Retrospective cohort study of liver transplantation in the United Kingdom between 1994 and 2010: the impact of hepatitis C infection.

BACKGROUND: Liver transplantation is an important and established treatment option for chronic hepatitis C virus (HCV) related end-stage liver disease (HCV-related ESLD). This study describes trends in elective liver transplantation among persons with HCV-related ESLD. STUDY DESIGN: Retrospective cohort. METHODS: Analyses of United Kingdom (UK) Transplant Registry data for the period 1994 to 2010, with follow-up information extending to 2011. RESULTS: Annual registrations for liver transplantation increased linearly and alcoholic liver cirrhosis (2075, 24%) and HCV-related ESLD (1213, 14%) were the most common indications. HCV-related ESLD patients were mainly aged 40-49 years (32%) and 50-59 years (43%); males (76%); and of white ethnicity (74%). Overall, 75% (956/1213) received a liver transplant with a linear increase over the period (OR 1.11, 95% CI 1.08, 1.13). Pre transplant mortality was unchanged (adjusted OR 1.0, 95% CI 0.96, 1.05) and post-transplant mortality decreased in both HCV-related (adjusted OR 0.77, 95% CI 0.68, 0.88) and non-HCV-related ESLD (adjusted OR 0.82, 95% CI 0.75, 0.89) patients. CONCLUSION: The increase in demand for and receipt of liver transplants among persons with HCV-related ESLD requires coordinated efforts to increase not only organ donation, but investment in HCV prevention programmes and improved access to hepatitis C treatment services.

Hepatitis B virus transmission in pre-adolescent schoolchildren in four multi-ethnic areas of England.

The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7-11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0.26%, 95% confidence interval (CI) 0.14-0.44]. The estimated average annual incidence of hepatitis B was estimated to be 29.26/100 000 children (95% CI 16.00-49.08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5.00 and 12.49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.

Where are people being tested for anti-HCV in England? Results from sentinel laboratory surveillance.

SUMMARY: Many people infected with hepatitis C virus (HCV) are unaware of their infection and are, therefore. potentially infectious to others. To enable effective case-finding policies to be developed, an understanding of where people, and injecting drug users (IDUs) in particular, are accessing HCV antibody testing is needed. HCV antibody testing data were collected electronically from 21 sentinel laboratories in England between 2002 and 2006 in this cross-sectional study. Service types of the physician requesting the HCV test were identified and classified. Differences in people being tested in each service type and over time were investigated. Over half a million people were tested in 5 years. Whilst most testing took place in hospital, a large proportion of people were tested in community care, particularly in general practice surgeries and genito-urinary medicine clinics. Younger people were more likely to be tested in community care, and there was evidence that testing differed according to ethnic status. IDUs were tested in all parts of the health services, although the highest proportion positive were from prisons and specialist services for drug users. Testing increased between 2002 and 2005 whilst the proportion of people testing positive declined. Routine laboratory data can provide valuable information on where people are being tested for HCV. Risk exposures should be investigated and testing targeted to people at higher risk for infection. Local laboratories should review data on testing locations and proportion positive to inform local initiatives to improve testing and yield.

Diagnosis of acute hepatitis C virus infection and estimated incidence in low- and high-risk English populations.

The diagnosis of acute hepatitis C virus (HCV) infection is not straightforward; few people exhibit clinical symptoms and genome/antigen detection techniques do not indicate when infection had occurred. Here, a strategy to detect HCV RNA in the absence of antibody ('window-period') for diagnosis of acute infection is assessed. The sentinel surveillance of hepatitis testing study was used to retrospectively identify anti-HCV negative samples from high-risk individuals (2002-2003), for testing singly for HCV RNA. Additional samples were identified prospectively (2005) and tested in pools for HCV RNA. Positive samples were genotyped. Incidence and costs of adopting the pooling strategy were estimated. In the retrospective study, 8/390 (2.1%) samples were confirmed HCV RNA positive, anti-HCV negative. Prospectively, 3237 samples were tested in 325 pools. Five positive pools identified four confirmed HCV RNA positive patients (one false positive). Estimated incidence was 12.9 per 100 person-years in injecting drug users (IDUs) (retrospective study) and 3.7 per 100 person-years among drug/alcohol services and prison attendees (prospective study). Estimated costs were pound 850 per positive sample, in areas of higher risk. The yield from a window-period strategy depends upon the population tested. Pooled HCV RNA testing of anti-HCV negative samples from the current IDUs is realistic and relatively inexpensive to identify recently infected individuals.

The prevalence of hepatitis C in England and Wales.

OBJECTIVES: To estimate the background population prevalence of hepatitis C in England and Wales, observe the prevalence over time and assess the extent of infection outside of known risk groups. METHODS: Sera from residual specimens from adult patients submitted to laboratories in England and Wales were tested for anti-HCV. Testing was carried out using a cost-effective pooling strategy. RESULTS: Although the prevalence of anti-HCV was highest in 1986 (1.07%), in the multivariable analysis, prevalence did not vary significantly between the 3 periods 1986, 1991 and 1996 (P=0.14). The prevalence of infection was higher in males than in females (P=0.0013). An age-period-cohort analysis revealed a cohort effect due to a lower HCV prevalence in the most recent birth cohorts, that is, those born between the calendar years 1971-1975 and 1976-1980. CONCLUSIONS: The majority of HCV infections in England and Wales were probably acquired before 1986. Infections in younger males identified in 1996 may signify more recent acquisition by injecting drug use.

Undernotification of tuberculosis in patients with AIDS.

The purpose of this study was to establish the extent of undernotification of tuberculosis in AIDS patients resident in 2 inner London local authorities. For residents of the 2 authorities, statutory notifications of tuberculosis between 1986 and 1992 were compared, using soundex codes of surnames, sex and year of birth, with AIDS cases reported to the Public Health Laboratory Service (PHLS) AIDS Centre during the same period where TB had been recorded on the AIDS report form. In 36 of 613 AIDS cases reported as residents of the 2 authorities tuberculosis was recorded on the AIDS report form. Matching revealed that only 2 (6%) of these cases had been notified to the local authority. These results highlight the need to resolve the dilemma between concerns about patient confidentiality and the statutory requirement to notify tuberculosis so that clinical management of contacts can be undertaken and the true impact of HIV infection on the incidence of tuberculosis in the UK can be elucidated.

Leukocyte counts in falciparum malaria in African children from an endemic area.

Total leukocyte counts were done in 180 apparently healthy rural school children aged 6-12 years in a malaria endemic area in southwestern Nigeria. Total leukocyte counts and their distribution in aparasitaemic and asymptomatic parasitaemic children were similar. Total leukocyte counts, and the relationship between the density of parasitaemic and total leukocyte counts were studied in 55 consecutive children presenting with acute symptomatic falciparum malaria. Children without parasitaemia were older and had lower total leukocyte counts when compared with children with parasitaemia (7.61 +/- 4.11 x 10(9)/L Vs 9.04 +/- 5.0 x 10(9)/L), but the difference was not statistically significant (P > 0.05). In non-hyperparasitaemic children and in hyperparasitaemic children with percentage infected red cells < 10%, there was poor correlation between density of parasitaemia and total leukocyte counts. However, at > or = 10% parasitaemia, there was a positive correlation (r = 0.55; P = 0.032) between increasing parasitaemia and leukocytosis. Combination of hyperparasitaemia ( > 5% parasitaemia) and leukocytosis ( > 12 x 10(9)/L) occurred in 15% of the children and was not a poor prognostic index in the absence of other evidence of severe or complicated disease, as response to oral mefloquine was prompt. This would suggest that in African children from an endemic area, this combination is not a reliable indicator of severity or poor prognosis in falciparum malaria.

Diagnoses of, and deaths from, severe liver disease due to hepatitis C in England between 2000 and 2005 estimated using multiple data sources.

Matching individuals reported to a sentinel surveillance scheme for hepatitis C between 2000 and 2005 to individuals with a hospital episode for hepatitis C-related liver disease in the same hospitals, we estimated that the number of cases of hepatitis C-related end-stage liver disease in these English hospitals was 42% (597/419) higher than Hospital Episode Statistics (HES) would indicate. Further, matching records of hepatitis C-related deaths in HES to death certificates, we estimated that, between 2000 and 2005, the true number of deaths from hepatitis C-related end-stage liver disease was between 185% (353/124) and 257% (378/106) higher than the number recorded in routine mortality statistics. We provide estimates of under-recording that can be used to modify existing models of disease burden due to hepatitis C and provide a simple approach to improve the monitoring of trends in severe hepatitis C-related morbidity over time.

Estimating hepatitis C infection acquired in England, 1986-2000.

Hepatitis C is a global health problem and in the UK seroprevalence studies have mainly concentrated on specific high-risk groups. The aim of this study was to determine changes in the prevalence of antibody to hepatitis C virus in England using residual specimens collected between 1986 and 2000 reflecting the general population. A cross-sectional study design using a convenience collection of serum specimens from adult patients submitted to laboratories in the years 1986, 1991, 1996 and 2000 from a total of 19 laboratories around England were investigated. The main outcome was to determine anti-HCV prevalence and the average incidence occurring between 1986 and 2000 and factors associated with infection. Multivariable analysis of results from all years showed there was a significant difference in prevalence between males and females (P < 0.001), birth cohort (P < 0.001) and by health region (P < 0.001). An average of 0.72% (95% CI 0-1.65%) of those susceptible to HCV born between 1950 and 1970 were estimated to have acquired the infection between 1986 and 2000. Analysis of this convenience serum collection suggests that HCV prevalence is low in the general population, and is associated with period of birth, gender and health region. There was evidence to support a low incidence of HCV infection in those born between 1950 and 1970 over the period 1986-2000 which, at the population level, equated to a substantial burden of infection (approximately 106,000 persons). Continued surveillance and prevention targeted at injecting drug users are essential for the control of hepatitis C in the UK.

Prevalence and incidence of hepatitis C in injecting drug users attending genitourinary medicine clinics.

Surveillance reports and prevalence studies have indicated that injecting drug users (IDUs) contribute more to the hepatitis C epidemic in the United Kingdom than any other risk group. Information on both the prevalence and incidence of hepatitis C in IDUs is therefore essential to understanding the epidemiology of this infection. The prevalence of hepatitis C in specimens from the Unlinked Anonymous Prevalence Monitoring Programme collected in 1995, 1996, 1998, 1999, 2000, and 2001 was determined using residual syphilis serology specimens from IDUs attending 15 genitourinary medicine (GUM) clinics in and outside London. These specimens were tested for antibodies to hepatitis C virus (anti-HCV). Using this cross-sectional design, anti-HCV-negative specimens were tested for HCV RNA to identify incident infections during the 'window' period of infection, and thus to estimate HCV incidence. Results of the multivariable analysis showed that there was marked variation in prevalence by clinic (P<0.0001) and age (P<0.0001). Overall the majority of infections were in males and the overall prevalence in injectors declined over the study period from 36.9% to 28.7%. The annual incidence in these injectors was estimated as being 3.01% (95% CI 1.25-6.73). Over the study period HCV incidence decreased by 1.2% per year. Genotyping of the incident infections identified the most common genotype as type 1 with type 3 being more frequently seen after 1998. Of the prevalent infections, genotype 1 was the most common. The study has confirmed a higher prevalence of anti-HCV in IDUs in the London area compared to those outside London. How representative of the current injecting drug user population are IDUs attending GUM clinics is unclear. Even so, such studies allow prevalence and incidence to be estimated in individuals who have ever injected drugs and inform ongoing public health surveillance.

Hepatitis C virus: laboratory surveillance in England and Wales, 1992-2004.

Between 1992 and 2004, a total of 49,819 confirmed hepatitis C infections have been reported to the Health Protection Agency (HPA) by laboratories in England and Wales; the annual number of reports increased from 241 in 1991 to 8149 in 2004. Most reports with a known risk factor were in injecting drug users (87%, 12,438/14,221), but 71% (35,598/49,819) of the total had no reported identified risk. The age-sex distribution of the latter cases was similar to that in injecting drug users. Using names to assign ethnicity, individuals with South Asian names had an older age distribution and a different risk factor profile from non-South Asians. Using published age-specific prevalence data from 1996, it was estimated that around 28,1764 cases of hepatitis C infection exist in England and Wales, and that only 17% of these cases have been reported to the HPA. Surveillance reports continue to provide important information regarding trends in hepatitis C infection in specific risk groups.

Sentinel laboratory surveillance of hepatitis C antibody testing in England: understanding the epidemiology of HCV infection.

This paper describes sentinel laboratory surveillance of hepatitis C antibody testing in England. Demographic and test result data were supplemented by follow-up questionnaires sent to the requesting clinician. Between October 2002 and September 2003 almost 75000 anti-HCV tests were performed in eight sentinel centres. More males were tested than females and over half of those tested were aged 25-44 years. Overall 5.7% (3333/58144, range 2.8-7.7%) individuals tested positive. Follow-up questionnaire data showed that 82% (1043/1277) of the positives had injecting drug use reported as the main risk exposure. The majority of negative individuals were undergoing routine screening as recommended for specific patient groups. Most individuals were asymptomatic. Antibody prevalence was estimated to be 34% in current injecting drug users and 42% in former injectors. Comparing positives to routine national surveillance suggests that only 53% (1782/3333) of diagnosed cases were reported. Sentinel laboratory data can provide valuable supplementary data to national surveillance.

Laboratory surveillance of hepatitis C virus infection in England and Wales: 1992 to 1996.

Screening assay for antibody to hepatitis C virus (HCV) became available late in 1990 and their use has subsequently become widespread. Laboratories in England and Wales reported 5232 confirmed HCV infections to the PHLS Communicable Disease Surveillance Centre (CDSC) between 1992 and 1996. Fifty-seven per cent (2976) of reports included risk factor information, 80% of which (2382) identified injecting drug use as the main route of transmission. Thirty-one per cent of reports (1640) included clinical information: 41% (665) were asymptomatic, 57% (938) had symptoms, signs, or biochemical abnormalities of hepatic origin, and 2.2% (37) had non-hepatic conditions. To enhance these data two additional surveys have been undertaken to collect data on all anti-HCV tests performed in public health laboratories. In 1993, a retrospective survey of people tested between 1990 and 1993 revealed that the prevalence of antibody was highest (222/331 [67%]) among injecting drug users and recipients of blood or blood products (189/548 [34%]) and lower among other groups. In a prospective survey of HCV tests performed in transfusion recipients in early 1995, the prevalence of antibody was higher in those transfused before 1985 (11/418 [2.6%]) than in those transfused after 1985 (14/1441 [1.0%]). Reports of confirmed infections are a useful method of monitoring hepatitis C infection but additional data on testing are needed to interpret trends overall and in specific risk groups.

Acute hepatitis B infection in England and Wales: 1985-96.

Confirmed acute hepatitis B infections are reported to the Public Health Laboratory Service Communicable Disease Surveillance Centre by laboratories in England and Wales. These reports have been used to monitor trends in the incidence of hepatitis B virus (HBV) infection over time, and between exposure categories and age groups. Between 1985 and 1996 a total of 9252 cases of acute HBV infection were reported; the number of reports fell from 1761 in 1985 to 581 in 1996. Most infections were reported in adults aged 15-44 years [n = 7365 (80%)], and infections were more commonly reported in males [n = 6490 (70%)] than females [n = 2658 (29%)]. The probable means of acquisition was known for just over half of all adult cases [4827/8956 (54%)]. Injecting drug use was the most common exposure [n = 1901 (21%)], followed by sex between men and women [n = 1140 (13%)] and sex between men [n = 1025 (11%)]. The number of infections in injecting drug users fell in the late 1980s, but increased again from 1991 onwards. In children aged under 15 years, infections acquired by mother to baby transmission accounted for 35/170 (21%) of the total. Surveillance indicates that the incidence of acute hepatitis B infection fell in the late 1980s, probably reflecting changed behaviour in injecting drug users. An increase in the number of infections in injecting drug users since 1993 may indicate ongoing transmission that has not been contained by the introduction of needle exchange schemes or by selective vaccination.

The prevalence and genetic diversity of hepatitis C infection in antenatal clinic attenders in two regions of England.

The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinics in two regions of England was investigated to inform future surveillance and control measures. Women booking into antenatal care are routinely offered a test for immunity to rubella. Serum residues from these tests were unlinked, anonymized and archived as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP). The serum specimens were tested for anti-HCV using a cost-effective pooling strategy. After taking into account differential sampling from the UAPMP serum archive, the adjusted overall prevalence of anti-HCV was 0.43% (95% CI: 0.32-0.53) in London and 0.21% (95% CI: 0.14-0.28) in the Northern and Yorkshire region. Restriction fragment length polymorphism of amplified HCV RNA identified type 3a as the most common HCV genotype in these antenatal women. The prevalence of anti-HCV in antenatal women in the UK is low and consistent with that expected from injecting drug use.

Risk factors, clinical features and genotype distribution of diagnosed hepatitis C virus infections: a pilot for a sentinel laboratory-based surveillance.

Hepatitis C is a global public health problem. A cross-sectional survey was undertaken to determine the frequency of reported risk factors and possible transmission routes in individuals in whom HCV antibody (anti-HCV) was newly detected. Seven public health laboratories in England and Wales reported persons with positive anti-HCV tests over a three-month period (1st November 1996-31st January 1997). A questionnaire was then sent to the clinician or general practitioner (GP) who requested the test. A total of 320 laboratory reports were received from participating laboratories and 221 (69%) questionnaires were received from clinicians and GPs. Of those patients from whom a questionnaire was received (median age 36 years; males 72.9%, females 23.1%), 86% had one or more risk factors for infection reported by the clinician/GP. Injecting drug use (68%) was the main risk factor reported. Reasons for testing included being in a known risk group (65%), liver disease (19%) and blood donation (1.4%). Of the total responders, 67% were asymptomatic, and of those that had had liver function tests 50% were abnormal. The most prevalent HCV genotypes were 3a and 1a. Risk factors for HCV infection can be identified using a simple postal questionnaire to clinicians/GPs who request patient screening.

A national survey of genitourinary medicine clinic attenders provides little evidence of sexual transmission of hepatitis C virus infection.

OBJECTIVE: To determine the prevalence and genetic diversity of hepatitis C virus in genitourinary medicine clinic attenders and to assess the extent of sexual transmission of the virus. METHODS: A cross sectional, unlinked, anonymous survey in 14 genitourinary medicine clinics situated in England, Wales, and Northern Ireland. Serum specimens from genitourinary medicine clinic attenders, retained as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP) serum archive, were tested in small pools, for the presence of antibody to hepatitis C virus (anti-HCV). The main outcome measures were prevalence of antibodies to hepatitis C virus and identification of hepatitis C virus genotypes. RESULTS: Testing of 17,586 specimens from 1995 showed an adjusted prevalence of anti-HCV in genitourinary medicine clinic attenders of 1.03% (95% CI: 0.89 to 1.16) overall and 0.65% (95% CI: 0.51 to 0.78) among those who did not report injecting drug use. Prevalence in injecting drug users attending genitourinary medicine clinics was 36.9% in both 1995 and 1996. Heterosexual injecting drug users had a higher prevalence of anti-HCV than homosexual/bisexual injectors. The most common hepatitis C genotypes were types 3a and 1a. There was a high degree of concordance between genotype and serotype. CONCLUSIONS: The low prevalence of anti-HCV in genitourinary medicine clinic attenders who deny injecting drugs suggests that the majority of hepatitis C infections have been acquired in adult life, mostly by injecting drug use, and that the hepatitis C virus is rarely transmitted sexually. The use of needle exchanges may explain the relatively low prevalence observed in the injecting drug users.