Hepatitis C virus: current understanding and prospects for future therapies

Abstract

Hepatitis C virus (HCV) is the leading cause of chronic liver disease worldwide and the leading indication for liver transplantation. The hallmark of the disease is its propensity to evolve into chronicity, probably because viral heterogeneity allows the virus to escape immune-mediated neutralization. Treatment with interferon alpha (IFN-alpha) has been disappointing, but higher and more frequent doses, and combination therapies, including nucleoside analogs, might lead to improved suppression of HCV RNA levels. Molecular analysis of HCV before and during treatment has indicated that high viral RNA levels and the presence of HCV genotype 1 are independent predictors of poor treatment outcome. New antiviral agents in development include inhibitors of HCV replicative enzymes, such as protease, helicase and polymerase, as well as several genetic approaches, such as ribozymes and antisense oligonucleotides. The main hindrance to drug development for hepatitis C is the lack of a small animal model or a productive tissue culture system for assessing drug action.