METAANALYSIS OF INTERFERON RANDOMIZED TRIALS IN THE TREATMENT OF VIRAL-HEPATITIS-C - EFFECTS OF DOSE AND DURATION

The aims of this study were to evaluate the benefits of higher doses o r of longer duration in comparison with a standard interferon regimen (3 MU three times per week for 6 months) in chronic hepatitis C, and t o assess the efficacy of interferon in acute hepatitis C. Meta-analysi s made use of the Peto et al. and the Per Simonian and Laird methods, with heterogeneity and sensitivity analyses. In chronic hepatitis, a t otal of 17 trials versus controls and of 16 trials comparing different interferon regimens were included. Standard regimen, 3 MU three times per week for 6 months, was associated with an increase of the complet e alanine transaminase (ALT) response rate and sustained (ALT) respons e rate by 45% (95% confidence interval: 35% to 55%; P < .001) and 21% (13% to 28%; P < .001), respectively, with the natural course being le ss than 2% of spontaneous responses. There was a significant dose effe ct (6 vs. 3 MU three times per week) upon the sustained response rate at 12 months, with a mean 17% increase (7% to 28%; P < .001), but not at 6 months. There was a significant duration effect (12 vs. 6 months) upon the sustained response rate both at the dose of 3 MU with a mean of 16% (9% to 23%; P < .001), and at the dose of 6 MU three times per week with a mean of 20% (7% to 33%; P = .003). In acute hepatitis C, 3 months of interferon treatment showed significant efficacy versus co ntrols (4 trials), upon the complete ALT response (69% vs. 29%; P < .0 01), the sustained response rate during the 12 months following treatm ent (53% vs. 32%; P = .02), and hepatitis C virus (HCV)-RNA clearance (41% vs. 4%; P < .001). The best efficacy/risk ratio was in favor of 3 MU three times per week for at least 12 months in patients with chron ic hepatitis C who had never been treated with interferon. Patients wi th acute hepatitis should be treated with at least 3 MU three times pe r week for 3 months.