Comparative effects of different doses of ribavirin plus interferon-alpha(2b) for therapy of chronic hepatitis C - Results of a controlled, randomized trial

Compared to either drug alone, therapy with the combination of ribavirin an d interferon-a leads to improved rates of response in patients with chronic hepatitis C. Side effects often mandate downward dose adjustment or cessat ion of therapy, and the optimal dose of ribavirin has not been established. The aim of this study was to learn whether 600 mg ribavirin per day would prove as efficacious as 1000-1200 mg/day when combined with interferon (3 m illion units thrice weekly) for therapy of patients previously treated with standard interferon who had failed to respond or who had relapsed. We enro lled 69 patients with chronic hepatitis C and compensated liver disease: 45 were men, 65 were Caucasian, 48 were infected with genotype 1 hepatitis C virus. By random assignment, 35 received 600 mg ribavirin/day (group A), wh ereas the other 34 received 1000 mg (less than or equal to 75 kg body wt) o r 1200 mg/day (> 75 kg body wt) (group B). At baseline, the two groups were well matched for demographic and laboratory features. In both groups, mean serum levels of alanine aminotransferase (ALT) and hepatitis C viral (HCV) RNA levels fell promptly and remained significantly lower than baseline th roughout 24 weeks of therapy. There was no significant difference in mean l evels of ALT or HCV RNA during therapy or at the end of follow-up (24 weeks after cessation of therapy). At the end of 24 weeks of posttherapy follow- up, 12 patients in each group had undetectable HCV RNA in serum, whereas 11 (31%) in group A and 9 (26.5%) in group B had normal serum ALT levels. The lower doses of ribavirin (group A) were tolerated better. In conclusion, in previous nonresponders or relapsers to interferon done, c ombination therapy with interferon-alpha (2b) (3 MU thrice weekly) + 600 mg ribavirin/day is tolerated better and is as effective as interferon plus h igher (standard) doses of ribavirin (1000-1200 mg/day).