INTRON A VS INTRON A PLUS RIBAVIRIN FOR TREATMENT OF CHRONIC HEPATITIS C

Northwestern University, Evanston IL

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Abstract

Hepatitis C virus (HCV) is the major etiologic agent of post-transfusion, non-A, non-B hepatitis and is an important worldwide health problem. Since HCV results in chronic infection in as many as 90% of infected individuals of which up to 50% develop cirrhosis (with its complications portal hypertension, ascites, encephalopathy, and bleeding disorders), the seriousness of the disease is apparent. In addition, chronic HCV infection can lead to highly lethal hepatocellular carcinoma. The only approved therapy of chronic HCV infection is interferon alpha (3 million units three times weekly). 50% of patients respond to this medication with normalization of serum liver enzymes (ALT) but only 10-20% continue to show benefit one year after starting therapy. Unfortunately, the majority of patients will either not respond to interferon alpha or will relapse after an initial response to the medication (reappearance of the virus in their serum and recurrence of abnormal serum aminotransferases). Hence, methods to enhance the efficacy of interferon alpha have been sought. There is evidence that higher initial doses of interferon alpha may result in a greater antiviral effect and increase sustained response rate to interferon alpha. High initial doses of interferon alpha followed by maintenance dosage at the standard dosage results in higher viral clearance and such regimens are now being investigated in combination with ribavirin in patients who have failed or relapsed after previous interferon alpha therapy. Furthermore, the anti-viral medication ribavirin has drawn interest as an anti-vrial agent for HCV since it has known antiviral activity against RNA viruses. It has been used as monotherapy in chronic HCV and has resulted in decreased serum aminotransferases. However, serum viral levels have not decreased and the beneficial effects regarding lowered serum aminotransferases have reversed upon discontinuation of ribavirin. Ribavirin has also been used as an adjunct to interferon alpha. In patients who have not previously been treated with interferon alpha, there is an increase in the sustained response rate as compared with standard interferon alpha monotherapy. Ribavirin is administered orally and has associated with its use hemolytic anemia. This is usually mild and well-tolerated and reverses with discontinuation of the drug. However, the anemia can be more pronounced and regular montiroing of hemoglobin is required. Combination therapy with interferon alpha and ribavirin is currently the subject of extensive research in the United States in patients with chronic HCV infection.