title: The pattern of pegylated interferon-alpha2b and ribavirin treatment failure in cirrhotic patients depends on hepatitis C virus genotype.
abstract: BACKGROUND
  Failure of anti-hepatitis C therapy encompasses both primary non-response and post-treatment relapse. Treatment failure to pegylated interferon (PEG-IFN)-alpha2b and ribavirin (RBV) largely depends upon virus genotype, but the interaction between genotype, cirrhosis and pattern of treatment failure is unclear. We aimed to assess whether cirrhosis modifies the pattern of PEG-IFN-alpha2b and RBV treatment failure.
  
  
  METHODS
  A total of 471 treatment-naive patients with histologically proven chronic hepatitis C virus (HCV) infection (106 with cirrhosis; 185 with HCV genotype 1 [HCV-1], 157 with HCV genotype 2 [HCV-2], 92 with HCV genotype 3 [HCV-3] and 37 with HCV genotype 4 [HCV-4]) were consecutively treated with PEG-IFN-alpha2b 1.5 microg weekly and weight-based RBV.
  
  
  RESULTS
  The sustained virological response (SVR) rates were 31% in HCV-1 and HCV-4, 80% in HCV-2 and 72% in HCV-3, and were lower in cirrhotic than in non-cirrhotic HCV-1 and HCV-4 (17% versus 36%; P=0.01), and HCV-3 (33% versus 79%; P=0.001), but not HCV-2 (69% versus 83%; P=0.1) patients. Treatment failure was the consequence of lower end-of-treatment response rates (37% versus 53%; P=0.06) plus higher post-treatment relapse rates (55% versus 31%; P=0.07) in cirrhotic HCV-1 and HCV-4 patients and higher rates of post-treatment relapse in HCV-2 (29% versus 10%; P=0.01) and HCV-3 cirrhotic patients (61% versus 12%; P<0.001). By multivariate analysis, HCV-1 and HCV-4 (odds ratio [OR] 7.44, 95% confidence interval [CI] 4.87-11.36), and cirrhosis (OR 3.00, 95% CI 1.80-5.00) were independent predictors of treatment failure.
  
  
  CONCLUSIONS
  Cirrhosis is an important moderator of SVR, accounting for different patterns of treatment failure in patients infected with different genotypes.
authors: AM Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Policlinico, Mangiagalli e Regina Elena, University of Milan, Milan, Italy.
authors: Alessio
authors: A
authors: Aghemo
authors: Maria Grazia
authors: MG
authors: Rumi
authors: Sara
authors: S
authors: Monico
authors: Gian Maria
authors: GM
authors: Prati
authors: Roberta
authors: R
authors: D'Ambrosio
authors: Maria Francesca
authors: MF
authors: Donato
authors: Massimo
authors: M
authors: Colombo
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; 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*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b