High doses of interferon in combination with ribavirin are more effective than the standard regimen in patients with HCV genotype 1 chronic hepatitis

Background/Aims: The aim of the present, open-labelled, controlled study was to determine whether 5 MU of interferon (IFN) alpha2b combined with a standard dose of ribavirin might increase the rate of viral clearance in all patients with chronic HCV hepatitis or at least in those with an unfavourable genotype. Methods: A total of 298 previously untreated patients with chronic hepatitis C were randomized to 5 or 3 MU of interferon alpha2b 3 times per week with 1000-1200 mg of ribavirin daily (148 and 150 patients, respectively). Patients were treated for 12 months and observed for 6 months posttreatment. Results: In patients infected with HCV genotype 1, the sustained virologic response was 37.8% (95% CI 27.3-48.1) with IFN 5 MU and 19.2 % (95 % CI 10.1-28.2) with IFN 3 MU (P = 0.008). Out of 45 sustained responders with genotype 1, 31 (69%) had received 5 MU and 14 (31.1%) the standard 3 MU dose of IFN in combination with ribavirin (P = 0.01). Of the 86 responders infected with genotype non-1, 39 (45.3%) were from the 5 MU IFN group and 47 (54.6%) were from the 3 MU IFN group; these figures were not significant. At the multivariate analysis of baseline features for all patients, the variables with an independent effect for a sustained response were genotype non-1 (odds ratio (OR) 3.98, 95% CI 2.36-6.40), and the histological grading (score 0-2) (OR 2.48, 95% CI 1.12-5.51) and staging (score 0-1) (OR 1.73, 95% CI 1.02-2.95). For patients with genotype 1 only the high regimen of IFN entered the model (OR 2.39, 95% CI 1.13-5.05), whereas for patients with genotype non-1 an age of <40 years (OR 2.64, 95% CI 1.23-5.70) and staging (score 0-1) (OR 2.38, 95% CI 1.07-5.28) were independent predictors of a sustained response. Conclusions: Our study suggests that when treating naive patients with genotype 1, there is a significant increase in the rate of sustained virologic clearance by increasing the dose of IFN given in combination with ribavirin. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved.