THERAPY OF HEPATITIS-C - ALPHA-INTERFERON AND RIBAVIRIN

Ribavirin is a nucleoside analogue that has been evaluated as a therap y of chronic hepatitis C alone and in combination with alpha interfero n, Ribavirin is well absorbed orally and is typically given in doses o f 1,000 to 1,200 mg/d, Three randomized, placebo-controlled studies co mprising 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, ribavi rin therapy did not lead to a substantial reduction in hepatitis C vir us (HCV) RNA levels; almost all patients remained viremic, and serum a minotransferase levels increased to pretreatment values when therapy w as stopped, The most common adverse ev ent was a moderate and reversib le hemolysis during treatment that caused a decrease in hemoglobin by 10% to 20% of baseline levels. Combination therapy of ribavirin with a lpha interferon has demonstrated promise both in pilot studies and a r ecently completed randomized controlled trial, Ribavirin in standard d oses combined with alpha interferon in doses of 3 million units (MU) t hree rimes weekly fur 6 months was found to significantly improve the sustained biochemical and virological response rates compared with int erferon alone, Combination therapy offers a promise to become standard therapy for patients with nonsustained response to alpha interferon a lone, because tile majority of such patients achieve a durable respons e 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 t herapy 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 p rofiles 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 f or the proportion of patients who do not respond to alpha interferon, even in combination with ribavirin.