Pegylated interferon plus ribavirin for the treatment of chronic hepatitis C

Abstract

Peginterferon alfa-2a and peginterferon alfa-2b have been approved for the treatment of chronic hepatitis C virus (HCV) infection in adults who have compensated liver disease and have not been previously treated with interferon alfa. Peginterferon alfa-2a and peginterferon alfa-2b have also been approved for use in combination with ribavirin as therapy for these adults. Combining peginterferon alfa-2a or alfa-2b with ribavirin produces better activity against HCV than either drug alone. Interferon works by binding to specific receptors on the cell surface that initiate a complex cascade of protein-protein interactions leading to rapid activation of gene transcription. The effects of this interferon-stimulated gene modulation depend on the biologic system and may result in the inhibition of viral replication in infected cells, inhibition of cell proliferation, and immunomodulation. Pegylation of the interferon molecule increases its size; the absorption of the larger pegylated molecule is slower, its half-life is longer, and its rate of clearance from the plasma is lower than that of the native interferon. Thus, the pegylated molecule increases the duration of biologic activity. Factors that appear to influence the success of pegylated interferon therapy are HCV genotype, baseline viral load, presence of fibrosis or inflammation shown on the liver biopsy at baseline, and the patient's body weight or body surface area. Patients infected with HCV genotype 1 tend to have a lower response rate, require longer courses of therapy, and respond better when treated with a pegylated interferon plus ribavirin. Patients infected with HCV genotypes 2 or 3 have comparable responses when treated with interferon plus ribavirin or pegylated interferon plus ribavirin and can be treated with a lower dose of ribavirin and a shorter course of therapy (24 weeks vs 48 weeks for patients with genotype 1). Studies directly comparing peginterferon alfa-2a and peginterferon alfa-2b have not been performed.