title: High-dose pegylated interferon-α and ribavirin in nonresponder hepatitis C patients and relationship with IL-28B genotype (SYREN trial).
abstract: OBJECTIVE
  In patients with chronic hepatitis C who failed to respond to standard therapy, high-dose pegylated interferon (IFN)-α and/or ribavirin could induce a stronger antiviral response and prevent treatment failure and HCV resistance when combined with direct-acting antivirals. The influence of genetic determinants in this context remains unknown.
  
  
  METHODS
  Eighty-three patients infected with HCV genotype 1 who were nonresponsive to standard therapy received pegylated IFN-α2a (360 μg once per week or 180 μg twice per week) with ribavirin (1.0-1.2 or 1.2-1.6 g/d) for up to 72 weeks. Virological responses were assessed at different time points, and the influence of the IL-28B genotype was studied.
  
  
  RESULTS
  At weeks 12 and 24, respectively, 47 (56.6%) and 50 (60.2%) patients achieved a ≥2-Log10 decrease of HCV RNA levels; 8 (9.6%) and 21 (25.3%) patients had undetectable HCV RNA after 12 and 24 weeks of treatment, respectively. Patients with a CT IL-28B genotype responded significantly better and earlier than those with a TT genotype. In multivariate analysis, the IL-28B genotype was an independent predictor of the virological responses at weeks 4, 12, and 24.
  
  
  CONCLUSIONS
  High-dose pegylated IFN-α with standard or high doses of ribavirin induces a potent antiviral response in a substantial number of patients who did not respond to standard therapy. The IL-28B genotype is an independent predictor of the antiviral response. High-dose pegylated IFN-α in combination with ribavirin and protease inhibitors appears as an attractive option for future study in this population.
authors: National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, INSERM U955, Créteil, France.
authors: Stéphane
authors: S
authors: Chevaliez
authors: Christophe
authors: C
authors: Hézode
authors: Alexandre
authors: A
authors: Soulier
authors: Bruno
authors: B
authors: Costes
authors: Magali
authors: M
authors: Bouvier-Alias
authors: Stéphanie
authors: S
authors: Rouanet
authors: Juliette
authors: J
authors: Foucher
authors: Jean-Pierre
authors: JP
authors: Bronowicki
authors: Albert
authors: A
authors: Tran
authors: Isabelle
authors: I
authors: Rosa
authors: Philippe
authors: P
authors: Mathurin
authors: Laurent
authors: L
authors: Alric
authors: Vincent
authors: V
authors: Leroy
authors: Patrice
authors: P
authors: Couzigou
authors: Ariane
authors: A
authors: Mallat
authors: Mariem
authors: M
authors: Charaf-Eddine
authors: Gérard
authors: G
authors: Babany
authors: Jean-Michel
authors: JM
authors: Pawlotsky
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a