Prevalence and outcome of post-transfusion hepatitis C acquired at different ages and detected in look-back screening

Objectives: The prevalence of hepatitis C virus (HCV) infection in Sweden is estimated to 0.5%. Before 1992, blood transfusion posed a risk of HCV transmission. The primary aim of this study was to estimate anti-HCV prevalence in Stockholm County among individuals receiving blood transfusions 1965–1991. The secondary aim was to study the effect of age at transfusion on the development of liver disease and treatment outcome.

Materials and methods: This is a retrospective analysis of individuals found to be anti-HCV tested positive in Stockholm County during a national screening campaign in Sweden 2008–2010. All anti-HCV-positive individuals were also HCV RNA tested. Data on age at transfusion, age at diagnosis, HCV genotype, viral load, fibrosis score, liver histology and antiviral treatment were recorded.

Results: Out of 7473, 134 (1.8%) tested individuals were anti-HCV positive and 102 were HCV RNA positive resulting in a prevalence of chronic hepatitis C (CHC) of 1.4%. The rate of advanced liver damage was 18% (10/56). Patients younger than 19 years of age at transfusion were significantly more often started on antiviral treatment compared to adult patients, 65% vs 29% p?Conclusions: In this study, we found an anti-HCV prevalence of 1.8% which is considerably higher than the estimated prevalence in the Swedish general population (0.5%), and patients infected during childhood were more likely to receive antiviral treatment. Additional data on the HCV epidemic in Sweden are needed regarding prevalence and age distribution.     

Histological progression during short-term follow-up of patients with chronic hepatitis C virus infection

Assessment of prognosis from hepatitis requires liver histology. When the fibrosis stage is known, and if the fibrosis progression rate can be established, time to development of cirrhosis can be calculated. The fibrosis progression rate can be calculated from a single biopsy when duration of infection prior to biopsy is known. Sequential biopsies can also be examined. In this work, we studied histological activity and fibrosis stage in liver biopsies of 157 hepatitis C virus (HCV)-infected patients, including 92 for whom the approximate duration of infection was known. The mean fibrosis progression rate was 0.09 units per year, and was not influenced by mode of infection or viral genotype. Forty-six patients who had very mild histological changes in the initial biopsy underwent repeat biopsy 2 years later (with no intervening anti-viral treatment). Comparison of paired biopsies confirmed a tendency to histological progression and increasing hepatic fibrosis (mean, 0.15 fibrosis units per year). A normal baseline alanine aminotransferase (ALT) value was associated with slow fibrosis progression before baseline biopsy and between biopsies. These data do not differ from published cross-sectional and longitudinal studies, and suggest that histological progression will be observed during follow-up of most patients, including those with mild histological changes at time of initial assessment.     

Chronic hepatitis C in children--review of natural history at a National Centre

The natural history of hepatitis C virus (HCV) infection in adults has been established, but less is known about outcome in children. We conducted a retrospective review of patients referred to Birmingham Children's Hospital Liver Unit, from 1991 till 2008, with the diagnosis of HCV was undertaken. Only children with documented positive HCV RNA and a minimum duration of follow-up of 6 months were included. One hundred and thirty-three children were identified. The route of transmission was transfusion acquired in 47%, vertically acquired in 49% and transplantation in 2%. Since 2000, most children were infected vertically. The overall rate of spontaneous viral clearance was 17.5% with higher clearance (27%) in the transfusion group compared to the vertically acquired group (9%). Seventy-six had a liver biopsy at diagnosis. There was no evidence of fibrosis in 46%, mild fibrosis in 50% and moderate to severe fibrosis in 4%. None had cirrhosis. There was a statistically significant relationship between fibrosis score and older age at the time of biopsy (P = 0.02) and longer duration of infection (P = 0.05). Eighty children received treatment for HCV. Sustained viral response (SVR) was influenced by viral genotypes, with significantly increased response rates in genotypes (G) 2 and 3 compared to G 1 and 4. Vertical infection is now the major route of HCV infection in children in the UK. Histological changes were mild at diagnosis, but the severity of fibrosis progressed with age. Consideration should be given to improve detection and diagnosis to refer children to specialist centres for management and antiviral therapy before developing fibrosis.     

Hepatitis C virus genotypes in chronic hepatitis C of children

SUMMARY. Several hepatitis C virus (HCV) genotypes have been recently identified and genotype 1b has been correlated with severe liver disease and a poor response to interferon therapy. HCV infection in children is an interesting model for evaluation of the relationship between HCV genotypes and liver disease, because of its relatively short duration and the infrequent association with confounding cofactors. We have investigated HCV genotypes, using a dot-blot hybridization assay with genotype-specific probes, in 36 Italian children with chronic hepatitis C who were otherwise well and had no other underlying disease. Only four patients were symptomatic; liver histology, obtained in 3 3 patients, showed minimal hepatitis in 17 and mild chronic hepatitis in 16. Infection with HCV genotype Ib was found in 55.5% of patients, with a peak prevalence of 83% in children from southern Italy (P < 0.05 vs other regions). The remaining children were infected with HCV genotype la (16.6%), genotype 2 (11.1%). and mixed (10.9%) or undetermined (2.7%) genotypes. In one patient, HCV viraemia was never detected. There was no statistically significant correlation between genotype and age, sex, source of infection, alanine aminotransferase pattern and histological activity index. These results indicate that genotype 1b is widespread among Italian children with chronic hepatitis C, although with significant geographical variations. It is not associated with a more severe liver disease, therefore suggesting that the greater severity of liver disease recently reported in adults could reflect the cumulative effects of disease duration and of interfering cofactors.     

Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort

Pegylated interferon therapy is highly effective in recently acquired HCV. The optimal timing of treatment, regimen and influence of host factors remains unclear. We aimed to measure sustained virological response (SVR) during recent HCV infection and identify predictors of response. Data were from five prospective cohorts of high‐risk individuals in Australia, Canada, Germany and the United States. Individuals with acute or early chronic HCV who commenced pegylated interferon therapy were included. The main outcome was SVR, and predictors were assessed using logistic regression. Among 516 with documented recent HCV infection, 237 were treated (pegylated interferon n = 161; pegylated interferon/ribavirin n = 76) (30% female, median age 35 years, 56% ever injected drugs, median duration of infection 6.2 months). Sixteen per cent (n = 38) were HIV/HCV co‐infected. SVR among those with HCV mono‐infection was 64% by intention to treat; SVR was 68% among HCV/HIV co‐infection. Independent predictors of SVR in HCV mono‐infection were duration of HCV infection (the odds of SVR declined by 8% per month of infection, aOR 0.92, 95% CI 0.85–0.99, P = 0.033), IFNL4 genotype (adjusted OR 2.27, 95% CI 1.13–4.56, P = 0.021), baseline HCV RNA <400 000 IU/mL (aOR 2.06, 95% CI 1.03–4.12, P = 0.041) and age ≥40 years (vs <30: aOR 2.92, 95% CI 1.31–6.49, P = 0.009), with no difference by drug regimen, HCV genotype, symptomatic infection or gender. The effect of infection duration on odds of SVR was greater among genotype‐1 infection. Interferon‐based HCV treatment is highly effective in recent HCV infection. Duration of infection, IFNL4 genotype and baseline HCV RNA levels can predict virological response and may inform clinical decision‐making.     

Hepatitis C virus infection in multi-transfused children with haematological malignancy

Summary. Transmission of hepatitis C virus (HCV) is an important hazard of blood transfusion and may result in chronic liver disease. 98 children from Nottingham and Sheffield with haematological malignancies were studied to determine the prevalence of HCV infection by enzyme immunoassay and RT/PCR techniques. The children had been exposed to up to 184 donors through red cell and platelet transfusion, the majority prior to routine testing for HCV infection in blood donors. Only one sample showed evidence of HCV infection being both FXISA and RT/PCR positive. None of the samples taken since donor screening were positive. This provides reassurance as to the low rate of HCV acquisition in multi-transfused patients in this part of the U.K. compared to other parts of the world.     

Prognosis of hepatitis C virus-infected Canadian post-transfusion compensation claimant cohort

Summary.  Accurate prognostic estimates were required to ensure the sufficiency of the $1.1 billion compensation fund established in 1998 to compensate Canadians who acquired hepatitis C virus (HCV) infection through blood transfusion between 1986 and 1990. This article reports the application of Markov modelling and epidemiological methods to estimate the prognosis of individuals who have claimed compensation. Clinical characteristics of the claimant cohort ( n  = 5004) were used to define the starting distribution. Annual stage-specific transition probabilities (F0→F1, . . ., F3→F4) were derived from the claimants, using the Markov maximum likelihood estimation method. HCV treatment efficacy was derived from the literature and practice patterns were estimated from a national survey. The estimated stage-specific transition probabilities of the cohort between F0→F1, F1→F2, F2→F3 and F3→F4 were 0.032, 0.137, 0.150 and 0.097 respectively. At 20 years after the index transfusion, approximately 10% of all living claimants ( n  = 3773) had cirrhosis and 0.5% developed hepatocellular carcinoma (HCC). For nonhaemophilic patients, the predicted 20-year (2030) risk of HCV-related cirrhosis was 23%, and the risk of HCC and liver-related death was 7% and 11% respectively. Haemophilic patients who are younger and are frequently co-infected with human immunodeficiency virus would have higher 20-year risks of cirrhosis (37%), HCC (12%) and liver-related death (19%). Our results indicate that rates of progression to advanced liver disease in post-transfusion cohorts may be lower than previously reported. The Canadian post-transfusion cohort offers new and relevant prognostic information for post-transfusion HCV patients in Canada and is an invaluable resource to study the natural history and resource utilization of HCV-infected individuals in future studies.     

Long-term follow-up of non-A, non-B (type C) post-transfusion hepatitis

One hundred and thirty-five patients who developed non-A, non-B post-transfusion hepatitis mostly after cardiac surgery, were followed for a mean (±S.D.) of 90±41 months (range: 13–180) to evaluate clinical and histological outcome.Thirty-one cases resolved within 12 months, while 104 (77%) progressed to chronicity. Twenty-one of 65 (32%) biopsied patients developed cirrhosis at the end of the follow-up, and one further progressed to hepatocellular carcinoma. One patient had a complete histological remission (1%). The remaining cases had chronic active (37%), chronic persistent (27%) or chronic lobular hepatitis (3%). About half of the cases with cirrhosis developed portal hypertension, and three of these died due to esophageal varices hemorrhage, one due to liver failure, and one due to hepatocellular carcinoma. Out of 26 patients with the initial histologic diagnosis of chronic hepatitis that were rebiopsied during follow-up, 13 (50%) progressed to cirrhosis. These patients were significantly older than patients who did not develop cirrhosis (mean age 57 and 45 years respectively; p<0.01).During acute hepatitis anti-HCV was positive in all but one of the 114 patients tested. Percentages were similar for patients who recovered (95%) and those who developed chronic hepatitis (100%). However, during follow-up, 71% of the 1st generation and 21% of the 2nd generation ELISA test patients with acute resolved hepatitis became anti-HCV negative, while the same figures in chronic cases were only 8.5% (p<0.0001) and 1.4% (p=0.012). This suggests a correlation between anti-HCV antibody activity, hepatitis C virus replication, and the development of chronic liver disease.     

Clinical and serological courses of a newborn with post-transfusion hepatitis C

Summary. The clinical and serological course of a haemophilic baby who was transfused with 160 ml of blood containing the hepatitis C virus (HCV) (0.70 Meq. ml^-1) on the sixth post-natal day is described. He is the infant of an HCV-negative mother. One month after the transfusion, there was a marked increase in HCV RNA and a small amount of HCV antibody was detected. This case provides evidence that a newborn is capable of producing HCV antibodies.     

The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection

BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.     

Effect of hepatitis C antibody screening in blood donors on post-transfusion hepatitis in Taiwan

A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second-generation immunoassay. To study the impact of this screening on post-transfusion hepatitis in Taiwan, a prospective study on post-transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow-up period for more than 6 months post-transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that the current anti-HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.     

Epidemiological survey of Japanese children infected with hepatitis B and C viruses

Aim: The lack of a nationwide survey on hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Japan led us to investigate the epidemiological profiles of these infections among Japanese children. Methods: We conducted a questionnaire survey of children (<20 years of age) infected with either HBV (n = 136) or HCV (n = 114), who visited 636 pediatric institutions in Japan from 2003 through 2005. Most HBV‐infected subjects (94%) were born in 1986 or after when a nationwide immunization program for infants born to HBe antigen‐positive carriers was initiated. The transmission routes were divided into five groups: maternal, horizontal (subdivided into intrafamilial, iatrogenic and other horizontal), and unknown transmission. Results: Comparison of subjects born in 1990 or after and those born in 1989 or before, when anti‐HBc and anti‐HCV (c100‐3) screening tests of blood donors began, showed a shift in the relative proportions of maternal, intrafamilial, iatrogenic, other horizontal, and unknown transmission from 52%, 19%, 4%, 7% and 19% to 70%, 14%, 6%, 1% and 9%, respectively, for HBV, which was statistically insignificant (P = 0.120), and from 14%, 0%, 76%, 4% and 7% to 89%, 2%, 4%, 0% and 5%, respectively, for HCV, which was statistically significant (P < 0.001). HBV horizontal transmission did not decrease in proportion. No transfusion‐acquired HCV infection was reported in subjects born in 1993 or after. Conclusion: Maternal transmission is a prominent source of HCV infection among Japanese children. The implementation of measures to prevent HBV horizontal infection is also essential, and the present system of selective vaccination should be expanded to universal vaccination.     

Surveillance for newly acquired hepatitis C in Australia

BACKGROUND: The purpose of the present paper was to determine recent patterns of hepatitis C virus (HCV) transmission in Australia through a national system of enhanced surveillance of newly acquired hepatitis C. METHODS: Demographic, clinical, and risk behavior information on newly acquired hepatitis C cases from 1997 to 2000 was collected. Newly acquired hepatitis C included cases of HCV antibody sero-conversion within a 12 month period and acute clinical hepatitis C cases. RESULTS: Nine hundred and twelve cases of newly acquired hepatitis C were identified, representing 2.8% of all HCV notifications for this period. The majority of cases (72%) were diagnosed in people aged between 20 and 39 years. Injecting drug use was reported in the vast majority of cases (93%), with sexual transmission (2%) and tattooing (2%) reported in small numbers. HCV antibody sero-conversion was the mode of diagnosis in most cases (78%). CONCLUSIONS: Injecting drug use is the main route of HCV transmission in Australia. As only a small proportion of HCV infections are detected as newly acquired, enhanced surveillance procedures, including increased regular HCV testing of at-risk populations are required to more effectively monitor recent patterns of transmission.     

Low prevalence of hepatitis C virus infection in patients with auto-immune hepatitis type 1

Hepatitis C virus (HCV) antibodies were measured in 28 patients with auto-immune hepatitis type 1 using six different assay kits, three for C100–3 antibody and three for second generation HCV antibody, and two confirmatory tests to determine the prevalence of HCV infection in auto-immune hepatitis. These patients were confirmed to have human leucocyte antigen DR 4 or 2 which is susceptible to auto-immune hepatitis in Japanese. Of the 28 patients, four (14.3%) were positive for HCV antibody in all assays and reacted positively in at least one of the two confirmatory tests, indicating a true positive finding. Eight were positive for HCV antibody only by the Ortho ELISA kit and were negative in both confirmatory tests. The cut-off level for these results was low and became negative soon after the patients received corticosteroid treatment. Thus, these eight patients are presumed to be false-positive reactors. Hepatitis C virus RNA was detected in the serum of two of the four patients with HCV antibody and in none of 24 patients without HCV antibody. No significant difference was observed between the patients with and without HCV antibody in terms of clinical background, liver function tests and auto-antibodies. Our results showed that the prevalence of a past or present HCV infection in patients with auto-immune hepatitis in Japan is low; thus, auto-immune hepatitis is thought to be distinct from hepatitis type C. However, it is also suggested that HCV infection can potentially trigger auto-immune hepatitis.     

Prevalence of hepatitis C virus infection in thalassemia and haemodialysis patients in north Iran-Rasht

Hepatitis C virus (HCV) seroprevalence and risk factors in north Iran were investigated in 105 thalassemia sufferers, 93 haemodialysis patients and 5976 blood donors by second generation ELISA. Our study showed that haemodialysis patients and thalassemia sufferers were at higher risk of having HCV infection; the prevalence being 55.9% and 63.8% respectively in comparison to the prevalence of blood donors (0.5%). A confirmatory immunoblotting was employed using HCV-positive cases (54 thalassemia sufferers and 19 blood donors). The result showed that 92.6% of samples of the first group and 10.5% of the latter were positive. Thus, it can be suggested that ELISA in low-risk cases may produce considerable false positives. In HCV-positive patients with thalassemia, the incidence of HCV among different age groups and genders was similar but a strong correlation in respect to the number of blood transfusion (P=0.008) was observed. In HCV-positive haemodialysis patients, it was found that there was no correlation with liver function tests (alanine aminotransferase and aspartate aminotransferase: ALT and AST), but a significant correlation was observed in respect to the duration of dialysis(P=0.000) and the number of units transfused (P=0.000). Consequently, it still seems blood transfusion is the main factor for increasing the incidence of HCV in thalassemia sufferers and haemodialysis patients.     

Human immunodeficiency virus infection and hepatitis C pathology

ABSTRACT: To investigate the possible influence of human immunodeficiency virus (HIV) infection on hepatitis C virus-related liver disease, liver morphology was evaluated in 160 HBsAg-negative patients with chronic hepatitis C, including 68 HIV-positive and 92 HIV-negative cases. No differences were detected in the severity of necro-inflammatory hepatic lesions between HIV-negative and HIV-positive patients when the CD4+ lymphocytes count exceeded 400 cells/mm³. In contrast, HIV-positive patients with CD4+ lymphocytes below 400/mm³ showed a significantly lower grade of portal inflammation and piecemeal necrosis. These results suggest that liver lesions in hepatitis C may largely depend on immunomediated mechanisms.     

Hepatitis C virus infection in patients with leukemia

We have studied 30 patients with acute leukemia by the second-generation assay for antibodies to hepatitis C virus (HCV) to determine the incidence of HCV infection and the impact of anti-HCV positivity on liver disease. After a complete remission, 21/30 (70%) patients were anti-HCV-positive. During chemotherapy the anti-HCV-positive patients had more severe liver disease than the anti-HCV-negative patients, and they had a higher incidence of chronic hepatitis (13/21; 62% vs. 1/9; 11%, P < 0.01). During subsequent follow-up, 15/30 (50%) patients relapsed and 15/30 (50%) patients completed the chemotherapy protocols. After a relapse 12/15 (80%) patients were anti-HCV-positive and they had more severe liver disease than the anti-HCV-negative patients. Among the patients who completed chemotherapy (n = 15), biochemical evidence of chronic hepatitis was found in 9/9 (100%) anti-HCV-positive, and 2/6 (33%) anti-HCV-negative cases during off-therapy follow-up after therapy-withdrawal (P < 0.05). These results indicate that HCV plays an important role in the etiology of chronic hepatitis which could worsen the final prognosis of successfully treated patients with leukemia. © 1994 Wiley-Liss, Inc.