Meta-analysis 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 or of longer duration in comparison with a standard interferon regimen (3 MU three times per week for 6 months) in chronic hepatitis C, and to assess the efficacy of interferon in acute hepatitis C. Meta-analysis made use of the Peto et al. and the Der Simonian and Laird methods, with heterogeneity and sensitivity analyses. In chronic hepatitis, a total 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 complete alanine transaminase (ALT) response rate and sustained (ALT) response rate by 45% (95% confidence interval: 35% to 55%; P < .001) and 21% (13% to 28%; P < .001), respectively, with the natural course being less than 2% of spontaneous responses. There was a significant dose effect (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 controls (4 trials), upon the complete ALT response (69% vs. 29%; P < .001), the sustained response rate during the 12 months following treatment (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 chronic hepatitis C who had never been treated with interferon. Patients with acute hepatitis should be treated with at least 3 MU three times per week for 3 months.
Poynard
T
T
Service d'Hépato-Gastroenterologie, Group Hospitalier Pitié-Saltpêtrière, CNRS URA 1484, Paris, France.
Leroy
V
V
Cohard
M
M
Thevenot
T
T
Mathurin
P
P
Opolon
P
P
Zarski
J P
JP
D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006526:Hepatitis C / Q000201:enzymology / Q000628:therapy*; D006521:Hepatitis, Chronic / Q000201:enzymology / Q000628:therapy*; D006801:Humans; D007372:Interferons / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction
D000998:Antiviral Agents; D007372:Interferons; D000410:Alanine Transaminase