Combination Therapy of Chronic Hepatitis C with Ribavirin and Interferon

Learning Objective:

To review the efficacy and tolerability of interferon-ribavirin combination therapy in HCV in general and in specific subgroups (genotype 1, cirrhosis)


A meta-analysis of individual patient data from four European studies, comprising about 90% of the published experience with interferon-ribavirin combination therapy, was carried out to obtain a more precise estimation of the efficacy and tolerability of combination therapy for chronic hepatitis C.

Data were collected on 186 individuals who had participated in three randomized controlled trials and one open study, performed in four European university-affiliated liver referral centres. Fifty-one patients had received ribavirin monotherapy (1000-1200 mg/day), 37 interferon monotherapy (3 MU 3x/week) and 78 interferon-ribavirin combination therapy (dosage as for monotherapies) for six months; 20 patients received ribavirin placebo and served as controls. Follow-up after therapy was six months. The major outcome measures were the sustained response rate, defined as normal ALT levels and undetectable HCV RNA at six months after the end of therapy, and the percentage withdrawals because of adverse effects.

To correct for the effect of differences in pretreatment characteristics between the four studies (treatment centre, previous therapy, age, genotype, cirrhosis, etc.), the data were collected per individual patient and analysed by the multivariate logistical regression method.

The sustained response rate was significantly higher for interferon-ribavirin combination therapy than for interferon or ribavirin monotherapy (odds ratio IFN-Ribo vs IFN: 7.3, 95% CI 1.9-50); this rate was independent of subgroups such as cirrhosis or genotype 1. 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 19% for previous IFN non-responders.

Tolerability of the interferon-ribavirin combination appears to be clinically acceptable with no serious adverse events observed and less than 10% withdrawal. Figure 3 IFN-Riba Therapy Adverse Effect: Anemia Hb mmol/L (mean) Cumulative % Hb <9.6 g/L.

This meta-analysis of individual data strongly suggests a two to three-fold enhanced efficacy of interferon-ribavirin combination therapy 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.

* For the Eurohep meta-analysis of individual data group: Schalm SW, Hansen B, Chemello L, Cavalletto L, Bellobuono A, Weiland O, Schvaro R, Ideo G, Alberti A.


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