Principles of interferon induction therapy

Abstract

Several strategies have been devised to enhance the number of patients with hepatitis C virus (HCV) infection who achieve a sustained response to interferon-α therapy. Induction therapy uses higher than usual doses of interferon, given on a daily, rather than three times per week basis, for a defined period. The goal is to minimize fluctuations in interferon levels, preventing viral rebound in periods when drug levels are low. The optimal interferon-α-2b dose for acute viral clearance is probably 10 MIU. Studies of HCV viral kinetics after interferon-α dosing have shown a biphasic response to drug. In the initial 24 to 48 hours after a dose of interferon, there is an extremely rapid, interferon-dose–dependent decrease in viral titer. This reflects inhibition of viral production and/or release. The second lower phase of viral decrease then ensues, which is highly variable between patients. It is thought to reflect the death rate of infected hepatocytes. Brisk decrease during the second phase of viral kinetics is the best predictor of HCV-RNA clearance by 3 months. Second-phase viral decrease correlates with histologic activity on liver biopsy and pretreatment serum transaminase levels. Hepatitis C virus genotype differences are important, as well, because genotypes 2 and 3 are cleared by interferon more readily than the more resistant genotype 1.