Antiviral therapy for chronic hepatitis C: past, present, and future.

Antiviral therapy for chronic hepatitis C has dramatically advanced since the discovery of the hepatitis C virus (HCV) in 1989 and the introduction of interferon (IFN) monotherapy in the early 1990s. The current standard therapy uses a combination of pegylated IFN and ribavirin. The duration of therapy and response to therapy are HCV genotype-specific. Genotype 1 patients require 48 weeks of the combination therapy for 50% successful viral elimination, while genotype 2 patients require 24 weeks of therapy for 80% or 90% viral elimination. Early viral kinetics after the initiation of therapy is a useful predictor of the sustained virologic response (SVR), which is formally determined at 24 weeks after completion of the treatment. For example, an early virologic response, which is determined by a 2-log reduction of HCV RNA or viral elimination at 12 weeks after the initiation of therapy, is a strong negative predictor of SVR in genotype 1 patients. In contrast, a rapid virologic response of HCV RNA-negative at 4 weeks after the initiation of therapy identifies genotype 2 "super-responders," who may require a shorter period of therapy. Adherence to therapy is one of the most important factors for successful viral clearance. Hematopoietic growth factors such as epoetin and granulocyte-colony stimulating factor help reduce therapy-mediated cytopenia and improve patient compliance, thereby leading to better viral clearance. New types of anti-HCV agents such as HCV protease and polymerase inhibitors are needed for those patients that do not respond to combination therapy.