Ribavirin enhances the efficacy but not the adverse effects of interferon in chronic hepatitis C. Meta-analysis of individual patient data from European centers.
OBJECTIVE
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 3x/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.
Schalm
S W
SW
Department of Hepatogastroenterology, Erasmus University Rotterdam, The Netherlands. schalm@inw2.azr.nl
Hansen
B E
BE
Chemello
L
L
Bellobuono
A
A
Brouwer
J T
JT
Weiland
O
O
Cavalletto
L
L
Schvarcz
R
R
Ideo
G
G
Alberti
A
A
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D002908:Chronic Disease; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000097:blood / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007372:Interferons / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D016032:Randomized Controlled Trials as Topic; D012254:Ribavirin / Q000627:therapeutic use*
D006454:Hemoglobins; D012367:RNA, Viral; D012254:Ribavirin; D007372:Interferons; D000410:Alanine Transaminase