Hepatitis C virus: current understanding and prospects for future therapies

Hepatitis C virus (HCV) is the leading cause of chronic liver disease world wide and the leading indication for liver transplantation. The hallmark of the disease is its propensity to evolve into chronicity, probably because v iral heterogeneity allows the virus to escape immune-mediated neutratizatio n. Treatment with interferon alpha (IFN-alpha) has been disappointing, but higher and more frequent doses, and combination therapies, including nucleo side analogs, might lead to improved suppression of HCV RNA levels. Molecul ar analysis of HCV before and during treatment has indicated that high vira l RNA levels and the presence of HCV genotype 1 are independent predictors of poor treatment outcome, New antiviral agents in development include inhi bitors of HCV replicative enzymes, such as protease, helicase and polymeras e, as well as several genetic approaches, such as ribozymes and antisense o ligonucleotides. 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.