EFFECT OF RECOMBINANT OR LYMPHOBLASTOID INTERFERON-ALPHA ON ALANINE, AMINOTRANSFERASE IN PATIENTS WITH CHRONIC HEPATITIS-C OR CHRONIC NON-A NON-B-HEPATITIS - A METAANALYSIS

A meta-analysis of published randomised clinical trials was performed to determine the efficacy of recombinant and lymphoblastoid interferon-alpha (IFN alpha) in the induction and maintenance of remission in patients with chronic C or non-A non-B hepatitis. Studies were identified using standard computer techniques for literature searches and by reviewing all references of the papers examined. Each trial evaluated the efficacy of IFN alpha (recombinant and lymphoblastoid)(1) in comparison with a control group receiving either placebo or no treatment. Since the end-point of the analysis was of a censored-type [i.e. normalisation of alanine aminotransferase (ALT) levels over time], a specific method of meta-analysis was employed that allowed the inclusion of trials of different durations and permitted determination of the probability of therapeutic success over time. Two separate meta-analyses were carried out to address (a) the efficacy of IFN alpha during treatment (first meta-analysis) and (b) the relapse risk after drug discontinuation (second meta-analysis). 21 trials were included in the evaluation: 16 used recombinant IFN alpha and 5 used lymphoblastoid IFN alpha. Results of the first meta-analysis indicated that IFN alpha was highly effective at inducing ALT normalisation [log-rank odds-ratio (95% CI): 8.4 (6.3-11.2) at 24 weeks and 8.2 (6.2-10.9) at 48 weeks]. The pooled meta-analytical rate of ALT normalisation in the treatment group was 37% at 24 weeks and 44% at 48 weeks. Results of the second meta-analysis conducted in the subgroup of patients that achieved stable ALT normalisation following IFN alpha treatment revealed that remission was maintained after drug discontinuation in 47% of patients (pooled meta-analytical rate after a follow-up period of 12 to 60 weeks). Relapse-free remission during the follow-up period was 59% in patients treated with lymphoblastoid IFN alpha versus 43% in patients treated with recombinant IFN alpha. Taking into consideration the results of both meta-analyses, the global rate of success, i.e. the probability of achieving remission with treatment and of maintaining remission after drug discontinuation, is 17.4% at 24 weeks of IFN alpha therapy. If the studies are stratified according to the type of IFN alpha administered, the global rates of success are 16% for recombinant IFN alpha and 25% for lymphoblastoid IFN alpha.