Therapy of hepatitis C: alpha interferon and ribavirin

Ribavirin is a nucleoside analogue that has been evaluated as a therapy of chronic hepatitis C alone and in combination with alpha interferon. Ribavirin is well absorbed orally and is typically given in doses of 1,000 to 1,200 mg/d. Three randomized, placebo-controlled studies comprising more than 150 patients have shown that therapy with ribavirin alone for 24 to 48 weeks resulted in a significant reduction in serum alanine aminotransferase (ALT) levels during therapy. However, ribavirin therapy did not lead to a substantial reduction in hepatitis C virus (HCV) RNA levels; almost all patients remained viremic, and serum aminotransferase levels increased to pretreatment values when therapy was stopped. The most common adverse event was a moderate and reversible hemolysis during treatment that caused a decrease in hemoglobin by 10% to 20% of baseline levels. Combination therapy of ribavirin with alpha interferon has demonstrated promise both in pilot studies and a recently completed randomized controlled trial. Ribavirin in standard doses combined with alpha interferon in doses of 3 million units (MU) three times weekly for 6 months was found to significantly improve the sustained biochemical and virological response rates compared with interferon alone. Combination therapy offers a promise to become standard therapy for patients with nonsustained response to alpha interferon alone, because the majority of such patients achieve a durable response after treatment with combination therapy. However, nonresponders to alpha interferon alone rarely achieve a sustained beneficial response to combination treatment. For interferon-naive patients, combination therapy is superior to therapy with alpha interferon alone in achieving sustained biochemical and virological responses, but the combination demonstrates clear-cut superiority only in patients with unfavorable profiles for a response to interferon, in particular patients with high levels of HCV RNA. The optimal use and regimen of combination therapy awaits further investigation. New antiviral agents are still needed for the proportion of patients who do not respond to alpha interferon, even in combination with ribavirin.