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[Viral hepatitis C]
S Zeuzem1, W K Roth, G Herrmann
1Medizinische Klinik II, Johann Wolfgang Goethe-Universität Frankfurt a.M..
Insights
Hepatitis C virus (HCV) infection is a major cause of liver disease. While interferon-alpha shows some efficacy, its sustained response rate is low, and vaccine development is challenging due to viral genetic diversity.
Area of Science:
- Virology: Focus on the (+)stranded RNA hepatitis C virus (HCV).
- Immunology: Examination of immune-mediated cytotoxicity in HCV infection.
Context:
- Hepatitis C virus (HCV) identified as the primary cause of non-A, non-B hepatitis.
- Recent investigations into HCV's genomic structure, genotypes, and replication sites (hepatic and extrahepatic).
- HCV exhibits significant genetic heterogeneity and rapid mutation, forming quasispecies and neutralization escape mutants.
Purpose:
- To review fundamental, diagnostic, and clinical aspects of acute and chronic HCV infection.
- To discuss HCV's association with other diseases and complications like liver cirrhosis and hepatocellular carcinoma.
- To evaluate the efficacy and limitations of interferon-alpha therapy and discuss post-transplant HCV reinfection.
Summary:
- Interferon-alpha normalizes aminotransferases and reduces liver inflammation in approximately 50% of chronic hepatitis C patients, but sustained response rates are below 30% post-treatment.
- HCV reinfection is common after liver transplantation, though typically mild under immunosuppression.
- Screening has reduced post-transfusion hepatitis C, but community-acquired transmission requires further study.
Impact:
- Highlights challenges in achieving sustained virological response with current interferon-alpha treatments for chronic hepatitis C.
- Underscores the difficulty in developing an effective hepatitis C vaccine due to the virus's rapid mutation and genetic diversity.
- Emphasizes the need for continued research into HCV transmission and improved therapeutic strategies.
Abstract:
Soon after the isolation of the hepatitis C virus (HCV) genome in 1988 it became evident that HCV is the most important cause of non-A, non-B-hepatitis. In recent years the structure of this (+)-stranded RNA-virus, the different genotypes of HCV and the replication in hepatic and extrahepatic sites have been investigated. HCV has a remarkable degree of genetic heterogeneity, mutates rapidly, leading to the simultaneous coexistence of different genoms in the same individual (quasispecies) and most likely to the generation of neutralization escape mutants. The cytotoxicity of the hepatitis C virus appears to be mainly immune-mediated. This review article summarizes basic, diagnostic and clinical aspects of acute and chronic HCV-infection, association with other diseases and complications such as liver cirrhosis and hepatocellular carcinoma. Interferon-alpha has been shown useful in normalizing serum aminotransferases and decreasing liver inflammatory lesions in about half of the patients with chronic hepatitis C. However, relapses after the cessation of interferon-alpha are frequent, leading to a sustained response in less than 30% of treated patients. Several clinical and biochemical parameters for response to interferon-alpha have been proposed. In patients with orthotopic liver transplantation due to progressive chronic hepatitis C and decompensated liver cirrhosis, reinfection of the donor organ frequently occurs. However, in transplanted patients under immunosuppression the course of hepatitis C reinfection is usually mild. Due to screening programs of blood and blood products the incidence of posttransfusion-acquired hepatitis C has declined. However, further efforts in understanding the transmission of community-acquired hepatitis C are necessary. The development of a hepatitis C vaccine will be difficult due to the high degree of viral genetic heterogeneity.