Therapy with recombinant human
interferon alpha remains pivotal to the treatment for
chronic hepatitis C virus
liver disease. Semi-synthetic
protein-
polymer conjugates of
interferon with
polyethylene glycol have also been recently developed. These conjugates protect the
protein from degradation; reduce the immunogenicity; and prolong exposure to
drug by a sustained absorption, restricted volume of distribution and sustained high serum concentration.
Therapy with pegylated
interferons is associated with significantly greater sustained virological response rates (SVR) compared to the non-pegylated formulation.
Ribavirin is a
guanosine analog with minimal
antiviral activity against HCV. It demonstrates significant clinical synergism when administered in combination with
interferon.
Amantadine blocks entry of influenza A virus into cells. Used in combination with
ribavirin and
interferon as triple
therapy, it may have some benefit compared to dual or monotherapy. Current treatment with pegylated
interferons combined with weight-based
ribavirin, provides the highest sustained virological response rates. In the absence of suitable animal models, HCV dynamic studies in man have been helpful in defining the mechanisms of action of
interferon in chronic HCV
liver disease. Novel therapeutic agents are being developed as the replication cycle of HCV is being understood. However, their safety and efficacy remain to be established and availability for clinical use is unlikely within the next 3 to 5 years. This review describes current
antiviral therapy in chronic HCV
liver disease, addresses the potential role of viral dynamics in elucidating the mechanisms of action of the drugs and discusses future potential
therapeutics agents.