Hepatitis C

The major cause of chronic post-transfusion hepatitis, the hepatitis C virus (HCV), has been identified. HCV is a single-stranded linear RNA virus with characteristics similar to the flaviviruses. A different agent, the hepatitis E virus, is associated with epidemic (enterically-transmitted) non-A, non-B hepatitis. At present, infection with HCV is recognized by the finding of anti-HCV antibodies, positive in up to 90% of patients with chronic non-A, non-B post-transfusion hepatitis. Antibodies to HCV are detected in 1% of normal volunteer blood donors and in the majority of donors implicated in post-transfusion hepatitis. HCV antibodies are also found in patients with autoimmune liver disease and hepatocellular carcinoma. Moreover, HCV infection may contribute to the pathogenesis of liver disease in alcoholic patients. The role of HCV infection in fulminant non-A, non-B hepatitis and hepatitis-associated aplastic anemia has not been elucidated as yet. Therapy of chronic non-A, non-B hepatitis with recombinant human alpha-interferon has been shown to improve or normalize aminotransferase levels in approximately 50% of patients, most of whom have evidence of HCV infection. However, relapse after cessation of treatment is common. In the future, screening blood for evidence of HCV infection may prevent most cases of non-A, non-B post-transfusion hepatitis.     

Hepatitis C

Opinion statement  

Hepatitis C

Hepatitis C virus commonly causes chronic liver disease. Chronicity as a result of the failure of T-cell-mediated immunity, liver damage caused by cytotoxic T lymphocytes, and the evolution of genetic diversity characterize hepatitis C infection. Progression, typically silent, is determined by sex, age, alcohol and immune status. Interferon and ribavirin are effective in the substantial minority of patients with less advanced fibrosis and lower hepatitis C viral loads.     

Persistent Hepatitis C viremia after acute self-limiting posttransfusion Hepatitis C

Persistent viremia after clinical or subclinical hepatitis C virus (HCV) infection is believed to occur in patients with chronic hepatitis C, but little is known about the duration of HCV replication in patients with acute hepatitis who have recovered or the relation of HCV viremia with the kinetics of antibodies to HCV (antiHCV). We tested HCV-RNA and anti-HCV in serial serum samples from 41 patients with posttransfusion non-A, non-B hepatitis, followed for an average of 6 years after transfusion. Serum HCV-RNA was measured by nested polymerase chain reaction, which used primers from the 5′ untranslated region of the HCV genome. Anti-HCV were tested with first- and second-generation enzyme-linked immunosorbent assays (ELISA 1 and ELISA 2), and with a second-generation recombinant immunoblot assay. Of the 41 patients, 10 recovered and 31 progressed to chronic liver disease. HCV-RNA was detected in serum before or simultaneously with the onset of hepatitis in all cases, and lasted between 2 and 6 weeks in 5 of the 10 patients who recovered, whereas it persisted for the entire follow-up period in every case with chronic hepatitis and in the remaining 5 patients with self-limiting hepatitis. Anti-HCV were detected with ELISA 2 in the first serum sample, with raised serum transaminases in 57% of patients, but in only 6% with ELISA 1. In the sample obtained 1 month after the onset of hepatitis, anti-HCV were detected with ELISA 2 in 94% of patients, but in 34% with the ELISA 1. Anti-HCV (anti C-33 and anti-c22) were cleared in the five patients with transient hepatitis C viremia, but remained detectable in those with chronic viremia. In conclusion, serum HCV-RNA is detected at the onset of acute posttransfusion hepatitis C and persists in patients progressing to chronic hepatitis. Some patients with self-limiting hepatitis become HCV-RNA negative soon after the onset of hepatitis, whereas in others it persists throughout follow-up, suggesting the development of a silent carrier state.     

Hepatitis C lookback

Hepatitis C was responsible for the majority of cases of posttransfusion hepatitis before the introduction of a specific screening test for blood donors. Infected recipients may remain asymptomatic for many years, but cirrhosis and hepatocellular carcinoma may develop decades after infection. Lookback, or the identification of recipients of potentially contaminated blood, is now being conducted in many countries, including Holland, Denmark, the United Kingdom, Canada, New Zealand, and the United States. In targeted lookback, recipients of blood from donors subsequently found to be positive for hepatitis C are notified and advised to undergo testing. In general lookback, all patients who received blood before being tested for hepatitis C are advised to undergo testing. Difficulties with both forms of lookback illustrate the importance of vein-to-vein tracking of blood products, including the potential utility of a centralized registry of blood product recipients.     

Hepatitis C virus

Identification and diagnosis of the infecting agent responsible for hepatitis C have only recently occurred. Recognition of an infecting agent distinct from that resulting in hepatitis A or B was made approximately 50 years ago. However, the ability to screen and detect this agent was possible only after molecular biology studies which led to the cloning of parts of the hepatitis C virus (HCV) and the development of a diagnostic antibody test reported by Michael Houghton and colleagues in 1989. The discovery and cloning of HCV has led to a greater understanding of its relationship to acute and chronic hepatitis, cirrhosis, primary liver cancer, and extrahepatic conditions including essential cryoglobulinemia, glomerulonephritis, and serum autoantibody positivity. New antibody tests and quantitation of HCV-RNA have allowed better diagnosis of infectivity and monitoring of treatment effects. HCV genotypes are being related to the natural history of the disease and the effects of treatment. Research continues on HCV hepatitis and other newly identified viral hepatitis agents.     

Hepatitis C.

Until recently the diagnosis of non-A, non-B hepatitis was made by excluding other detectable viral infections of the liver. Progress in molecular biology made it possible to develop assays which can trace antibodies against the hepatitis C virus. This virus plays a major role in the pathogenesis of transfusion-related and sporadic non-A, non-B hepatitis and possibly of other liver diseases. Although the genome of a few isolates of the hepatitis C virus has already been decoded, the viral particles have not yet been visualized.     

Hepatitis C Management in Patients with Hepatitis C and HIV Co-infection

Co-infection with HIV and hepatitis C (HCV) is common due to similar risk factors. Twenty-five to thirty percent of HIV+ patients are co-infected with HCV. HCV infection in HIV+ patients is associated with higher rates of fibrosis, progression to cirrhosis and decompensated liver disease, and liver-related mortality. The ultimate HCV treatment goal is viral eradication, or sustained virologic response (SVR) which results in decreased liver-related morbidity and mortality. Prior therapies were suboptimal in co-infected patients. However, the new HCV direct-acting antiviral agents provide excellent treatment options in co-infected patients with response rates and adverse events similar to the HCV mono-infected population. Drug interactions between HIV treatments and HCV treatments can be challenging and must be taken into consideration. To optimize outcomes, co-infected patients should be managed by experienced providers or in the setting of a collaborative multidisciplinary approach. This article will review the current treatment rationale and recommendations for HIV-HCV-co-infected patients.     

Hepatitis C and pulmonary fibrosis: Hepatitis C and pulmonary fibrosis

Background

Hepatitis C virus (HCV) is a hepatotropic and lymphotropic virus that causes hepatic and extrahepatic disease. Emerging clinical data suggest that chronic HCV infection can lead to many direct and indirect effects on the lung.

Objectives

This article discusses evidence on the relationship between HCV infection and pulmonary fibrosis to increase knowledge on this topic among clinicians and scientists and highlights the need for further study.

Methods

We searched the MEDLINE, ISI WEB OF KNOWLEDGE, OVID, ELSEVIER, and MDCONSULT databases and top respiratory journals, such as the American Journal of Respiratory and Critical Care, Chest, and Thorax for articles in English using the following keywords: hepatitis C, HCV infection, IPF, pulmonary fibrosis, and interstitial pneumonitis. We reviewed the reference lists of all identified studies.

Results

The evidence for a pathogenetic link between pulmonary fibrosis and HCV is: the higher frequency of HCV markers in IPF patients, an increase in lymphocyte and neutrophil numbers in bronchoalveolar lavage of chronic HCV infection patients, and the development of IPF in HCV-related chronic hepatitis that is treated with interferon. There is a discrepancy between studies on the frequency of HCV in IPF patients, which might be attributed to geographical differences of in the prevalence of HCV infection, selection bias in choosing the control group, and the HCV genome.

Conclusions

BAL studies in HCV infection are associated with increased counts of lymphocytes and neutrophils in BAL fluid. These studies show that HCV infection is associated with nonspecific pulmonary inflammatory reactions that are not compatible with IPF but that it can lead to pulmonary fibrosis. The other factor is interferon therapy. Interstitial pneumonia and sarcoidosis are well-documented complications of IFN therapy. More extensive cohort studies should be conducted to confirm an actual causal relationship between HCV infection and pulmonary fibrosis.     

Evolution of Hepatitis C Virus Quasispecies in Children with Chronic Hepatitis C

Abstract Background: Hepatitis C virus (HCV) circulates as a mixture of different but closely related genomes: this quasispecies nature could be essential for virus persistence and could induce resistance to interferon therapy. Since little is known on the behavior of HCV quasispecies in children and adolescents with chronic hepatitis C, we analyzed the virus population in six untreated children during a 5-year follow-up. Methods: Six children aged 1–8 years, infected early in life with HCV, were included in the study. From each of them, 2 or 3 sequential serum samples obtained over a 5-year follow-up period were examined. The HCV quasispecies heterogeneity and diversity in the E2 hypervariable region-1 (HVR-1) were analyzed among samples by the heteroduplex mobility assay, and the distance between variants was estimated by the heteroduplex mobility ratio (HMR). Results: The HCV population was initially highly homogeneous in all six children. During follow-up, diversification of HVR-1 leading to a more complex viral population occurred in all cases, and was particularly evident in the three older children (HMR: 0.82–0.54). Changes in the HVR-1 sequence occurred without relation to the profile of ALT and HCV-RNA levels. Conclusions: HCV quasispecies diversification is a common event during chronic hepatitis C in childhood. Host and environmental pressure could be major determinants. The increasing viral heterogeneity could impair the response to antiviral therapy, thus indicating a rationale for early antiviral treatment in children with chronic hepatitis C.