Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C - Meta-analysis of individual patient data from European centers

Background/Aims: This study aimed to obtain a more precise estimation of the efficacy and tolerability of interferon-ribavirin combination therapy for chronic hepatitis C. Methods: A meta-analysis was carried out of individual patient data comprising about 90% of the published experience with combination therapy, The study was set in four European university-affiliate liver referral centers, A total of 186 individuals with chronic hepatitis C who had participated in three randomized controlled trials and one open study were selected for the study, Fifty-one had received ribavirin monotherapy (1000-1200 mg/day), 37 interferon monotherapy (3 MU 3 x /week) and 78 interferon-ribavirin combination therapy (dosage as for monotherapy) for 6 months, Twenty patients served as controls, Follow-up after therapy was 6 months. Data analysis was by the multivariate logistical regression method. Results: The primary outcome measure for efficacy was the percentage with a sustained response (ALT normalization and HCV RNA negativity 6 months after therapy), The sustained response rate was significantly higher for interferon-ribavirin combination therapy than for interferon or ribavirin monotherapy (odds ratio IFN-Riba vs IFN = 9.8, 95% CI 1.9-50), The estimated probability of sustained response following interferon-ribavirin combination therapy was 51% for patients without previous IFN therapy, 52% for patients with previous IFN therapy and response-relapse, and 16% for previous IFN non-responders. No serious adverse events were observed and less than 10% withdrew. Conclusions: The efficacy of interferon-ribavirin therapy appears to be enhanced two- to threefold over interferon monotherapy in all major subgroups of chronic hepatitis C patients tested. In view of its acceptable toxicity profile, interferon-ribavirin combination therapy is a candidate for the new standard therapy for chronic hepatitis C.