to GP dated 26 August 2002 [TAM.001.0881]

692 Ibid [TAM.001.0881] at 0883

693 Witness Statement of Mrs Jean Tamburrini [PEN.001.0309] at 0312

694 Letter from the GRI to the RIE LTU dated 3 July 2002 [TAM.001.2533]

695 Letter from the RIE LTU to GP dated 24 July 2002 [TAM.001.2470]

696 Dr Bathgate - Day 1, pages 40-41

697 Letter from the RIE LTU to GP dated 26 August 2002 [TAM.001.0881]

698 Disorder of the brain, a late complication of cirrhosis.

699 Letter from the RIE LTU to GP dated 16 October 2002 [TAM.001.0878]

700 Witness Statement of Mrs Jean Tamburrini [PEN.001.0309] at 0312

701 Letter from the RIE LTU to GP dated 13 December 2002 [TAM.001.0876]

702 Ibid [TAM.001.0874]

703 Ibid [TAM.001.0874]

704 Letter from the RIE LTU to GP dated 13 December 2002 [TAM.001.0872]

705 Endoscopic retrograde Cholangiopancreatography.

706 Letter from the RIE LTU to GP dated 14 December 2001 [TAM.001.0869]

707 Day 1, pages 107-108

708 Letter from the RIE LTU to GP dated 31 December 2002 [TAM.001.0867]

709 Letter from the RIE LTU to GP dated 21 January 2003 [TAM.001.0862]

710 Letter from the RIE LTU to GP dated 4 February 2003 [TAM.001.0859]

711 Ibid [TAM.001.0859]; Witness Statement of Mrs Tamburrini [PEN.001.0309] at 0313

712 Letter from the RIE LTU to GP dated 17 March 2003 [TAM.001.0857]; Dr Mutimer's report [PEN.010.0310] at 0312

713 Letter from the RIE LTU to GP dated 17 March 2003 [TAM.001.0857]

714 Letter from the RIE LTU to GP dated 16 April 2003 [TAM.001.0842]; Letter from the RIE LTU to GP dated 25 June 2003 [TAM.001.0835]

715 Letter from the RIE LTU to GP dated 4 August 2003 [TAM.001.0832]

716 Ibid [TAM.001.0832]

717 Witness Statement [PEN.001.0309] at 0313

718 Letter from the RIE LTU to GP dated 11 September 2003 [TAM.001.0830]

719 Witness statement of Mrs Tamburrini [PEN.001.0309] at 0313

720 Letter from the RIE LTU to GP dated 13 November 2003 [TAM.001.0824] at 0825: the problem so noted was not restricted to obstruction. It indicated that the liver was working very badly and could properly have been described as 'cholestatic'.

721 Letter from the RIE LTU to GP dated 8 December 2003 [TAM.001.0814] at 0815

722 Specifically Genotype 1A. But the distinction between 1A and 1B is not relevant for present purposes. See Chapter 13, Knowledge of Viral Hepatitis Now, paragraph 13.14 for discussion of HCV genotypes.

723 Dr Bathgate's report [TAM.001.2380] at 2382 and 2384; Day 1, page 56

724 Letter from the RIE LTU to GP dated 15 December 2003 [TAM.001.0812]

725 Day 1, page 56

726 Letter from the RIE LTU to GP dated 15 December 2003 [TAM.001.0812]

727 Witness Statement of Mrs Jean Tamburrini [PEN.001.0309] at 0314

728 Letter from the RIE LTU to GP dated 3 March 2004 [TAM.001.0799]

729 Witness Statement of Mrs Jean Tamburrini [PEN.001.0309] at 0314; Letter from the RIE LTU to the GRI dated 11 February 2004 [TAM.001.0804]. Letter from the RIE LTU to GP dated 3 March 2004 [TAM.001.0799]

730 Dr Mutimer's report [PEN.010.0310] at 0312

731 Day 1, pages 108-109

732 Dr Mutimer's Report [PEN.010.0310] at 0312

733 Letter from the RIE LTU to GP dated 3 March 2004 [TAM.001.0799]

734 Letter from the RIE LTU to GP dated 1 April 2004 [TAM.001.0795]; Dr Bathgate - Day 1, page 61

735 Dr Mutimer's report [PEN.010.0310] at 0312

736 Letter from the RIE LTU to GP dated 1 April 2004 [TAM.001.0795]

737 Ibid [TAM.001.0793]; Dr Bathgate - Day 1, pages 64-65

738 Letter from the RIE LTU to GP dated 28 April 2004 [TAM.001.0789]

739 Dr Bathgate - Day 1, pages 65-66

740 Dr Mutimer's report [PEN.010.0310] at 0313

741 Ibid

742 Letter from the RIE LTU to GP dated 28 June 2004 [TAM.001.0781]

743 Ibid [TAM.001.0781]

744 Dr Mutimer's Report [PEN.010.0310] at 0313

745 Letter from the RIE LTU to GP dated 22 July 2004 [TAM.001.0774]; Letter from the RIE LTU to GP dated 14 September 2004 [TAM.001.0768]

746 Letter from the RIE LTU to GP dated 20 September 2004 [TAM.001.0762]; Dr Bathgate - Day 1, page 69

747 Letter from the RIE LTU to GP dated 22 November 2004 [TAM.001.0740]; Dr Bathgate - Day 1, pages 70-72

748 Dr Mutimer's Report [PEN.010.0310] at 0314

749 Ibid [PEN.010.0310] at 0313-0314; Dr Mutimer - Day 1, page 115

750 Ibid at 0314-0315; Dr Mutimer confirmed in evidence (Day 1, page 116) that the date of June 2003 given on page 0314 of his report should be June 2004.

751 Death certificate [TAM.001.2946]

752 Day 1, pages 71-72

753 Dr Bathgate's report [TAM.001.2380] at 2387; Day 1, page 72

754 Day 1, page 115; Dr Mutimer's report [PEN.010.0310] at 0313-0314

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