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2.1 This Inquiry is primarily concerned with the risks of infection with the Hepatitis C virus and with HIV/AIDS. The characteristics of those diseases have become much better understood, but the diseases have not generally changed over time. A person becoming infected with HIV now is infected with the same virus that affected the first patients identified as suffering from AIDS in the early 1980s. But current knowledge includes information that was not and could not have been available at certain critical periods in the past. Current knowledge can provide a measure of the deficiencies in knowledge at previous stages in the history of the relevant diseases, and so help avoid the essential error, to which historical analysis is exposed, of attributing to practitioners of earlier generations knowledge that was not available to them, and of judging them with hindsight by reference to it.

2.2 Further, actual risk and the perception of risk often differ. During the early years of use of Cryoprecipitate and factor concentrates the risk of post-transfusion hepatitis was recognised by clinicians and scientists. But the common perception was of diseases that were generally mild. While the incidence of the risk came to be recognised as high, the severity of the ensuing consequences was thought to be low. The qualitative assessment was wrong in fact. But it cannot be inferred from that error alone that the assessment was inappropriate, or unfounded, in the light of generally accepted knowledge and understanding of the diseases at that time.

2.3 Indeed, it would be wrong to assume now that current knowledge is either comprehensive in its scope, or definitive in any other respect. The common feature of hepatitis viruses is that the diseases attack the liver. There may be other viral agents that have that characteristic but that are yet to be identified. There may be factors that will lead to the differentiation of sub-types of infection within current categories. It is clear that that has been a feature of the history of developing knowledge to date. There is no reason to believe that the future will be different. In attempting to set out the understanding of the diseases that posed risks to NHS patients, the current state of knowledge is dealt with first, as a point of reference, but it is not to be inferred that what is now known is a measure of what was known from time to time over the reference period for the Inquiry. For this reason an attempt is also made to describe the state of knowledge about the biology, serum markers, symptoms and natural history of the Hepatitis B and Hepatitis C (formerly Non-A Non-B) viruses from the early 1970s, and of HIV/AIDS from 1981, to the present day.

The Hepatitis viruses

2.4 The liver has two broad functions – filtration and synthesis. The liver filters all digested products. In its synthetic function, the liver uses the absorbed products of digestion (including proteins, carbohydrates, fats, and vitamins) to synthesise most of the proteins and other products used by the body. So, most of the ‘factors’ that are engaged in haemostasis are synthesised by the liver. If the liver is inefficient, as in serious liver disease, then synthesis of clotting factors may be impaired, regardless of other influences.

2.5 Hepatitis (literally ‘inflammation of the liver’) has many causes, including toxins (especially alcohol), autoimmune hepatitis (a group of diseases in which the body’s immune system attacks liver cells), other infections, and several viruses. The hepatitis viruses existed throughout the world before the reference period, independently of the surgical and therapeutic use of blood and blood products. The diseases caused by hepatitis viruses have been and are now contracted and suffered by individuals worldwide who have never received blood or blood products. In particular, the disease now known as Hepatitis C affected individuals long before the development of modern transfusion medicine or the introduction of therapeutic blood products and long before the virus causing it was identified. Similarly, cases of HIV/AIDS probably occurred sporadically among travellers to Africa decades before the disease was described in the United States of America (USA) in the early 1980s. The manifestations of disease, the signs, symptoms, natural history and complications of Hepatitis C or HIV/AIDS that are recognised by the medical profession, have not been finally resolved even now: inevitably the expert perception and understanding of those manifestations have changed over time.

2.6 Viral and non-viral hepatitis diseases cause inflammation and fibrosis (scarring) of the liver. Apart from the common characteristic of attacking the liver, the manifestations of hepatitis viruses vary widely, and the long-term prognosis for patients may be uncertain for prolonged periods after infection. Viral hepatitis may resolve spontaneously or it may progress to fibrosis and cirrhosis (advanced scarring of the liver) or, within a few weeks of infection, to potentially fatal fulminant hepatic failure. In all forms of hepatitis, the picture presented by the patient may vary widely from anicteric and asymptomatic to severe and fatal disease.

2.7 There are six major identified human viruses which are known to cause hepatitis: the Hepatitis A virus, the Hepatitis B virus, the Hepatitis C virus, the Hepatitis D virus, the Hepatitis E virus and the Hepatitis G virus.[1]

Hepatitis A, E, G

2.8 The Hepatitis A virus (HAV) accounts for most cases of acute (ie lasting less than six months) hepatitis worldwide. It is a ribonucleic acid (RNA) virus. It accounts for 20–25% of clinical hepatitis in the developed world. Its spread is related to overcrowding, poor hygiene and poor sanitation.[2] It is an enteral virus acquired orally, generally following the ingestion of food or water contaminated with faeces from an individual who is infected with HAV. It occurs in the United Kingdom but is more common in other countries where sanitation is poor. Very rarely, pooled blood products have transmitted HAV.[3] But the disease has never led to chronic liver disease, and it has not been a major issue in relation to blood transfusion practice. Antibodies develop to Hepatitis A, attack the antigen that is characteristic of the infection, neutralise it and the patient becomes immune. Recovery is usually full.

2.9 The Hepatitis E virus is an RNA virus. It is similar to HAV. It accounts for sporadic and major epidemics of viral hepatitis in developing countries. The disease is orally transmitted, usually by sewage-contaminated water. The Hepatitis E virus causes a self-limited hepatitis in underdeveloped countries.[4]

2.10 The Hepatitis G virus is a recently identified RNA virus. A direct association between the virus and liver pathology is still lacking and it is therefore unclear whether the Hepatitis G virus is a virus which causes hepatitis. The highest prevalence rates are in Thailand, Vietnam and Africa while China, Japan and the USA have low prevalence rates. The virus is frequently found in populations who are at risk for blood-borne or sexually transmitted viruses and there is also evidence of vertical transmission from mother to infant. Because of shared modes of transmission, many patients who have the Hepatitis G virus are co-infected with other blood-borne viruses, such as Hepatitis C, Hepatitis B and HIV.[5]

Hepatitis D

2.11 The Hepatitis D virus is a blood-borne virus and only affects those people who are infected with the Hepatitis B virus. It is an RNA virus. Dual infection with the Hepatitis B virus and the Hepatitis D virus results in progressive liver disease and increased risk of hepatocellular carcinoma.[6] The southern Mediterranean, the Far East and South America are areas of moderate or high incidences of the Hepatitis D virus.[7]

Hepatitis B

2.12 The Hepatitis B virus (HBV) is a deoxyribonucleic acid (DNA) virus which is present in bodily fluids, such as blood, saliva, semen and vaginal fluid. Transmission may be vertical – that is, infection of a newborn or infant child usually by a chronically infected mother (chronic infection is defined as when the hepatitis viral infection persists for more than six months). Horizontal transmission routes (blood-borne) include blood transfusion and blood products, the use of contaminated needles medically or by drug addicts, exposure in dialysis units, tattooing and sexual contact.[8] The natural course of chronic infection is variable.

2.13 In acute HBV infection, Hepatitis B serum contains antigen particles (HBsAg) which are excess viral protein.[9] HBsAg particles appear in the blood about six weeks after infection and disappear by three months except in a carrier state (when the patient continues to have viral particles in the blood).[10] The body mounts a normal immune response and recovers. Symptoms occur usually six to ten weeks after infection. Jaundice may last three or four weeks. The patient feels weak and lethargic. Recovery is complete within one to four months, after which the patient develops immunity, marked by antibodies to the virus in the blood (anti-HBs, anti-HBc) and becomes a healthy non-carrier. The virus (as distinct from the antibody) is cleared. About three to four per cent of healthy adults, however, develop fulminant hepatitis and about 20% of these may die from the illness, usually within a month of infection, as a result of liver failure.

2.14 The clinical course of Hepatitis B is now known to differ in different groups of patients. In infants, who have an incompletely developed immune system, infection with HBV – often vertically from the mother – frequently leads to incomplete clearance of the virus and subsequent chronic infection and chronic liver disease. This sequence of events also occurs in a fairly small minority of infected adults. Those who are chronically infected with the virus are usually infectious to others, via blood-borne routes.

2.15 Persons chronically infected with HBV therefore have an increased risk of cirrhosis and of developing hepatocellular carcinoma compared to uninfected patients or those who have had an acute infection and cleared the virus.[11] Cirrhosis is characterised by long-standing irreversible damage to the liver. When the liver is damaged – whether by viruses or alcohol or other ‘insults’– it begins by regenerating, over a period of years. This process of damage and regeneration, together with scar formation in the liver, leads to serious distortion of the normal appearance and ‘architecture’ of the liver. In turn this leads to a reduction in the function of the liver and obstruction to the normal flow of blood through the liver. Although the liver is supplied by a major artery, it is the only organ in the body to have a major low-pressure blood supply – the portal circulation – which effectively drains all the blood which has supplied the whole digestive system from stomach to bowel. If the liver is scarred and disorganised, as in cirrhosis, there is back pressure on this low-pressure ‘portal’ system and blood tries to find another way back to the heart in order to bypass the liver. This may lead to the appearance of varicose veins in the lower gullet and stomach. These may burst causing very severe life-threatening haemorrhage. Alternatively this back pressure on the portal circulation can lead to the accumulation of fluid on the abdomen (ascites). Long-standing cirrhosis predisposes to the development of cancer in the liver. There is about a two to four per cent chance every year of a patient with cirrhosis, particularly if caused by a hepatitis virus, developing hepatocellular cancer.

2.16 The highest prevalence rates of infection are in Southeast Asia, China, and Africa.[12] HBV is not common in the UK. Approximately 10% of adults contracting Hepatitis B and 90% of neonates will become carriers of HBsAg[13] and are likely to develop chronic liver disease.

2.17 The study of Hepatitis B inspired much of the fundamental research that became relevant to Non-A Non-B Hepatitis (which became known as HCV), and led to technological developments that were directly applicable in that context and in the context of HIV. Safe and effective vaccines for Hepatitis A and B are now available.

2.18 Other hepatotropic viruses are being identified and their clinical relevance is under investigation.[14] Given the capacity of viruses to mutate, and the ever increasing sophistication of scientific instrumentation and knowledge, it must be anticipated that yet further hepatitis viruses will be identified. ‘New’ hepatotropic conditions will emerge in the same way as other viral diseases such as HIV, and swine fever, have done. The range of Non-A, Non-B, Non-C viruses will remain open.

The Hepatitis C virus

2.19 An estimated 200 million people worldwide are infected with the Hepatitis C virus (HCV).[15] The virus is currently a major cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in many parts of the world. Approximately 0.8% of the Scottish population (around 37,500 individuals) are thought to be chronically infected with HCV, although many individuals have not been detected.[16] However, the true incidence and prevalence of HCV infection may well now be dropping in developed countries. There are two reasons for this (i) HCV is now better understood, and successful treatment is available, and (ii) the cohort of infected individuals, particularly those infected via intravenous (IV) drug abuse in the 1980s and early 1990s as well as those infected by transfusion of blood or blood products before 1991, is washing through the system.

2.20 Cases of HCV may have been very rare in the UK until the Second World War. The disease was always more common in some countries than others. As the disease became more common through increasing medical and non-medical use of needles, blood transfusions and other means its incidence varied. Within Europe, Mediterranean countries tended to have a higher incidence of HCV infection. In some cases, the cause became apparent. In Southern Italy, an intensive immunisation programme after the war proved to be flawed by the use of the same needles to immunise perhaps a whole village: if one person in an area had HCV it could be passed to everyone else. HCV is thought to have been extremely rare in Scotland in the general population before the 1960s.

2.21 HCV is a member of the Flaviviridae family of viruses, which includes yellow fever virus and dengue fever. It is an RNA virus. RNA viruses mutate more than DNA viruses making RNA viruses harder for the body’s immune system to locate and destroy, and making development of vaccines much harder. There is still no vaccine against HCV. There are several genetic variants of HCV, known as genotypes, based on the sequence similarities of complete genomic sequences. Currently, seven genotypes, numbered 1 to 7, are recognised.[17] Each genotype is divided into several subtypes, numbered a, b, c, d etc, in order of their discovery. The prevalence of genotypes varies in different parts of the world. Types 1a and 1b are the most common, accounting for 60% of global infections. They predominate in Northern Europe (including the UK), North America and in Southern and Eastern Europe and Japan, respectively. Type 2 is less frequently represented than type 1. Type 3 is endemic in South-East Asia and is variably distributed in different countries. Genotype 4 is principally found in the Middle East, Egypt and Central Africa. Type 5 is exclusively found in Africa and the Middle East. In the UK, genotype 1 is the most common, followed by genotype 3 and then genotype 2. The specific genotype does not significantly alter the severity of the disease but it does affect the likelihood that an infected person will respond to treatment.

2.22 The classification of genotypes initially resulted in different classification systems and caused considerable confusion and difficulty in comparing results from different research groups.[18] By 1994, six major genotypes were recognised by Scots workers. In 2001 a study carried out in the Trent administrative health area used a classification system of five genotypes.[19] Subject to differences in classification, the wide distribution of genotypes in the Scots study and in the Trent study suggests that genotype may not, in general, be a reliable guide to the geographical source of the blood from which infection is contracted. The most widely distributed genotypes (1, 2 and 3) occur in Scotland and in the Trent area. In addition, most haemophilia patients who are infected have HCV of two or three genotypes, which would support the notion of infection from more than one source of HCV, and further confuses the picture. In the Scottish study of 1994, the authors observed that any attempt to interpret the geographical differences in distribution of genotypes was hampered by ignorance surrounding the method of virus transmission. For present purposes, genotype would appear to be an unreliable indicator of whether blood products associated with the transmission of infection were imported into the UK or manufactured from domestic donor blood.

2.23 Hepatitis C is extremely resilient: the virus can survive outside the body in a droplet of blood for up to three months.[20] HCV is very rarely spread by sexual contact. Very rarely it is transmitted by vertical means such as from mother to child. Needle-stick injuries, tattooing, sharing toothbrushes and razors may also transmit HCV. By far the most common apparent routes of infection are blood transfusion and IV drug abuse (due to shared needle use). Transmission by blood transfusion and blood products, including Factor VIII, Factor IX, fibrinogen and cryoglobulin has been well documented. The means by which HCV infection was acquired in a particular individual is not apparent in up to 20% of those infected in the UK.

2.24 In the 1960s Cryoprecipitate clotting factor products manufactured from pooled plasma containing HCV came into use, increasing the spread of the disease. The use of clotting factor concentrates made from thousands of blood donations in the 1970s increased the risk further. Infection spread by shared needle use came later with the spread of drug addiction. In Scotland, and in particular in cities for which data are available, IV drug abuse was uncommon in the 1960s. However, in Edinburgh for example, by 1985 IV drug abuse was common and there was an explosion in associated HCV infection (and HBV and HIV infection). This social background, contributing one aspect to the increased prevalence of HCV infection, led to the disease being stigmatised in Scotland, perhaps more than elsewhere. The generalisation was patently unfair to those who contracted the disease through medical procedures.

2.25 Since routine screening of donor blood for HCV was introduced in the UK in September 1991, transmission of the virus through blood and blood components has dramatically decreased.

2.26 Even in the case of individuals who received transfusion of blood or blood products before 1991, it would not be valid to infer that a subsequent diagnosis of Hepatitis C infection was necessarily caused by transfusion in the course of the surgical or medical procedure involved, in the absence of other circumstantial evidence. The necessary supporting evidence may be readily provided in many cases: there may be no credible or reliable alternative explanation given the patient’s medical and social history. Alternatively, the sequence of events may be determinative: the timing and characteristics of the emerging symptoms may be compatible only with a positive diagnosis and a single causative agent or event. At the other end of the spectrum, the laboratory tests and clinical features in an individual may be so fundamentally inconsistent with the known characteristics of infection following transfusion that the only proper inference is that the viral infection was contracted independently of the surgical or medical procedure involved. There are no simple answers to the issues raised by the terms of reference.

2.27 Various tests are carried out on those suspected of having acquired HCV or in whom HCV is diagnosed. These tests are used to screen for possible infection, to confirm the diagnosis and indicate current infectivity, and thereafter in following the progression of the virus and in assessing the response to treatment.

2.28 The initial screening test for the virus looks for antibodies to HCV, and is known as the anti-Hepatitis C test (anti-HCV). Antibodies are produced by the body’s immune system in response to the virus itself. It may take some time for antibodies to appear in the blood following infection, usually eight to twelve weeks after exposure to the virus, but occasionally up to six months or more. This means that the antibody test, if taken too early after infection by HCV, may not detect exposure to the virus. A positive result, known as anti-HCV positive, shows that a person has been exposed to the virus at some time. It does not detect whether the virus is still present or whether the person is infectious.[21]

2.29 If the antibody test is positive, it is usually followed by the second test, a polymerase chain reaction (PCR) test. The PCR test detects the viral RNA in the blood and thus acts to confirm the diagnosis and determine the viral levels. If the PCR test is positive this means the person is currently infected. If the anti-HCV test is positive and the PCR test is negative, this usually indicates that a person has been infected with HCV but has subsequently cleared it and is no longer infectious. During acute Hepatitis C, before antibodies to HCV have appeared, the PCR type test may be the only effective test to establish the diagnosis.[22]

2.30 In addition to specific viral tests (for HCV or HBV) blood tests reflecting damage to the liver and its function are used. Liver function tests are a set of blood tests measuring specific proteins and enzymes to determine how well the liver is performing its various functions. As liver cells are damaged by the virus, enzymes leak into the bloodstream leading to a rise in specific enzyme levels. Liver function tests usually measure alanine amino transferase (ALT), aspartate aminotransferase (AST), alkaline phosphotase (ALP), albumin, total protein and bilirubin. However, there is not necessarily a rise in enzyme levels during the acute Hepatitis C phase.

2.31 At present the most accurate way to check the extent of damage to the liver is by way of a liver biopsy. This involves taking a small sample of liver tissue via a percutaneous needle for examination under the microscope. However, a liver biopsy is taken from a small part of the liver only, and will not necessarily show up what is happening elsewhere in the liver. There is thus a risk of sampling variation. Physical evidence of a developing disease may be absent or inconclusive.

2.32 There is presently no vaccine to prevent infection with HCV.

Symptoms of infection with the Hepatitis C virus

2.33 While the virus predominantly infects the cells of the liver, recent research has shown that HCV also affects a number of other areas of the body including, probably, the digestive system, the lymphatic system, the immune system and the brain.[23]

2.34 The clinical effects of infection with any hepatitis virus depend on the severity of the inflammation induced in the liver and on whether the virus is rapidly cleared from the liver or persists long-term.[24] Most cases of acute Hepatitis C produce no symptoms and so are not diagnosed. The only indication of infection may be transient elevation in levels of ALT, an enzyme that helps to process proteins, followed shortly by symptoms, should they occur. Less than 25% of those suffering from acute Hepatitis C suffer from overt jaundice. Jaundice can last a few days to a few months but is usually restricted to less than a month.

2.35 If there are any symptoms at all of the acute disease, they are vague and non-specific. Such symptoms may include fatigue, fever, loss of appetite, abdominal pain, nausea, and vomiting. As most of these symptoms may be attributed to other short-term infections, most people are unlikely to seek medical attention and, even if they do, most doctors are unlikely to suspect or test for HCV.

2.36 Between 15% and 30% of people clear the virus completely during the acute phase of infection. These patients may have an acute clinical illness with malaise, and the symptoms described above, and sometimes jaundice. This lasts for up to a few weeks, the patient recovers, and the infection leads to no long-term injury or illness. These individuals are subsequently not carriers of HCV itself, although they may remain anti-HCV positive. HCV very seldom causes fatal, fulminating liver failure. The remaining 70–85% of those infected who do not achieve spontaneous viral clearance, are considered to be in the chronic phase of Hepatitis C after six months of infection. In these cases the virus will remain in the body long-term and these individuals are potentially infectious to others, unless treatment is given. The course of the chronic infection varies considerably from one person to another and is very unpredictable. Some people have few or no symptoms. Often, until the later stages of the disease, the only blood abnormality that can be detected is intermittent elevation of ALT. Some people develop symptoms over differing periods of time, sometimes decades. These symptoms can include fatigue, depression, short-term memory problems, mood swings, difficulties with concentration, nausea, digestive problems, joint and muscle pains, headaches, flu-like symptoms, discomfort in the liver area, abdominal pain and itching.[25] Recent research into the brain-related symptoms, including brain scanning, has indicated that HCV probably infects cells that migrate naturally to the brain directly. It appears therefore that HCV can infect the brain and other tissues.

2.37 About 10–30% of people initially infected with HCV will develop cirrhosis within 20–30 years of infection. Of those who develop cirrhosis, between one and three per cent a year will go on to develop hepatocellular carcinoma. One third may never progress to cirrhosis or will not progress for at least 50 years.[26] It is known that factors such as heavy alcohol consumption, obesity, the metabolic syndrome including diabetes and high blood pressure, being over the age of 40 years at the time of infection, being of male gender, co-infection with the HIV and HBV viruses, all increase the rate of progression of the disease.

2.38 There was little cognisance at the beginning of the reference period of the possibility that what turned out to be HCV infection would become a matter of importance. Factors that have to be taken into account in assessing the state of knowledge and understanding include the apparent extraordinary indolence of the disease, its lack of well-defined and specific symptoms, the apparent rarity of the disease in the UK before the 1960s, and the lack of a specific blood test for HCV before about 1990.


2.39 The main aim of treatment in chronic HCV infection is to eradicate the virus and thereby to reduce the chance of subsequent progression of liver disease and the risk of hepatocellular carcinoma.[27] Treatment of HCV in its early stages, when symptoms are milder and damage is less well established, can be most beneficial for patients. Early treatment increases the chance of clearing the virus and, where clearance is not achieved, suppressing the virus and delaying progression of the disease.[28]

2.40 Drug treatment to eradicate the virus has advanced greatly in the last 15 years with success rates (defined as prolonged clearance of the virus from the patient’s body) now standing at about 50% for genotype 1 and 80% for genotypes 2 and 3.[29] Treatment has evolved over the last two decades from standard Interferon monotherapy in the mid 1990s to combination therapy of standard Interferon and Ribavirin, in the late 1990s and more recently, pegylated Interferon and Ribavirin combination therapy. Each successive treatment has led to improved virological response. New anti-viral drugs are now being developed which will be more effective and have fewer side-effects than products currently available.

2.41 Interferon is a man-made drug which mimics the naturally occurring interferon produced as part of the body’s response to a viral infection. The aim of the drug is to stop the virus multiplying and causing further liver damage. It is given by injection. Pegylated Interferon is a slow-release version of the drug which only needs to be injected once a week. Ribavirin is used against a range of different viruses including HCV. It is prescribed in tablet form and is usually taken twice a day.

2.42 The current standard treatment for mild chronic Hepatitis C is combination therapy, comprising peginterferon alfa-2a and Ribavirin or peginterferon alfa-2b and Ribavirin.[30] Combination therapy with peginterferon alfa and Ribavirin is recommended within its licensed indications for people, over the age of 18 years, with moderate to severe chronic infection with HCV.[31] Those people who cannot tolerate Ribavirin are treated with Interferon alfa monotherapy.

2.43 Those people with moderate to severe chronic Hepatitis C, genotype 2 and/or 3 should be treated with peginterferon alfa and Ribavirin for 24 weeks. For those people infected with genotype 1, 4, 5 or 6, initial treatment should be for 12 weeks. Only people who show, at 12 weeks, a reduction in viral load to less than one per cent of its level at the start of treatment, should continue treatment until 48 weeks. For people in whom viral load at 12 weeks exceeds one per cent of its level at the start of treatment, treatment should be discontinued, as it is highly likely that treatment will be ineffective.[32]

2.44 Side-effects of treatment with pegylated Interferon and Ribavirin, especially in the early stages of treatment, are wide-ranging and can be severe. After each injection of Interferon, a person may suffer flu-like symptoms. Up to one half of all people treated suffer from fatigue, headaches, pyrexia (fever), myalgia (aches and pains), insomnia and/or nausea. About one quarter of those treated suffer hair loss, arthralgia (pain in the joints), rigors, irritability, pruritus (itching), depression, dermatitis and/or decreased appetite. Some people suffer from suicidal thoughts. The dropout rates from the treatment are about 7–14%.[33]

2.45 For some people with cirrhosis who develop life-threatening complications, such as varices and hepatocellular carcinoma, liver transplantation is a late-stage option. In over 60–80% of people, found to be suitable for the operation, this major surgical procedure is successful.[34]

2.46 The recurrence rate of HCV after liver transplantation is 100%. Furthermore, the natural history of Hepatitis C is accelerated after liver transplantation. In contrast to the 30% of patients who develop cirrhosis 30 years after acquiring chronic Hepatitis C, after liver transplantation 30% of patients will develop cirrhosis in five years.[35]


2.47 Acquired Immune Deficiency Syndrome (AIDS) is a condition which arises from the progressive deterioration of the body’s immune system leaving a patient prone to opportunistic infections and malignant diseases. There is a general consensus that the condition is caused by infection with the Human Immunodeficiency Virus (HIV).

Origins and early history

2.48 The origins and early history of the condition are not entirely clear. But it seems likely that HIV is a descendant of a Simian Immunodeficiency Virus passed from chimpanzees to humans in West Africa in the early part of the twentieth century. Once passed to humans, the virus mutated to become HIV.[36] Over time, HIV spread from Africa to the West and, in particular, to the USA. Retrospective studies have indicated that the first clinical cases of AIDS in the USA appeared in 1978.[37] Testing of stored serum samples has disclosed that the first known transmission of HIV to haemophilia patients also occurred in 1978 in the USA.[38] Similar testing in the UK has shown that the first known transmission of HIV to a haemophilia patient in the UK occurred around June 1979.[39] UKHCDO data suggests that the first HIV positive tests in haemophilia patients at Scottish centres were recorded retrospectively in Aberdeen and Glasgow in 1982.[40]

2.49 The disease that would become known as AIDS was first reported in 1981 when physicians in New York, Los Angeles and San Francisco noted, in otherwise healthy homosexual men, a number of relatively rare diseases hitherto usually associated with persons suffering from some form of underlying cellular immunodeficiency.[41] Epidemiological studies carried out shortly afterwards revealed that, although homosexual men formed the largest affected group, the constellation of symptoms was also seen in injecting drug users, heterosexuals with multiple partners, and haemophilia patients treated with blood products. While various agents were initially considered as possible causes of the new disease, epidemiological investigations came to suggest that the most likely cause was a blood-borne infectious agent that was sexually transmissible.

Isolation and naming of the virus

2.50 The virus that causes AIDS was first isolated in 1983 by researchers in France.[42] The isolate came from a patient with enlarged lymph glands and was called lymphadenopathy-associated virus (LAV). It was not, however, generally accepted that this virus was the cause of AIDS until researchers in the USA reported, in 1984, on the isolation of the same virus from a number of patients with AIDS.[43] The first American isolates were named human T cell lymphotropic virus Type III (HTLV III).[44] In 1986 the virus was renamed Human Immunodeficiency Virus by the International Committee for the Taxonomy of Viruses.[45]

Biology of HIV

2.51 HIV can only replicate (make new copies of itself) inside human cells. The process typically begins when an HIV particle attaches itself to the surface of a CD4 T-helper lymphocyte cell (a type of white blood cell that plays a crucial role in maintaining the function of the human immune system). After attaching to the cell, the virus then enters the cell and converts its RNA into DNA by the use of an enzyme called reverse transcriptase.[46] The viral DNA is transported to the cell’s nucleus, where it is spliced into the human DNA. Once integrated into a cell, the virus may lie dormant within the infected cell for months, or even years.

2.52 When the cell becomes activated, however, it treats the HIV genes within it in much the same way as human genes. The result is that new HIV viral particles are formed and released, thereby starting the replication process all over again. HIV can replicate rapidly with several billion new viruses made every day in a person infected with HIV.

2.53 During replication HIV also mutates and evolves. Reverse transcriptase (by which viral RNA is converted into DNA) often makes random mistakes in the transcription of viral RNA into DNA. As a result, new types or strains of HIV (with slightly different DNA) develop in a person infected with HIV, making it harder for that person’s already compromised immune system to ‘recognise’ or to respond to and deal with the virus.

2.54 Every day, the virus destroys billions of CD4 T-helper lymphocyte cells in a person infected with HIV, eventually overwhelming the immune system’s capacity to regenerate or fight infection.


2.55 HIV is found in the blood, semen and vaginal fluid of those infected with the virus. It cannot survive for very long outside the body. The main modes of transmission are sexual intercourse, IV drug use (through the use of shared, contaminated needles), receiving a transfusion of infected blood or blood products and perinatally (ie from infected mothers to their children).

Symptoms and pathology

2.56 In the first few weeks after infection with HIV most people will experience few, if any, symptoms. Within a month or two after infection, individuals may experience a flu-like illness, including fever, headache, tiredness and enlarged lymph nodes in the neck and groin area. The symptoms usually disappear within a week to a month after their onset and are often mistaken for another viral infection such as glandular fever or influenza (flu). During this period, people are highly infectious. There then follows a period during which the body’s immune system fights back and the disease remains clinically latent.

2.57 Over time, however, the immune system eventually deteriorates to the point at which it is unable to fight off other infections. The rate of progression to symptomatic disease (ie AIDS) varies greatly from person to person and may take many years. When the disease was first reported it was estimated that only a minority of patients with HIV would go on to develop AIDS.[47] It is now known, however, that, if untreated, the vast majority of patients who contract HIV are likely to go on to develop secondary ‘opportunistic’ infections or tumours which, in the absence of treatment, are likely eventually to result in death.

2.58 The secondary infections that may develop include a variety of fungal, viral and bacterial infections of the mucous membranes and skin. However, a type of pneumonia, Pneumocystis Carinii, remains the most common life-threatening secondary infection in patients who progress from chronic HIV infection to AIDS. In addition, due to a failure of the body’s ‘immune surveillance’ of possible cancer cells, secondary cancers may develop over time, including Kaposi’s sarcoma, non-Hodgkin’s lymphoma and primary cerebral lymphoma.

2.59 The disease may also affect the nervous system with the development of cerebral toxoplasmosis (leading to the formation of abscesses in the brain), HIV encephalopathy, myelopathy and peripheral neuropathy. Patients may also suffer psychiatric disorders including depression.

2.60 Eventually, patients develop end-stage disease when they have little immunity and death becomes inevitable from one or more of the above or related conditions.


2.61 When an individual becomes infected with HIV, antibodies to the virus are produced, but unlike the case in most other infections, these antibodies have little or no ability to neutralise the virus. The antibodies are, however, used in laboratory tests as a marker for the presence of HIV. Tests which detect antibodies to HIV include enzyme-linked immunosorbent assay (ELISA) and Western blot tests. Detectable antibodies are usually produced within two to six weeks of infection, although sometimes the period may be up to three months. Accordingly, the ELISA and Western blot laboratory tests may not detect HIV antibodies in an individual who has recently been infected with HIV (ie up to three months of infection). The change to a state where antibodies are detectable is known as ‘seroconversion’.

2.62 PCR tests detect the presence of HIV itself, through detection of its genetic material, rather than the presence of antibodies to HIV. PCR testing may be undertaken to detect the presence of the virus before as well as after seroconversion, and therefore may be used in the ‘window’ between the time the individual acquired HIV infection and seroconversion (the appearance of anti-HIV in the blood).


2.63 In the early 1980s, when the HIV/AIDS epidemic began, after an initial relatively asymptomatic period lasting for a variable number of years, people were unlikely to live longer than a few more years from the development of AIDS. Today, the prognosis for those infected with HIV is much better as a result of the availability of antiretroviral medication. There are five main groups of antiretroviral drugs presently available to treat the disease, each of which attacks the virus in different ways.[48] If only one drug was taken, HIV would quickly become resistant to it and the drug would stop being effective. Therefore, two or more antiretroviral drugs are prescribed at the same time, thereby reducing the rate at which resistance will develop and making treatment more effective in the long term.

2.64 These treatments do not cure people of HIV or AIDS and the virus is not completely eliminated from the body. Rather, the drugs suppress the virus either by stopping the virus from replicating itself, or by preventing it from binding to or entering human immune cells. Suppression of the amount of HIV in the body stops further weakening of the immune system and allows it to recover from any damage that HIV might already have caused, thus allowing people infected with HIV to lead longer and healthier lives.

2.65 People undergoing treatment can still transmit the virus, however, and must continuously take antiretroviral drugs in order to maintain their health. There is currently no vaccine to prevent HIV infection nor is there a cure for HIV/AIDS.

Numbers of people affected

2.66 In 2006, the 25th anniversary of the emergence of AIDS in Western countries, there were close to 40 million people around the world living with HIV and over 20 million people had died. In the UK since 1996, there have been around 30,000 HIV diagnoses. As at May 2009, as reported to the National Haemophilia Database, 1382 patients with bleeding disorders in the UK were known to have been infected with HIV.[49] Of those, 72 were registered to Scottish centres. It has been reported that 12 patients in Scotland contracted HIV as a result of a blood transfusion.[50] Other data suggest that the cumulative total of HIV-infected haemophilia patients registered in Scotland to 30 September 1999 was 87.[51] Resolution of a more precise figure will have to await the final outcome of the Inquiry.


2.67 It has to be emphasised that the information contained in this chapter reflects the state of knowledge current at the date of publication of this preliminary report. Almost none of this would have been known before 1991.

[1] Schiff, Eugene R., Sorrell, Michael F., Maddrey, Willis C., Schiff’s Diseases of the Liver, 10th Edition, 2007

[2] Sherlock, Diseases of the Liver and Biliary System, 8th Edition, p308

[3]Oxford Textbook of Medicine, 4th Edition, volume 1, chapter 14.20.1: In late 1992 there were reports of HAV transmission associated with solvent detergent treated Factor VIII. The issue became controversial [SNB.007.8091].

[4] Zuckerman, A., Thomas, H., Viral Hepatitis, 2nd Edition

[5] Schiff, Eugene R., Sorrell, Michael F., Maddrey, Willis C., Schiff’s Diseases of the Liver, 10th Edition, 2007

[6] Schiff, Eugene R., Sorrell, Michael F., Maddrey, Willis C., Schiff’s Diseases of the Liver, 10th Edition, 2007, chapter 26

[7]Oxford Textbook of Medicine, 4th Edition, Volume 1, chapter 14.20.1

[8]Oxford Textbook of Medicine, 4th Edition, volume 1, chapter 14.20.1

[9] Sherlock, Diseases of the Liver and Biliary System, 8th Edition, p313

[10] Sherlock, Diseases of the Liver and Biliary System, 8th Edition, p314

[11] Schiff, Eugene R., Sorrell, Michael F., Maddrey, Willis C., Schiff’s Diseases of the Liver, 10th Edition, 2007, chapter 26

[12] Schiff, Eugene R., Sorrell, Michael F., Maddrey, Willis C., Schiff’s Diseases of the Liver, 10th Edition, 2007, chapter 26

[13] Sherlock, Diseases of the Liver and Biliary System, 8th Edition, p319

[14]Oxford Textbook of Medicine, 4th Edition, volume 1, chapter 14.20.1

[16] Scottish Intercollegiate Guidelines Network, ‘Management of hepatitis C: A national clinical guideline’, December 2006 []

[18] McOmish et al, ‘Geographical distribution of hepatitis C virus genotypes in blood donors: an international collaborative survey’, Journal of Clinical Microbiology, April 1994; 32(4) 884 [LIT.001.1292]

[19] Mohsen, ‘The Epidemiology of Hepatitis C in a UK Health Regional Population of 5.12 million’ Gut, 2001; 48; 707-713 [LIT.001.1094]

[22] Zuckerman, A.,Thomas, H., Viral Hepatitis, 2nd Edition, p340

[24]Oxford Textbook of Medicine, 4th Edition, volume 1, chapter 14.20.1

[25] []

[26] National Institute for Clinical Excellence, ‘Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C’, Technology Appraisal 75, January 2004 []

[27] National Institute for Clinical Excellence, ‘Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C’, Technology Appraisal 75, January 2004 []

[30] National Institute for Clinical Excellence, ‘PegInterferon alfa and ribavirin for the treatment of mild chronic hepatitis C’ Technology Appraisal Guidance 106, paragraph 1.1 []

[31] National Institute for Clinical Excellence, ‘Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C’, Technology Appraisal 75, January 2004, paragraph 1.1 []

[32] National Institute for Clinical Excellence, ‘Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C’, Technology Appraisal 75, January 2004, paragraph 1.1 []

[33] National Institute for Clinical Excellence, ‘Interferon alfa (pegylated and non-pegylated) and ribavirin for the treatment of chronic hepatitis C’, Technology Appraisal 75, January 2004, paragraph 2.13

[35] Schiff, Eugene R., Sorrell, Michael F., Maddrey, Willis C., Schiff’s Diseases of the Liver 10th Edition, 2007

[36] (1) Gao et al, Nature, 1999;397:436 [LIT.001.1178], (2) Bailes et al, ‘Hybrid origin of SIV in chimpanzees’, Science, 2003;300:1713 [LIT.001.1184] and (3) Wolfe et al, ‘Naturally acquired simian [LIT.001.1185] retrovirus infections in Central Africa Hunters’, Lancet, 20 March 2004;363:932. It has been postulated that the virus crossed from chimpanzees to humans as a result of hunters eating infected animals or getting the blood of infected animals into cuts or wounds

[37] Jaffe et al, ‘The acquired immunodeficiency syndrome in a cohort of homosexual men: a six-year follow-up study’, Annals of Internal Medicine, 1985;103:210-214 [LIT.001.1060]. In the UK, it appears that the first clinical case of what was to become known as AIDS may have been reported as early as 1960: Williams et al, ‘Cytomegalic inclusion disease and Pneumocystis carinii infection in an adult’, Lancet, 29 October 1960:951-955

[38] Evatt et al, ‘Antibodies to human T-cell leukaemia virus-associated membrane antigens in hemophiliacs: evidence for infection before 1980’, Lancet, 1983;ii:698 [LIT.001.1196] and Machin et al, ‘Seroconversion for HTLV-III since 1980 in British haemophiliacs’, Lancet, 1985;i:336 [LIT.001.1195]

[39] Darby et al, ‘Mortality before and after HIV infection in the complete UK population of haemophiliacs’, Nature, 7 September 1995;377:79-82[LIT.001.1301]

[40] UKHCDO data: see appendices

[41] Pneumocystis pneumonia – Los Angeles MMWR 5 June 1981; 30, 250-252 [LIT.001.1026]; Hymes et al, ‘Kaposi’s sarcoma in homosexual men: A report of eight cases’, Lancet, 1981;2:598-600 [LIT.001.0768] and ‘Kaposi’s Sarcoma and Pneumocystis Pneumonia among homosexual men – New York City and California’, MMWR, 4 July 1981;30(4):305-308 [LIT.001.0766]

[42] Barré-Sinoussi et al, ‘Isolation of a T-lymphotrophic retrovirus from a patient at risk of acquired immune deficiency syndrome (AIDS)’, Science, 1983;220:868-871 [LIT.001.0058]

[43] Gallo et al, ‘Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS’, Science, 1984;224:500-503

[44] As they were the third type of virus that the researchers had found that specifically attacked the T cells of man.

[45] There are, in fact, known to be at least two main types of HIV viruses. HIV-1 is responsible for the worldwide pandemic of AIDS while HIV-2 is mainly confined to West Africa.

[46] This is so called because it works ‘backwards’ in the sense that ordinarily RNA is made using DNA as a template rather than the reverse. Viruses such as HIV are known as ‘retroviruses’ because of this unusual property. HIV is also a member of the subgroup of retroviruses known as lentiviruses (viruses with a long incubation period).

[47] In 1986, for example, a UK Government advisory body stated that only 1 in 10 people with HIV were likely to go on to develop AIDS: DHSS Advisory Committee on Dangerous Pathogens, ‘Revised guidelines on LAV/HTLV III – the causative agents of AIDS and related conditions’ [DHF.002.1456] at page 8.

[48] The main groups of antiretroviral drugs and the year in which they were first approved (by the USA Food and Drug Administration) to treat HIV are as follows: Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (1987); Protease Inhibitors (1995); Non-Nucleoside Reverse Transcriptase Inhibitors (1997); Fusion or Entry Inhibitors (2003); and Integrase Inhibitors (2007).

[49] Appendix 1 UKHCDO data

[50] Answer to Parliamentary Question 21 December 1989 [SGF.001.1248]. The same Answer reported that there had been 76 patients with haemophilia in Scotland who had tested positive for HIV.

[51] The evidence of Dr Peter Foster ( SNBTS) to the Archer Inquiry (Day 7 of the Inquiry, at pp58-60 of the transcript of proceedings) reported that 87 haemophilia patients in Scotland contracted HIV as a result of treatment with blood products. The same figure was published by the Scottish Centre for Infection and Environmental Health. See Appendix 4.

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