title: Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin.
abstract: OBJECTIVE
  Pegylated interferon alfa-ribavirin combination is the standard treatment for chronic hepatitis C, but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus (HCV) eradication remain unknown. We aimed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24.
  
  
  METHODS
  A total of 516 patients were treated with pegylated interferon alfa-2a, 180 microg/wk, plus ribavirin, 800 mg/day. Seventy percent were RNA negative at week 24. They were randomized to continue with the combination or receive pegylated interferon alone.
  
  
  RESULTS
  Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during, and relapses after, therapy (sustained virologic response, 52.8% vs 68.2%; P = .004), but their side-effect profile and quality of life tended to improve. Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response, based on baseline viral load and age. Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2.
  
  
  CONCLUSIONS
  We made 3 conclusions from this study. First, ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa; second, ribavirin must be administered for the full treatment duration in most genotype 1-infected patients who respond; third, baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success.
authors.affiliation: Department of Hepatology and Gastroenterology, INSERM U724, CHU de Nancy, Vandoeuvre-les-Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Denis
authors.initials: D
authors.lastname: Ouzan
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.forename: Hervé
authors.initials: H
authors.lastname: Desmorat
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
authors.forename: Juliette
authors.initials: J
authors.lastname: Foucher
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.forename: Christophe
authors.initials: C
authors.lastname: Renou
authors.forename: Albert
authors.initials: A
authors.lastname: Tran
authors.forename: Pascal
authors.initials: P
authors.lastname: Melin
authors.forename: Christophe
authors.initials: C
authors.lastname: Hézode
authors.forename: Michelle
authors.initials: M
authors.lastname: Chevalier
authors.forename: Magali
authors.initials: M
authors.lastname: Bouvier-Alias
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chevaliez
authors.forename: François
authors.initials: F
authors.lastname: Montestruc
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lonjon-Domanec
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D012367:RNA, Viral / Q000097:blood; 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; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a