Final Report

< Back to final report index page

Chapter 16

Knowledge of Viral Hepatitis 3 - 1986 Onwards


16.1 This chapter continues the account of the development of knowledge of non-A, non-B Hepatitis (NANB Hepatitis) from 1986 through to the discovery of the Hepatitis C virus (HCV) and beyond. Some of the later developments described are also reflected in Chapter 13, Knowledge of Viral Hepatitis Now. They are repeated here for the context in which they arose and particularly to provide chronological references for developments in screening blood and testing blood donors, further developments in the treatment of blood components and products and other topics dealt with separately.

16.2 As noted in the previous chapter (paragraphs 15.108-15.110), in 1986 expert opinion in the USA was moving towards general support for surrogate testing as a means of excluding from the donor pool as many donors infected with NANB Hepatitis virus(es) as possible.[1] That development resulted in the general introduction of surrogate screening of blood for alanine transminase (ALT),[2] and testing of donors for antibodies to the Hepatitis B virus. That course was not to be followed in the UK however, although in other respects opinion in the UK began to change in the same period. Correspondence in The Lancet in February 1986 marked the beginning of a change in attitudes towards NANB Hepatitis.

Changing attitudes towards non-A, non-B Hepatitis

Correspondence in The Lancet

16.3 A letter by Klaus Schimpf (Heidelberg, West Germany) published on 8 February 1986,[3] expressed agreement with the report in 1985 by Dr Charles Hay and his colleagues in Sheffield[4] that progressive liver disease in haemophilia patients was an understated problem. In Schimpf's study 52 biopsies were carried out on 45 patients between 1972 and 1985. There were signs of subsided hepatitis in 24% of the patients, of chronic persistent hepatitis in 27% and of progressive liver disease in 29% (16% chronic active hepatitis, 13% cirrhosis). Schimpf also noted that the multi-centre study by Louis Aledort and others had come to a similar conclusion regarding the frequency of cirrhosis.[5]

16.4 The same edition of The Lancet contained an update on the condition of 12 patients who had developed NANB Hepatitis after treatment with a new intravenous gammaglobulin preparation produced by the Blood Products Laboratory, Elstree (BPL, the manufacturer of NHS blood products in England).[6] At least half of the patients had evidence of progressive liver disease, with cirrhotic changes in three. While specific to patients with primary hypogammaglobulinaemia (an immune deficiency characterised by a reduction in gamma globulins and treated with blood products), the letter emphasised that NANB Hepatitis was a serious complication that should be controlled by discarding plasma donations with raised ALT levels.

16.5 An editorial in The Lancet of 2 August 1986 stated:

The risk of contracting [NANB Hepatitis] from factor VIII and IX concentrates was first recognised ten years ago. The requirement for large pools of plasma, of up to 7000 donations in the UK ... and even larger pools with some commercial preparations, has produced attack rates approaching 100% in recipients after first exposure to unheated factor VIII. The acute illness was often mild .... Unfortunately, it is now clear that there is a substantial long-term risk of chronic sequelae, such as chronic active hepatitis and cirrhosis of the liver. Reports of serial liver biopsies in patients regularly treated with factor VIII and IX suggest that the risk of serious chronic liver disease may be as high as 16%.


Despite intensive research, the virus or viruses associated with non-A, non-B (NANB) hepatitis have not been isolated or characterised.[7]

16.6 By the end of 1986, informed opinion in the USA (as typified by Alter and colleagues) and in parts of Europe had shifted decisively to reflect suspicion that the long-term progression of chronic NANB Hepatitis infection was not benign but severe, whether following blood transfusion or in haemophilia patients.

Increasing concern

16.7 In 1987, the 8th edition of the standard UK textbook on blood transfusion was published.[8] Post-transfusion NANB Hepatitis was said to be present when, between two and 26 weeks after transfusion, two consecutive blood samples showed a twofold increase in ALT levels - effectively the approach to diagnosis adopted in the USA. That method of diagnosis was described by Patrick Mollison, the author of this authoritative text, as 'most unsatisfactory' and was said to have led to 'a great deal of uncertainty about the true incidence' of post-transfusion NANB Hepatitis. It was estimated that NANB agents had caused 20-42% of sporadic cases of hepatitis in the USA,[9] compared with 13% within the UK.[10] Mollison wrote:

[NANB post-transfusion hepatitis] is usually mild and asymptomatic during the acute phase .... However, prospective studies in the USA have shown that the chronic sequelae of [NANB post-transfusion hepatitis] may be serious. Over 50% of patients develop chronic hepatitis as judged by persisting or fluctuating rises in [ALT] levels lasting for at least 1 year after onset of the disease and in most for more than 3 years .... Although the chronic phase of [NANB post-transfusion hepatitis], like the acute phase, tends to be mild,[11] some patients develop severe chronic liver disease and 10% of these patients progress to cirrhosis which is generally milder than alcoholic cirrhosis.[12]

16.8 It was noted that the available data were based on biopsies in very small numbers of patients.[13]

16.9 In a letter to the British Medical Journal (BMJ) published on 14 February 1987, Dr John Gillon and Dr Brian McClelland (both of the Edinburgh and South East Scotland Blood Transfusion Service) commented that only one study of the long-term consequences of post-transfusion NANB Hepatitis infection had been reported.[14] This was a reference to the Alter study.[15] The letter narrated that of the 50% of cases which became chronic as evidenced by raised ALT levels persisting for more than six months, 10-15% might be expected to show evidence of clinically important liver disease. As noted in the Preliminary Report,[16] applied to the UK these figures were almost certainly an overestimate. However, it is of greater importance that at this time the authors did not have locally relevant data to draw on. There was still considerable uncertainty but some growing understanding. At an international symposium on viral hepatitis and liver disease held in London in May 1987, Dr Alter said:

NANB remains a frustrating and perplexing dilemma. Nonetheless we know a little more about its physical properties, we know considerably more about its clinical outcome, and we know of multiple ways in which it can be inactivated. What we do not know exactly is where to go next, or what can be done to create the breakthrough that will allow progress with NANBH to parallel that with hepatitis B and hepatitis A.[17]

16.10 There were other international meetings at the time, reflecting increasing concern. As noted in the Preliminary Report, the European Health Committee of the Council of Europe held its 21st meeting between 29 June and 1 July 1987.[18] The prevailing uncertainty was reflected in the extract of a report of the 10th meeting of the Committee of Experts on Blood Transfusion and Immunohaematology circulated for that meeting.[19]

Scientific developments: discovery of the Hepatitis C virus

16.11 The scientific background was about to change. On 10 May 1988, the Chiron Corporation announced that:

Scientists at Chiron Corporation have identified, cloned and expressed proteins from a long-sought blood-borne hepatitis non-A, non-B virus, and have developed a prototype immunoassay that may lead to a screening test for hepatitis non-A, non-B antibodies ....[20]

16.12 Scientific details were not published at that time,[21] although the report of the Chiron discovery in Nature said: 'The search for the elusive viral agent responsible for [NANB] hepatitis may be over.'[22] Throughout the remainder of 1988 there was little in the way of published material on HCV and no technical support for the claim. In the UK public sector, research was focused on virus inactivation. There was powerful support for that approach. In an article published in The Lancet in December 1988, Dr Alter and others stated:

Because [of] the increasing number of direct and indirect donor screening measures required to protect the blood supply, the most promising approach to the reduction of transfusion-associated disease is the biophysical removal or biochemical inactivation of hepatitis and other blood transmitted viruses ....[23]

16.13 Work in that area is discussed in Chapters 23 and 24.

16.14 In the short term, the Chiron report was scarcely noted in published statements by commentators who remained pre-occupied with the natural history of the disease. Although there was growing appreciation that there were risks associated with the use of plasma products, the prevailing view among Scottish Home and Health Department (SHHD) medical staff remained that NANB Hepatitis was generally benign - a view that would have received support from the 7th edition of Professor Sherlock's book (discussed in the last chapter at paragraph 15.168). In Scotland, there had been a report of four cases of infection that might have been transmitted by intravenous immunoglobulin manufactured at the Protein Fractionation Centre (PFC, the manufacturer of NHS blood products in Scotland), Edinburgh, during 1987.[24] In an internal memorandum to Mr Hamish Hamill at the SHHD dated 30 August 1988, Dr John Forrester noted that the product was under suspicion of transmitting NANB Hepatitis, but concluded:

[T]his particular hepatitis is so benign, at least in the short term, that evidence of transmission has to be specially sought, the patient not being ill at all in the ordinary sense.[25]

Progressive disease as an aspect of the natural history of non-A, non-B Hepatitis

16.15 There were still differences of view among medical practitioners generally about the seriousness of NANB Hepatitis infection. An editorial in The Lancet in December 1988 summarised the recent history of 'Chronic liver disease and haemophilia'.[26] The editorial noted that while acute post-transfusion hepatitis and chronic increases in liver enzyme concentrations had long been associated with both Factor VIII and Factor IX infusion, those caring for haemophilia patients were slow to accept chronic progressive liver disease as an important complication. It was noted that few haemophilia patients had any signs or symptoms of liver disease, deaths from hepatic failure were rarely reported and raised ALT levels were attributed to chronic persistent hepatitis rather than chronic active hepatitis. The results from studies of early series of patients undergoing liver biopsy were generally reassuring in that most of them showed either chronic persistent hepatitis or mild chronic active hepatitis, with little to suggest severe liver damage.[27] However, as noted in paragraph 16.3 above, Hay and colleagues (1985) had documented a significant progression from chronic persistent hepatitis to chronic active hepatitis to cirrhosis.[28] Their assessment was echoed by Schimpf (paragraph 16.3, above).[29]

16.16 Similar figures were provided in a contemporaneous report from Dr Elizabeth Miller and colleagues in London (1988).[30] The editorial stated:

The evidence that chronic progressive liver disease is an important complication of haemophilia treatment is therefore becoming increasingly persuasive. Furthermore, experience with other types of viral hepatitis suggests that cirrhosis and hepatocellular carcinoma may first appear decades after infection.[31]

16.17 Opinion was moving towards acceptance of more progressive disease as an aspect of the natural history of NANB Hepatitis.

Reactions to the Chiron announcement and further scientific developments

16.18 There were mixed responses to the initial announcements of Chiron's discoveries. The American Association of Blood Banks (AABB) reported that, while there remained some scepticism about the results, a leading expert in the field, Harvey Alter (US National Institutes of Health) had said that Chiron's identification of the NANB Hepatitis protein was 'what we've been looking for for 10 years... one has to be skeptical but the data I've seen looks very good'.[32] The AABB commented:

Because Chiron has not yet published its results some scepticism remains about their findings....

Health experts agree that further testing still needs to be performed because the protein identified may be one of several capable of causing non-A, non-B hepatitis.[33]

16.19 At the end of 1988 publication of scientific analysis of Chiron's work was still awaited.

16.20 Dr Brian Dow, at the time a Senior Grade Scientific Officer at the West of Scotland Blood Transfusion Service, gave evidence that he thought he had been aware of Chiron's discovery at this time but had been unwilling to believe it was true until the first generation tests were available.[34] It appears that this was a common attitude.

16.21 Details of Chiron's discovery and resulting test were not published until the following year when, on 21 April 1989, Qui-Lim Choo and others published scientific details of the isolation of the genome of HCV.[35] At the same time, George Kuo and others (Chiron, US National Institutes of Health and others) published details of an assay to detect antibodies to HCV.[36] The test had been developed by Ortho Diagnostics Systems (Ortho) in conjunction with Chiron.

The science of discovery

16.22 Chiron had inoculated a chimpanzee with a serum sample[37] from a patient with post-transfusion hepatitis and had cloned the putative virus. Serum was taken from another patient who had recovered from post-transfusion NANB Hepatitis and was assumed to have produced antibodies to the NANB agent. The antibodies were 'labelled' and introduced to the putative virus. An appropriate reaction was observed which showed the connection required to verify the hypothesis that the cloned material was, or included, the agent of transmission of NANB Hepatitis.[38]

16.23 It is appropriate to set out the story a little more fully to indicate why the discovery had such an impact on understanding of the infection. At the outset of the process, the subject, a patient who was known to have had a transfusion, was believed to have become ill with NANB Hepatitis about three weeks after the procedure. To test that hypothesis, serum from the patient was injected into a chimpanzee called Rodney. Rodney developed hepatitis, an essential step in removing any doubt whether the episode in the patient was due to an infectious agent, since it demonstrated transmissibility.[39]

16.24 A sample of serum was taken from Rodney and RNA and DNA were extracted. At that stage it was not known whether the postulated transmissible agent was an RNA or DNA virus.[40] Reverse transcriptase, an enzyme that allows RNA to convert into DNA, was added to the genetic material extracted from Rodney's serum, with the result that the whole genetic material present was DNA. The DNA would include chimpanzee DNA but it would also include the DNA of the putative virus if it were present. That material was then put into plasmids, a vehicle that enabled the expression (synthesis) of the DNA code of whatever proteins had been introduced, in the case of a virus in the same way as the virus would normally synthesise proteins.[41] The product of that exercise was then put into E-coli for propagation in the hope that, as the bacteria reproduced, the introduced DNA from the chimpanzee and the putative virus would also reproduce genetically in the bacterial cells. This was the only way in which the viral DNA would encode for the protein which was part of the structure of the putative virus.[42]

16.25 At that stage, serum was taken from a patient who was known to have had post-transfusion NANB Hepatitis and who was assumed to have developed antibodies to the virus. Using an appropriate ligand, a radioisotope or an enzyme label that creates a coloured substrate, the antibodies were labelled as human virus antibodies. When introduced to the material propagated in E. coli, the labelled antibodies were expected to differentiate and bind to any human virus protein or DNA present and not to chimpanzee DNA. Such a reaction would be identified radioactively or by chemi-luminescence.[43] The reaction was observed in a tiny minority of the wells into which the samples were dispensed but showed the necessary connection.

16.26 Chiron's overall procedures and approach to finding the virus and its procedures were not fundamentally unique: many researchers had tried similar approaches, but without success. There may have been many reasons for failure, including the use of virus material that did not include an antigenic component common to all the genotypes of the virus.[44] However, so much effort had been expended in searching for the putative virus in so many centres worldwide that by 1987-88 many people had given up believing that there was a virus, preferring the explanation that a chemical reaction caused the transaminase rise in patients in much the same way as some drugs used in medication can cause hepatitis.[45] Chiron's advantages were having 'well-pedigreed' chimpanzee sera to establish the transmission of hepatitis through passage (the sequential process from the initial patient through two chimpanzees in succession which proves the existence of a transmissible agent); and sera containing a large amount of virus. The infective serum from the first chimpanzee was diluted until it no longer transmitted hepatitis,[46] enabling Chiron to calculate the amount of virus in the initial sample.[47] For this work Chiron was granted a patent and lengthy and complex litigation followed. So far as is material, the challenge to the patent failed.[48]

16.27 The publication of details of the Chiron discoveries marked the beginning of a period of research, both into the characteristics of HCV and into the effectiveness of markers of HCV infection and corresponding developments in treatment. The term 'Hepatitis C' almost entirely supplanted 'NANB Hepatitis' in the discussion of liver disease following Chiron's breakthrough in the understanding of NANB Hepatitis. The terms have never, however, been truly synonymous.

16.28 The articles by Choo and others and Kuo and others referred to above were highly technical. The identification of the virus depended on the characterisation of the clones produced. The conclusions, and claims, were significant:

Thus, our data indicate that clones 5-1-1 and 81 are derived from the genome of a blood-borne NANBH virus that we now term the hepatitis C virus (HCV) ... Our present data showing that the virus contains a positive-stranded RNA molecule of at least 10,000 nucleotides is consistent with it being related to the togaviridae or flaviviridae ....The cDNA clones reported here were obtained in the absence of prior knowledge concerning the virus, the viral genome, and the presence of circulating viral antibodies. As such, this represents cloning without prior characterization of the infectious agent.[49]

16.29 In retrospect, the Chiron discovery was to prove more significant than was appreciated at the end of the 1980s and into the early 1990s. Other topics continued to attract attention. The scientific basis for the work was not readily understood and general understanding only developed over time. The background to Chiron's work set out above helps to explain the difficulties. Professor Thomas encapsulated the discovery in a brief, and somewhat concentrated, statement:

[Chiron] reported the cloning of HCV in 1989, by antibody probing of an expression library made from a reverse transcribed RNA extract of the serum of an infected chimpanzee initially inoculated with a serum sample from a patient with post-transfusion hepatitis (PTH). The antibody source was a serum specimen from a subject who had recovered from post-transfusion NANB hepatitis and was assumed to have produced antibodies to NANB agent.[50]

16.30 The concepts, and the language, reflect a highly sophisticated knowledge of the biology of virus replication. The current understanding of the position has been set out in Chapter 13, Knowledge of Viral Hepatitis Now. However, this would have been science understood by only a few at the end of the 1980s.

16.31 Chiron had achieved a significant, and inventive, development in knowledge of HCV infection but the work was incomplete: the whole virus had not been identified. In Chiron's experiments, the antigen recognised by the antibody in the recovered patient's serum was in the region NS4, one of the enzymes known as proteases that came, in time, to be targeted by protease inhibitors which increase substantially patients' response rates to treatment by impairing the ability of the virus to reproduce. Not all genotypes of HCV[51] have NS4 proteins, however, and this was to affect the usefulness of early forms of the assay developed. Without a sophisticated knowledge of cell biology, incomplete research findings were almost bound to leave even the most interested and careful commentators with reservations about the discovery.

16.32 In the context of transfusion-related transmission and blood product therapy, post-transfusion Hepatitis C now appears to explain most if not all cases of what was NANB Hepatitis viral infection. Before the discovery of HCV, however, many people infected with the virus would not have been labelled as 'non-A, non-B' patients: there were few NANB Hepatitis diagnoses.[52] Alcohol and alcoholic liver disease were often associated with hepatitis and many patients were labelled as having 'alcoholic liver disease' alone, where two (or possibly more) risk factors would now be recognised, giving rise to much of the stigma associated with infection.[53]

Unresolved issues in non-A, non-B Hepatitis

16.33 The balanced view of the state of knowledge in 1989, as reflected in the eighth edition of Sherlock's Diseases of the Liver and Biliary System, published that year but continuing to reflect to a considerable extent views expressed in earlier editions, was that NANB Hepatitis was still 'ill defined'.[54] As regards the parenteral type of NANB Hepatitis, Professor Sherlock stated:

The causative agent has not hitherto been identified ... [although] a viral genomic clone has been isolated from infected plasma and liver. This encodes the antigen associated with non-A, non-B viral hepatitis in man and chimpanzees.[55]

16.34 It is likely that the text was written before publication of the more definitive Chiron papers in 1989 and Professor Sherlock's comment reflects information provided in the original Science announcement. Chiron's discoveries were not presented in her text as resolving the aetiology of NANB Hepatitis.

16.35 On the other hand, Professor Sherlock's analysis of the clinical manifestations of infection with NANB Hepatitis presented a more serious and accurate picture than before. It was now thought that 60% of patients would have raised serum transaminases one year after infection. In 68% the disease became chronic and cirrhosis developed in 20%.[56] She stated that prognosis was very variable. In some cases, the diseases were benign with spontaneous biochemical improvement over one to three years. In others, chronic persistent hepatitis and chronic active hepatitis could convert to more serious disease and even go on to cirrhosis. In general, however, despite biochemical evidence of disease, the patient was asymptomatic and the development of hepatic failure was rare. Hepatocellular cancer had been recorded but was exceedingly rare.[57] In contrast to the seventh edition, a relationship to hepatocellular cancer was now acknowledged.

16.36 Another insight into the perception of NANB Hepatitis among virologists in the UK at the end of 1988 was provided in a paper entitled 'Unresolved issues in non-A, non-B hepatitis' delivered by Professor Arie Zuckerman (Professor of Microbiology, Royal Free Hospital School of Medicine, London), presented at the Second International Symposium on Viral Hepatitis and Hepatocellular Carcinoma in Taipei in December 1988.[58]

16.37 Professor Zuckerman stated that NANB Hepatitis was the most common form of hepatitis occurring after blood transfusion in some parts of the world (possibly 90% where blood donations were screened for HBsAg by sensitive tests) and that there was evidence of at least two transmissible agents.[59] It occurred in haemodialysis and other units and could be transmitted by therapeutic plasma components. He noted that there was preliminary information of an association with hepatocellular carcinoma, and commented generally on NANB Hepatitis:

Although in general the illness is mild and often subclinical or anicteric, severe hepatitis with jaundice does occur and the infection is a significant cause of fulminant [rapidly progressing] hepatitis. There is considerable evidence that the infection may be followed in many patients ... by prolonged viraemia and the development of a persistent carrier state. Studies of histopathological sequelae of acute non-A, non-B hepatitis infection revealed that chronic liver damage, which may be severe, may occur in as many as 40 - 50% of the patients.[60]

16.38 Professor Zuckerman said that clinical evidence of more than one type of the disease was based on observation of multiple attacks of hepatitis in individual patients and experimental laboratory research. He dismissed argument based on incubation periods. His own explanation of the occurrence of multiple attacks was subsequently shown to be wrong. It later transpired that multiple attacks of Hepatitis C could occur because of insufficient host immunity to different genotypes of HCV rather than because of the existence of more than one viral species. However, that knowledge depended on advanced genetic research that still lay in the future. Like Professor Sherlock in the eighth edition of her book, Professor Zuckerman was writing before publication of the scientific data supporting Chiron's claims. It appears that neither Professor Sherlock nor Professor Zuckerman was willing at that stage to arrive at final conclusions on what was known of Chiron's discoveries.

16.39 It is apparent that, despite the novelty of Chiron's science, or perhaps because of it, there was not immediate and universal acceptance of its validity. The initiative, in terms of fundamental research into HCV, continued to lie with Chiron and the US Centers for Disease Control.

16.40 The second meeting of the Advisory Committee on the Virological Safety of Blood (ACVSB) took place on 22 May 1989.[61] Professor Zuckerman's Taipei paper was circulated along with a second paper, from an unidentified but clearly official source,[62] and members were given the results of the Council of Europe questionnaire prepared by Dr Gunson and the report of the Committee of Experts on Blood Transfusion and Immunohaematology from May 1987. In addition, scientific data from Chiron was available. The article published by Choo and others in Science was referred to and the accompanying paper noted:

The data suggests that NANB hepatitis agent is similar to the togaviridae or flaviviridae. The authors refer to this virus as hepatitis C virus.[63]

16.41 The discussion of NANB Hepatitis was brief, so far as reported in the minute of the meeting. It was recorded that members had advised that, although colleagues in the USA considered that only one virus caused NANB Hepatitis, there might be two or more. The question whether there was more than one agent of transmission continued to arise. An editorial in The Lancet on 5 August 1989, 'Will the real hepatitis C stand up?', discussed the question whether there was a distinct short incubation agent with reference to reports of observations of apparently different incubation periods.[64]

16.42 However, in general, interest came increasingly to focus on the Chiron/Ortho test. It was in that context that political interest was aroused by articles in The Guardian[65] and The Scotsman[66] in August 1989 that were likely to cause public concern. The article in The Guardian, for example, stated that '6000 people last year may have received blood transfusions contaminated with hepatitis C'. There was official reaction to the media comment.

16.43 On 23 August Mr George Tucker (SHHD) sent a memorandum to Mr Michael Forsyth, MP, then Under-Secretary of State in the Scottish Office with responsibility for health: 'Testing of blood donations - test for Hepatitis C'.[67] Mr Tucker dealt with the claim in The Guardian: the statement was said to be 'unnecessarily alarmist', as it assumed that one per cent of all donations came from donors who were infectious (and not simply carriers) and that they passed on the antigen, and not just the antibody, in their donation. It also said that only a minority of those infected with Hepatitis C displayed any symptoms either in the short or long term. The memorandum further noted that the prevalence of HCV in the population had not been established and nor had the role of blood in its transmission. The UK Health Departments, along with the UK blood transfusion services, were said to be examining all the available data. The main focus of the memorandum was the position of the SHHD and the DHSS on testing, and that may explain the brevity of the information provided on the prevalence and consequences of infection.

16.44 From the position adopted by Professor Zuckerman at the end of 1988 through to September 1989, expert opinion was consistent in the UK and more widely. Dr Ruthven Mitchell (SNBTS, Glasgow) attended and produced a report of proceedings at an international meeting on HCV, organised by Ortho and held in Rome on 14-15 September 1989.[68] There had been discussion at the conference on the prevalence and sequelae of NANB Hepatitis. Dr Mitchell's report stated that about 10% of persons transfused developed NANB Hepatitis, which could be of two forms, an acute form and a chronic form.[69] The incubation time varied from a few weeks to months. About 90% of post-transfusion hepatitis was due to the NANB Hepatitis virus or viruses. About 50% of those would become chronic and, of those, 20% would develop cirrhosis or some long-term liver impairment. Prevalence of the Hepatitis C antibody (anti-HCV) varied among different countries. Patients in the highest risk categories had the highest prevalence of anti-HCV. People with haemophilia had an anti-HCV prevalence of 60-80%.

16.45 Dr Gunson reported the proceedings of the Rome meeting to the meeting of the Advisory Committee on Transmission Transmitted Diseases (ACTTD)[70] on 9 October 1989. His report included a recommendation in the following terms:

The Committee is asked to approve the routine testing of blood donations for anti-HCV in principle and request the National Directors in England and Scotland to arrange for the simultaneous introduction of the tests at an appropriate time when a policy for handling the seropositive donors has been defined.[71]

16.46 It would be almost two years before the simultaneous introduction of testing of blood donations for anti-HCV was introduced throughout the UK. This delay is discussed in Chapter 31, The Introduction of Screening of Donated Blood for Hepatitis C.

16.47 After this time, there was a change in the proportions of individuals reported to be affected by adverse sequelae of infection. On 8 January 1991 at the sixth meeting of the ACTTD, a paper prepared by Dr Gillon (SNBTS, Edinburgh) on counselling of donors was also discussed.[72] Dr Gillon was a member of the SNBTS Working Party on Donor Counselling for HCV, along with Drs R Crawford, G Galea and J Davidson. The fourth draft of their report[73] found that there were thought to be at least two NANB Hepatitis viruses, but that Hepatitis C was almost certainly the most common form, thought to be responsible for around 70% of post-transfusion hepatitis. This misapprehension occurred because first generation antibody tests detected only part of the variable 'non-structural' part of the virus - NS4 - which was only present, in this form, in about 70% of HCV cases overall (see paragraph 16.31 above). Once subsequent antibody tests to less variable parts of the virus had been developed, it was realised and accepted that almost all post-transfusion NANB Hepatitis could be ascribed to HCV. The report stated that most people with NANB Hepatitis would be asymptomatic but that some would go on to develop long-term liver damage: around 10-15% of those with post-transfusion NANB Hepatitis might eventually develop significant liver disease. The prevalence of carriage of NANB Hepatitis in the general donor population was not known. The prevalence of confirmed anti-HCV in UK donors was likely to be around 1 in 1000 (0.1%). Preliminary studies on Scottish blood donors showed that approximately 0.5% were repeatedly positive.

16.48 By this stage, however, expert opinion was moving towards adopting HCV screening and the numerical data on prevalence came to be discussed in that context. Effective HCV testing of blood donors was introduced on 1 September 1991 and formed a new setting for study of the infection. Material became available to assess the prevalence of disease and prospective studies of the progress of infection became more practicable. The introduction of testing did not, however, resolve the question of the historic prevalence of infection nor of the numbers of patients likely to survive with the infection.

16.49 In the 1990s, many countries initiated 'look-back' studies to identify patients who had received infected blood,[74] in an attempt to assess the prevalence of HCV infection in their populations. Work in south east Scotland found that look-back for Scottish patients would be feasible and practicable. After review on 11 January 1995, UK Ministers announced a national look-back following the East of Scotland Blood Transfusion Service model.[75] This topic is discussed in Chapter 35, An Investigation into the Steps Taken to Identify the Individuals who were Infected (Look-back).

16.50 The UK national HCV look-back exercise carried out between 1995 and 1998 resulted in the creation of the National Hepatitis C Register as a research tool at the Health Protection Agency (HPA), Colindale, in 1998. The initial UK exercise was closed to new entrants in 1998.

16.51 Anonymised data from all patients identified by the look-back exercise as having contracted Hepatitis C as a result of transfusion were entered into the central register at the HPAs Centre for Infections. Systematic collection of clinical data using standardised report forms allowed data to be gathered in a uniform way approximately every two years. The data, along with mortality data for patients on the register and for controls, allowed the clinical course of HCV infection to be established and risk factors for progressive disease to be investigated.

16.52 The Scottish exercise continued formally until 1998. On 10 June that year Dr Aileen Keel, Senior Medical Officer, SHHD, wrote to Professor Ian Franklin, Medical and Scientific Director, SNBTS.[76] Dr Keel informed Professor Franklin that the Advisory Committee on the Microbiological Safety of Blood and Tissue for Transplantation had resolved that all reasonable measures had been taken to trace components and recipients in Scotland and that the tracing exercise could stop.

16.53 As the look-back exercises were coming to an end, constitutional change was implemented, with the Scottish Executive (now the Scottish Government) and Scottish Parliament convened on 1 July 1999. Description of the next stages in the developing knowledge of HCV needs to take account of the changes brought about by devolution. The differing courses of action followed in England, Wales and Scotland were described in the report of a meeting of the All-Party Parliamentary Hepatology Group on 18 November 2008.[77] Professor David Goldberg, Chair of the Action Plan Governance Board, gave evidence on the Hepatitis C Action Plan of the Scottish Government.[78] Phase I of the Plan comprised evidence gathering, which disclosed that an estimated 38,000 people were living with the virus in Scotland, of whom 14,800 had been diagnosed and only 2000 had ever received antiviral treatment. Cases of liver failure were increasing. HCV-related mortality had overtaken HIV mortality in the mid-1990s. Part II of the Plan detailed actions aimed at prevention of infection, diagnosis and treatment and care.

16.54 The prevalence of HCV infection in the blood donating population in both England and Scotland in the first six to 12 months after the introduction of screening was low, particularly in the case of repeat donors, among whom patients with higher risk factors had already been excluded by other means. Effective heat treatment of PFC coagulation products, which was achieved by the PFC in October 1985 for Haemophilia B patients and in April 1987 for Haemophilia A therapy, made a major contribution to the protection of those patients.[79] However, it transpired that the majority of batches of clotting factor concentrates made from volunteer blood donations before effective heat treatment was introduced were indeed infected and the frequency of transmission was similar following use of English and Scottish NHS and commercial material, as had already been inferred.[80] Screening of donations, from 1 September 1991, provided substantial protection for all recipients of blood, blood components and blood products.[81]

16.55 Most of the current knowledge of Hepatitis C (discussed in Chapter 13, Knowledge of Viral Hepatitis Now) developed after September 1991. With routine screening added to viral inactivation the threat of transmission of HCV infection by transfusion or by blood product therapy was substantially removed. Since then, new cases have been largely confined to needle sharing, mother to child transmission and medical procedures.[82] Practical implementation of Phase II of the Scottish Action Plan has been discussed in relation to the management of prisoners by the Western General Hospital, Edinburgh.[83] However, Professor Goldberg's view remains generally pessimistic:

Maintaining the current level of response is not an option if we are to interrupt the UK's relentless escalation in serious disease and death caused by hepatitis C. Action Plans without muscle have suboptimal impact. There is no time to lose.[84]

Perception of the severity of NANB Hepatitis/Hepatitis C

16.56 Professor Goldberg's comment is a reflection of the contemporary view of HCV infection. In the late 1980s there was a material change in the general perception of the severity of the sequelae of NANB Hepatitis infection. The stages in developing thought have been noted but, in order fully to appreciate the extent of the change, it is appropriate to summarise the main points.

16.57 From about 1978 doctors had monitored haemophilia patients' ALT levels more or less as a matter of course, but in the UK liver enzyme abnormalities without clinical signs of infection were not thought to be indicative of hepatitis. Probably, during the period 1980-88, there developed a general recognition among haemophilia doctors of the existence of NANB Hepatitis but most would have perceived the disease to have a generally benign prognosis.

16.58 Histology obtained by conventional biopsy was thought by the middle and later 1980s to be the most reliable way of monitoring the severity of liver disease.[85] Earlier misconceptions, based on the histological changes observed in patients with Hepatitis B infection and which had contributed to the inference that NANB Hepatitis was a disease with a generally benign prognosis, were set aside. It came to be appreciated that it was wrong to suppose that chronic persistent and chronic active hepatitis would follow the same clinical course in Hepatitis C as it does in Hepatitis B.[86] In the mid-1980s views had begun to change towards recognising NANB Hepatitis as a more serious condition: chronic persistent hepatitis in haemophilia patients was not as benign as hitherto supposed.[87]

16.59 Professor Howard Thomas[88] said that this was when views were changing.[89] His evidence is accepted as a reflection of the state of knowledge among experts at the cutting edge of research and clinical practice; general knowledge would develop more slowly. Two relevant conclusions follow. In the first place, there was no generally accepted view prior to 1985 that NANB Hepatitis had more than the generally benign prognosis described by Professor Sherlock before the 8th edition of her book. Secondly, from publication of the 8th edition in 1989 it was generally understood that NANB Hepatitis infection could be associated with serious disease. The development of generally accepted opinion in the second half of the 1980s is likely to have been subject to individual clinicians' access to, and understanding of, the latest developments in the field. It will not have been uniform and it will be likely to have been patchy until 1989.

16.60 By 1989, Professor Sherlock and others (including Professor Thomas) were engaged in studies, based on biopsy findings, which demonstrated that patients with chronic NANB Hepatitis had disease that covered the whole spectrum of acute and chronic hepatitis, including cirrhosis.[90] Professor Sherlock's view, as expressed in the 8th edition of her textbook in 1989, was changing towards recognition that NANB Hepatitis was a disease with a variable prognosis, ranging from a benign condition with spontaneous biochemical improvement after a few years to a chronic disease associated with cirrhosis in a significant proportion of patients, and hepatic failure and hepatocellular cancer in rare cases.

16.61 It is a material fact that early forms of treatment with Interferon became available for clinical testing in about 1989, soon after the announcement of the Chiron discoveries.[91] Interferon A was first used in England in 1989 and in Scotland in 1990-91. It would be some years before the grant of a licence and approval for use in England and Wales and before equivalent regulatory approval was given in Scotland, in November 1994. However, with the identification of the virus and the arrival of the first forms of therapy (initially thought to be more effective than events were to prove) there was an incentive to further develop knowledge of the disease.

Developments since 1991

16.62 Since effective viral inactivation, the infusion of blood products has not been associated with the transmission of Hepatitis C to any material extent. Largely retrospective research demonstrated that until then the frequency of transmission of HCV by Factor VIII concentrates, as shown by raised ALT levels, was similar in both commercial materials and the products of the UK public service fractionators.[92] More generally, transfusion of blood and blood components has not been associated with transmission of Hepatitis C since 1991 when screening of donated blood for HCV became universal practice in the UK. These events superseded the debate which had persisted between 1970 and 1990, as to whether volunteer blood donations were safer than those derived from paid donors, in particular blood products imported from the USA.

16.63 Current known cases of infection among NHS patients, and cases yet to be diagnosed, generally have their origins in treatment before those critical dates. Unless the infection is picked up incidentally during health screening or following detection of abnormal liver biochemistry in a blood test taken for an unrelated reason, and because the clinical course of NANB Hepatitis/HCV infection is asymptomatic in most cases, the infection may not come to medical attention for many years until late-stage disease is reached. At that stage the patient presents with signs of chronic liver disease or a complication of cirrhosis, such as variceal haemorrhage, ascites or the development of hepatocellular carcinoma. Estimates of undiagnosed cases cannot be substantiated. An unknown number of individuals may currently be infected but remain asymptomatic. Some may be destined never to develop complications; others will progress. Knowledge of the cohort currently infected, and their prognoses, is necessarily incomplete.

16.64 Professor Thomas emphasised that doubt remained about the progression of the disease generally:

[S]ome would say, even now, we do not really know the factors that determine the rate of progression and, for instance, in Italy Hepatitis C has a much worse prognosis to what you see in northern Europe ... and ... that's arguably related to all the other factors ... how much alcohol you take, the genetic factors, whether there is co-infection with other viruses, all manner of things.

So I don't think this uncertainty about the natural history that was prevalent between 1978 and 1985 has changed massively. I think we are still wondering: is it 20 per cent or 40 per cent that will develop cirrhosis? All we can deduce from these studies is that some people in the context of normal life ... where we eat and drink ... some people have severe liver disease. But how many, that's an open question still because none of the studies ... are statistically significant. There isn't a large enough sample of unselected cases.[93]

16.65 There have, however, been advances in knowledge of HCV infection, as shown in Chapter 13, Knowledge of Viral Hepatitis Now. Developments since about 1997 have involved laboratory research, by Dr Graeme Alexander and others, on the effect of ageing (measuring people's biological age)[94] and outcome for patients. 'Telomeres', pieces on the ends of DNA which act a bit like the piece of plastic on the end of a shoelace, prevent the DNA from 'fraying' and being damaged. There is a relationship between progressive degradation of DNA, as the telomeres shorten with age, and the development of age-related diseases such as cancer, cardiovascular disease and strokes. It is now known that the same mechanism affects HCV-positive patients, once they reach a certain biological age. They become unable to mount an immune response to infection. The immune system begins to be impaired at around age 60 and cannot cope with Hepatitis C as the virus takes a stronger grip.[95]

16.66 On the basis of the evidence as a whole on this topic, one would anticipate that a person, infected with HCV after attaining an age at which deterioration in the structure of DNA had progressed sufficiently to damage the DNA's capacity to defend itself against disease, will progress relatively rapidly from infection to cirrhosis and then to liver failure. The 'biological age' of an individual is likely to vary, and Dr Alexander's reference to age 60 might be unduly alarmist in many cases. After that age, however, the epidemiological evidence appears to be clear.

16.67 In epidemiological terms, Hepatitis C is known to have affected people to some extent in the mid-20th century. However, there is now scientific evidence that it affected the general population in many parts of the world long before that.[96] Since the mid-1980s there has been intensive research into its history and genetics. Research into the genetics of HCV by Professor Peter Simmonds of Edinburgh University has developed methods of classifying sub-types of the virus and effectively constructing an evolutionary tree for the virus showing how the various genotypes and sub-types now recognised have developed and diverged over time. His research has now demonstrated that HCV is a member of a very ancient group of viruses.[97] The characteristics of the disease caused by this virus were, however, quite unknown until the end of the twentieth century.

16.68 At the beginning of the oral hearings of this Inquiry in March 2011, the isolation and culture of one type of the complete Hepatitis C virus had been reported.[98] The position in 2011 was explained by Professor Willem van Aken when he gave evidence.[99] Almost 100% of the genomic composition of the virus had been identified by the end of the 1980s but the virus as a whole had not been isolated. It could not be reproduced by culturing (growing in appropriate nutrient substances) and one could therefore not add a known quantum of virus to plasma and submit it to inactivation to see how much virus was destroyed. However, knowledge of almost the whole genomic composition of HCV enabled scientists to make comparisons with other viruses and to select viruses with similar genomic characteristics, such as pestiviruses and togaviruses. These could be used as 'indicator viruses' or proxies for HCV. Knowledge of the genomic composition of HCV sufficient for this purpose was not achieved until around 2000. Reports of the isolation of specific sub-types of particular genomes have been published in the last ten years and there have been significant developments in the treatment of HCV infection as a result.[100]


16.69 The state of knowledge of HCV, and the natural history of the disease, discussed in Chapter 13, Knowledge of Viral Hepatitis Now, had not reached maturity in the early 1990s. Professor Thomas' evidence relating to the scientific basis of Chiron's discoveries reflected the results of continuing research over many years.

16.70 It can be concluded, however, that:

  • There was no generally accepted view prior to 1985 that NANB Hepatitis had other than a generally benign prognosis.
  • 1985 was a turning point: this was when information began to emerge that would lead to changing views.[101]
  • From 1985 it became increasingly understood that NANB Hepatitis infection could be associated with serious disease, progressing to cirrhosis in a significant proportion of cases, and to liver failure and ultimately hepatocellular cancer, albeit rarely.
  • The introduction of Interferon therapy from 1989 provided a focus for wider understanding of the characteristics and natural history of HCV infection.
  • The science of genetics has been fundamental to the discovery of characteristics of HCV.
  • Diagnostic techniques, using model viruses based on genetic analysis, became available at the end of the twentieth and the beginning of the twenty-first century.

16.71 The current understanding of Hepatitis C is necessary background to a proper appreciation of the accounts of patients and witnesses of experiences of infection with the virus. Depending on the route of transmission, recipients of blood and blood component transfusions are highly likely to have been infected before September 1991 and haemophilia patients to have been infected before October 1984 (patients treated with Factor IX) or April 1987 (patients treated with Factor VIII).

1 A surrogate marker is a directly measurable physical entity (usually measured in a blood test) that has a statistical association (correlates) 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.

2 Proteins synthesised in liver cells, normally present in low levels in the blood, which become elevated when the liver is disordered by virus infection or other disorders of the liver.

3 Schimpf, 'Liver Disease In Haemophilia', The Lancet, 1986; 323 [LIT.001.0341] at 0342

4 Hay et al, 'Progressive liver disease in haemophilia: an understated problem?', The Lancet, 1985, 1495-98 [LIT.001.0335]

5 Aledort et al, 'A Study of Liver Biopsies and Disease Among Haemophiliacs', Blood, 1985; 66:367-372 [LIT.001.0505]

6 Webster et al, 'Non-A, Non-B Hepatitis After Intravenous Gammaglobulin', The Lancet, 1986:322 [LIT.001.0341]. First reported in 1984 by Lever et al (including Webster), 'Non-A, Non-B hepatitis occurring in agammaglobulinaemic patients after intravenous immunoglobulin', The Lancet, 1984; 1062-1064 [LIT.001.0449]

7 'Safer Factor VIII and IX' The Lancet, August 2 1986 [LIT.001.3846]

8 Mollison et al, Blood Transfusion in Clinical Medicine, 8th edition, 1987

9 Ibid page 774. Reference to Alter et al, 'Posttransfusion hepatitis: clinical features, risk and donor testing' in Infection, Immunity and Blood Transfusion, 1985; 47-61 [LIT.001.0811]

10 Mollison et al, Blood Transfusion in Clinical Medicine, 8th edition, 1987, page 774. Reference to Farrow et al, 'Non-A, non-B hepatitis in West London', The Lancet, 1981: 982-984 [LIT.001.3904]

11 Mollison et al cited Alter et al, 'Posttransfusion hepatitis: clinical features, risk and donor testing', Infection, Immunity and Blood Transfusion, 1985, 47-61 [LIT.001.0811] in support of this statement.

12 Mollison et al, Blood Transfusion in Clinical Medicine, 8th edition, 1987; 774-75

13 Ibid page 775

14 Gillon and McClelland, 'Autologous blood transfusion', British Medical Journal, 1987; 294:441 [LIT.001.0218]

15 Alter et al, 'Posttransfusion Hepatitis: Clinical Features, Risk and Donor Testing' in Infection, Immunity and Blood Transfusion, 1985, 47-61 [LIT.001.0811]

16 Preliminary Report, paragraph 9.47

17 Alter, 'Transfusion-associated [NANB] hepatitis: the first decade', Viral Hepatitis and Liver Disease, 1988; 537-542, Alan R Liss, New York [PEN.018.1551] at 1555. See the Preliminary Report paragraphs 9.54 and 9.55 for further material relating to this symposium

18 Preliminary Report paragraphs 9.61 to 9.65

19 Extract from the Report of the Committee of Experts on Blood Transfusion and Immunohaematology -SP-HM- 10th Meeting - Rome 19-22 May 1987 [SNB.001.9445]

20 News Release dated 10.05.88 from Chiron Corporation announcing the cloning of the NANB Hepatitis virus [PEN.016.0290]

21 Scientific details of the discovery were not published until April 1989: Choo et al, 'Isolation of a cDNA clone derived from a blood-borne non-A non-B viral hepatitis genome', Science, 1989; 244:359-362 [LIT.001.0629] and Kuo et al, 'An assay for circulating antibodies to a major etiological virus of human non-A, non-B hepatitis', Science, 1989; 244:362-364 [PEN.017.2764]

22 'Candidate cause identified of non-A, non-B hepatitis'; Nature, 19 May 1988 [SGH.002.8036]

23 Alter et al, 'Photochemical decontamination of blood components containing hepatitis B and non-A non-B virus', The Lancet, 1988; 1446-50 [LIT.001.3984]

24 See Preliminary Report paragraphs 9.98 and 9.99 for further information on this issue.

25 Memo [SGH.002.4672] at 4673

26 'Chronic liver disease and haemophilia', The Lancet, 1988; 1465-66 [LIT.001.3838]

27 Reference was made to the following reports: (1) Lesesne et al, 'Liver biopsy in hemophilia A', Annals of Internal Medicine, 1977; 86:703-707 [LIT.001.3712]; (2) Preston et al, 'Percutaneous liver biopsy and chronic liver disease in haemophiliacs', The Lancet, 1978; 592-594 [LIT.001.0387]; (3) Spero et al, 'Asymptomatic structural liver disease in hemophilia', New England Journal of Medicine, 1989; 293:1373-78 [LIT.001.0177]; (4) Mannucci et al, 'Nonprogressive course of [NANB] chronic hepatitis in multitransfused hemophiliacs', Blood, 1982; 60:655-658 [LIT.001.0543] and (5) Stevens et al, 'Liver disease in haemophiliacs: an overstated problem?', British Journal of Haematology, 1983; 55:649-655 [LIT.001.0008]

28 Hay et al, 'Progressive liver disease in haemophilia: an understated problem?', The Lancet, 1985; 1495-98 [LIT.001.0335]

29 Schimpf, 'Liver disease in haemophilia', The Lancet, 1986; 323 [LIT.001.0341] at 0342

30 Miller et al, 'Non-invasive investigation of liver disease in haemophiliac patients', Journal of Clinical Pathology, 1988; 41:1039-43 [LIT.001.3840]

31 'Chronic Liver Disease and Haemophilia', The Lancet, 1988; 1465-66 [LIT.001.3838]

32 Quoted in 'Hepatitis non-A, non-B virus discovered', Blood Bank Week, 13 May 1988 [SNB.002.4411]

33 'Hepatitis non-A, non-B virus discovered', Blood Bank Week, 13 May 1988 [SNB.002.4411] at 4412

34 Day 67, page 90

35 Choo et al, 'Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome', Science, 1989; 244:359-362 [LIT.001.0629]

36 Kuo et al, 'An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis', Science, 1989; 244:362 [PEN.017.2764]

37 Serum is plasma with the clotting factors removed to avoid complications of clotting during the viral extraction process.

38 Professor Thomas' report on Hepatitis C [PEN.017.1071]

39 Professor Thomas - Day 52, pages 21-22

40 Ibid pages 22-23

41 Ibid page 29

42 Ibid pages 22-24

43 Ibid pages 24-26; Professor Tedder - Day 49, page 40 for terminology

44 Professor Thomas - Day 52, page 36

45 Ibid page 28

46 The process referred to as 'titration'.

47 Professor Thomas - Day 52, pages 26-28

48 Chiron Corporation and Others v Murex Diagnostics Ltd and Others and Chiron Corporation and Others v Organon Teknika and Others (1996) R.P.C. 535. The scientific background to the discovery is more fully set out in Lord Justice Morritt's judgment, from page 589. Professor Thomas, who gave evidence at the trial, commented on the novelty of granting a patent for a natural sequence: Day 52, pages, 28-29. He also expressed reservations about claims extending the scope of the patent to the whole virus, since the Chiron artefact lacked the 3 prime coded region essential for replication: Day 52, pages 37-38. However, detailed analysis of the validity of the patent is beyond the scope of this Report.

49 Choo et al, 'Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome', Science, 1989; 244: 359-362 [LIT.001.0629] at 0631

50 Professor Thomas' report on Hepatitis C [PEN.017.1071]

51 As noted in Chapter 13, Knowledge of Viral Hepatitis Now, HCV exhibits considerable genetic heterogeneity. Seven distinct genotypes of HCV have been identified.

52 Professor Hayes - Day 78, pages 46-47

53 Ibid pages 47-48

54 Sherlock, S. Diseases of the Liver and Biliary System, 8th edition, 1989, page 301

55 Ibid page 326

56 Ibid page 327

57 Ibid page 367

58 Zuckerman, A, 'Unresolved Issues in Non-A Non-B Hepatitis' [SNB.001.9490]

59 Ibid [SNB.001.9490] at 9492-93

60 Ibid [SNB.001.9490] at 9493

61 Minutes [SNB.001.9416]. The background to the setting up of ACVSB is set out in Chapter 31, The Introduction of Screening for Hepatitis C, paragraphs 31.28-31.40

62 'Non-A, Non-B Hepatitis' ACVSB 2/7 [SNB.001.9483]

63 Ibid [SNB.001.9483]

64 'Will the real hepatitis C stand up?', The Lancet, 1989: 307-308 [LIT.001.3848]

65 'Dilemma on Virus Blood Test', The Guardian, 24 August 1989[SGH.002.8010]

66 'Doctor Says Hepatitis Blood Tests Could Cost Millions', The Scotsman, 25 August 1989 [SGH.002.8007]

67 Memo [SGH.002.8012]

68 Report of Meeting [SNB.001.8678]. Dr Mitchell produced a further report [SNB.002.4553]. Dr Gunson also prepared a report on the Rome meeting. Dr Gunson's original report [SNB.006.1456] was considered at the 3rd meeting of the ACTTD on 9 October 1989 and a revised version of his report was considered at the 4th meeting of the ACVSB on 6 November 1989 [SNF.001.1383] at 1401.

69 Dr Mitchell's report of the incidence of NANB Hepatitis at 10% was grossly inflated, if intended. A more accurate estimate would have been 1%.

70 The background to the setting up of ACTTD is set out in Chapter 27, Surrogate Testing for non-A, non-B Hepatitis.

71 Report [SNB.006.1456] at 1460

72 Minutes [SNB.001.8770] at 8772; Draft Report [SNB.001.8779]

73 Fourth Draft Report (extracts) [SNB.001.8803]

74 Professor Thomas - Day 53, page 38. 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. See Chapter 35, An Investigation Into the Steps Taken to Identify the Individuals who were Infected (Look-back).

75 Press release [SNF.001.2191]

76 Letter [SGH.003.1055]

77 APPHG paper Divided Nations: Tackling the hepatitis C challenge across the UK [LIT.001.4538]

78 Ibid [LIT.001.4538] at 4549. Professor Goldberg is a Consultant Epidemiologist at Health Protection Scotland and Honorary Professor of Public Health at Glasgow University.

79 Chapter 24, Viral Inactivation of Blood products for Haemophilia Therapy 1985-1987, paragraph 24.9 and paragraphs 24.157-24.159.

80 Professor Thomas - Day 52, page 80

81 Chapter 31, The Introduction of Screening of Donated Blood for Hepatitis C, paragraph 31.248

82 Confronting the silent epidemic: a critical review of hepatitis C management in the UK [LIT.001.4801] at 4814

83 Ibid [LIT.001.4801] at 4819

84 Ibid [LIT.001.4801] at 4823

85 Professor Thomas - Day 53, pages 9-10

86 Professor Thomas - Day 52, page 119

87 Professor Thomas - Day 53, pages 41-43; Hay et al, 'Progressive liver disease in haemophilia; an understated problem?', The Lancet 1985; 1:1495-97 [LIT.001.0335]

88 Currently Emeritus Professor in Hepatology at Imperial College, London.

89 Professor Thomas - Day 52, page 146

90 Bamber et al, 'Clinical and histological features of a group of patients with sporadic non-A non-B hepatitis', Journal of Clinical Pathology, 1981; 34:1175-80 [LIT.001.0759]

91 Professor Thomas - Day 53, page 40

92 Professor Thomas - Day 52, page 76; Professor Thomas' report [PEN.017.1071] at 1077. And see, for example, 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]

93 Professor Thomas - Day 52, pages 138-139

94 'Biological age' is a measure of how well or poorly a given individual's body is functioning relative to their calendar ('chronological') age. It measures how old a person's body is compared to what we would expect from an 'average' body at that age.

95 Dr Alexander - Day 4, pages 42-44 and 46-47

96 Professor Goldberg - Day 6, page 96

97 Dr Gillon - Day 6, page 20

98 See Chapter 13, Knowledge of Viral Hepatitis Now, paragraph 13.20.

99 Day 2, pages 29-34

100 See Chapter 13, Knowledge of Viral Hepatitis Now, generally for discussion of the progress in treatment.

101 Professor Thomas - Day 52, page 146

17. Blood and Blood Products Management >