title: Hyporesponsiveness to PegIFNα2B plus ribavirin in patients with hepatitis C-related advanced fibrosis.
abstract: OBJECTIVE
  The success of pegylated-interferon (PegIFN)/ribavirin (Rbv) therapy of chronic hepatitis C is compromised by liver fibrosis. Whether fibrosis equally affects the two PegIFNα-based therapies is unknown. To assess the response to the two PegIFN regimens in patients with different degree of liver fibrosis.
  
  
  METHODS
  A sub-analysis of the MIST study: 431 consecutive naïve patients randomly assigned, based on HCV genotype, to receive either (A) PegIFNα2a 180 μg/wk plus daily Rbv 800-1200 mg or (B) PegIFNα2b 1.5 μg/kg/week plus daily Rbv 800-1200 mg, were stratified according to Ishak staging (S) into mild (S0-S2) or moderate (S3, S4) fibrosis and cirrhosis (S5, S6).
  
  
  RESULTS
  In A the sustained virological response (SVR) rates were not significantly influenced by fibrosis stage (71% in S0-S2, 66% in S3, S4, 53% in S5, S6, p=0.12), compared to B where the SVR rates differed according to fibrosis stage (65%, 46%, and 38%, p=0.004, respectively). This was even more so in HCV-1/4 patients treated with PegIFNα2b where the SVR rates were twice as many in S0-S2 vs. S≥3 (44% vs. 22%, p=0.02), while in A the SVR rates were similar between the two fibrosis subgroups (S0-S2: 47% vs. S≥3: 48%, p=0.8). By logistic regression analysis genotype 1/4 and lack of rapid virological response were independent predictors of treatment failure in both treatment groups, while S≥3 fibrosis was associated to PegIFNα2b treatment failure, only (OR 2.83, 95% CI 1.4-5.68, p=0.004).
  
  
  CONCLUSIONS
  Liver fibrosis was an independent moderator of treatment outcome in patients receiving PegIFNα2b, not in those receiving PegIFNα2a.
authors.affiliation: A.M. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Prati
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Rumi
authors.forename: Roberta
authors.initials: R
authors.lastname: D'Ambrosio
authors.forename: Stella
authors.initials: S
authors.lastname: De Nicola
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Donato
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Degasperi
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000145:classification / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a