title: High doses of interferon in combination with ribavirin are more effective than the standard regimen in patients with HCV genotype 1 chronic hepatitis.
abstract: OBJECTIVE
  The aim of the present, open-labelled, controlled study was to determine whether 5 MU of interferon (IFN) alpha 2b 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 alpha 2b 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.
authors.affiliation: Division of Gastroenterology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy. a.mangia@tin.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.forename: Rosanna
authors.initials: R
authors.lastname: Santoro
authors.forename: Marisa
authors.initials: M
authors.lastname: Piattelli
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Leandro
authors.forename: Nicola
authors.initials: N
authors.lastname: Minerva
authors.forename: Mauro
authors.initials: M
authors.lastname: Annese
authors.forename: Donato
authors.initials: D
authors.lastname: Bacca
authors.forename: Fulvio
authors.initials: F
authors.lastname: Spirito
authors.forename: Vito
authors.initials: V
authors.lastname: Carretta
authors.forename: Francesco
authors.initials: F
authors.lastname: Ventrella
authors.forename: Marina
authors.initials: M
authors.lastname: Cela
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin