Efficacy of a short-term ribavirin plus interferon alpha combination therapy followed by interferon alpha alone in previously untreated patients withchronic hepatitis C: a randomized multicenter trial

Background. Combination therapy with interferon alpha (IFN alpha) plus riba virin has been shown to improve the sustained response rate in patients wit h chronic hepatitis C but there is little information regarding the lengths of time for this therapeutic regimen. In this study we therefore tried to evaluate whether the analysis of different virological parameters could pro vide new clues with respect to the early determination of the efficacy of t his form of combination therapy. Furthermore, we also examined whether shor t-term induction combination therapy followed by IFN alpha alone is more ef fective than monotherapy in mounting an initial as well as a sustained viro logical response. Methods: 185 patients with histologically proven chronic hepatitis C (mean age 42 years (range 19-65 years); 110 males, 75 females) were enrolled in the study. The patients were randomly assigned to receive, over the first 12 weeks, either interferon alpha 2a 6 million units (MU) t hree times weekly plus ribavirin 14 mg/kg per day (n=93) or the same dose o f IFN alpha alone (n=92). Patients with a virological response (serum HCV R NA undetectable) after 12 weeks were subsequently treated with 3 MU IFN alp ha alone thrice weekly for a further 40 weeks. Otherwise, treatment was dis continued. After the end of treatment, patients were followed up for 24 wee ks. Results: Patient characteristics at baseline were not significantly dif ferent in the two treatment groups. An initial virological response at week 12 was seen in 61 (66%) patients receiving IFN alpha plus ribavirin and in 44 (48%) being treated with IFN alpha alone (p=0.015) and this improvement in the response rate was mainly restricted to HCV genotype 1-infected pati ents (58% vs, 38%), In contrast, end-of-treatment (week 52) and sustained v irological response rates were similar in both groups (37% vs. 29% and 26% vs. 17% [p = 0.1], respectively). Interestingly, patients with HCV genotype 3, however, clearly benefited from short-term combination therapy. Thus, s ustained virological response rates in these patients significantly increas ed from 25% (IFN alpha monotherapy) to 59% (combination therapy) (p=0.05). Conclusions. Short-term combined therapy for 12 weeks is more effective tha n the monotherapy with respect to the induction of an initial virological r esponse but this effect applies only to genotype 1-infected patients. Howev er, there is no significant difference between both therapeutic schedules w ith regard to the induction of sustained response. Although HCV genotype 3- infected patients seem to benefit from this short-term combined therapy, pr olonged combined therapy may be necessary in HCV genotype 1-infected patien ts.