A randomized 4-Arm multicenter study of interferon alfa-2b plus ribavirin in the treatment of patients with chronic hepatitis C not responding to interferon alone

To determine whether a higher dosage of interferon (IFN) associated with ri bavirin and/or prolonged time of administration may improve therapeutic eff icacy, we: conducted a 4-arm randomized trial on patients with chronic hepa titis C not responding to one or more previous treatment courses with IFN m onotherapy. Group 1 (n = 139) received 3 million units (MU) IFN-alpha 2b 3 times a week (t.i.w.) plus ribavirin 1,000 mg/d for 12 months; group 2 (n = 162) received 5 MU t.i.w. plus ribavirin for 12 months; group 3 (n = 142) received 3 MU t.i.w. plus ribavirin for 6 months; and group 4 (n = 151)rece ived 5 MU t.i.w. plus ribavirin for 6 months. The primary end point was hep atitis C virus (HCV)-RNA clearance at the end of 6-month follow-up. HCV-RNA Tvas negative in 15% of group 1, 23% of group 2, 11% of group 3, 16% of gr oup 4 (group 2 vs. group 3, P = .04). Among patients with genotypes 1 and 4 , sustained response tvas significantly higher in group 2 vs. group 3 (18% vs. 7%, P = .03; group 1 = 9%, group 4 = 12%, P = not significant [NS]). In patients with genotypes 2 and 3, sustained virologic response was not affe cted by the different regimens (group 1 = 32%, group 2 = 30%, group 3 = 30% , group 4 35%, P = NS). In conclusion, about 23% of nonresponders to IFN mo notherapy may achieve a sustained response if re treated by 5 MU t.i.w. IFN plus ribavirin 1,000 mg/d for 1 ye Ir. Patients with genotype 1 should rec eive a high dosage of IFN plus ribavirin for 12 months, whereas therapy for patients with genotype 2 or 3 should be less aggressive.