High-dose pegylated interferon-α and ribavirin in nonresponder hepatitis C patients and relationship with IL-28B genotype (SYREN trial).

نویسندگان

  • Stéphane Chevaliez
  • Christophe Hézode
  • Alexandre Soulier
  • Bruno Costes
  • Magali Bouvier-Alias
  • Stéphanie Rouanet
  • Juliette Foucher
  • Jean-Pierre Bronowicki
  • Albert Tran
  • Isabelle Rosa
  • Philippe Mathurin
  • Laurent Alric
  • Vincent Leroy
  • Patrice Couzigou
  • Ariane Mallat
  • Mariem Charaf-Eddine
  • Gérard Babany
  • Jean-Michel Pawlotsky
چکیده

BACKGROUND & AIMS 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.

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Polymorphism of IL-28B Gene (rs12979860) in HCV Genotype 1 Patients Treated by Pegylated Interferon and Ribavirin

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عنوان ژورنال:
  • Gastroenterology

دوره 141 1  شماره 

صفحات  -

تاریخ انتشار 2011