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

• Published in: Journal of hepatology 1997-05, Vol.26 (5), p.961-966
• Main Authors: Schalm, Solko W., Hansen, Bettina E., Chemello, Liliana, Bellobuono, Antonio, Brouwer, Johannes T., Weiland, Ole, Cavalletto, Luisa, Schvarcz, Robert, Ideo, Gaetano, Alberti, Alfredo
• Format: Article
• Language: English
• Subjects: Adult; Alanine Transaminase - blood; Biological and medical sciences; Chronic Disease; Chronic hepatitis; Cirrhosis; Drug Synergism; Drug Therapy, Combination; Female; Hemoglobins - analysis; Hepacivirus - genetics; Hepatitis C; Hepatitis C - blood; Hepatitis C - immunology; Hepatitis C - therapy; Human viral diseases; Humans; Infectious diseases; Interferon; Interferons - adverse effects; Interferons - therapeutic use; Male; Medical sciences; Meta-analysis; Middle Aged; Randomized Controlled Trials as Topic; Ribavirin; Ribavirin - therapeutic use; RNA, Viral - analysis; Therapy; Viral diseases; Viral hepatitis
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(97)80103-1

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-affiliated 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×/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.