Mechanisms of drug resistance and novel approaches to therapy for chronic hepatitis C

Abstract

Hepatitis C virus (HCV) is now the major cause of transfusion-associated and parenterally transmitted viral hepatitis and accounts for a significant proportion of hepatitis cases worldwide. The majority of infections become persistent and approximately 20% of chronically infected individuals develop cirrhosis, which is strongly associated with progression to hepatocellular carcinoma. Molecular biological investigations into the structure and function of HCV and its genes has led to the identification of a number of potential targets for selective antiviral intervention. The present review summarizes current research activity into these novel drug targets and addresses the basis for clinical non-response in the current interferon-alpha-based therapies. Future therapeutic strategies that utilize HCV-specific antiviral agents should prove effective in controlling active viral replication, but the risk of emergence of drug-resistance will need to be addressed due to the quasispecies feature of HCV replication.