High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial).

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

doi:10.1053/j.gastro.2011.03.039

High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial).: High-Dose peg-IFN and Ribavirin and IL28B in HCV nonresponders

Stéphane Chevaliez ^{1, 2} Christophe Hézode ^{1, 3} Alexandre Soulier ^{1, 2} Bruno Costes ^{2, 4} Magali Bouvier-Alias ^{1, 2} Stéphanie Rouanet ⁵ Juliette Foucher ⁶ Jean-Pierre Bronowicki ⁷ Albert Tran ⁸ Isabelle Rosa ⁹ Philippe Mathurin ¹⁰ Laurent Alric ¹¹ Vincent Leroy ¹² Patrice Couzigou ⁶ Ariane Mallat ^{1, 3} Mariem Charaf-Eddine ⁵ Gérard Babany ⁵ Jean-Michel Pawlotsky ^{1, 2, *}

* Auteur correspondant

1 Centre National de Référence Virus des hépatites B, C et Delta

2 IMRB - Institut Mondor de Recherche Biomédicale

3 Service d'hépato-gastro-entérologie [APHP Henri Mondor]

4 Service de Biochimie [Mondor]

5 Produits Roche

6 Département d'hépatologie et de gastroentérologie

7 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux

8 Pôle Digestif

9 Service d'hépato-gastro-entérologie

10 Service d'Hépato-gastroentérologie

11 Service de médecine interne et maladies digestives

12 Département d'hépatologie et de gastroentérologie

Abstract : 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-Log(10) 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.

Keywords : Hepatitis C virus nonresponder high-dose pegylated IFN-α IL28B genotype

Type de document :

Article dans une revue

Gastroenterology, WB Saunders, 2011, 141 (1), pp.119-27. 〈10.1053/j.gastro.2011.03.039〉

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire

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http://www.hal.inserm.fr/inserm-00611186
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High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial).: High-Dose peg-IFN and Ribavirin and IL28B in HCV nonresponders

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High-Dose Pegylated Interferon-α and Ribavirin in Nonresponder Hepatitis C Patients and Relationship With IL-28B Genotype (SYREN Trial).: High-Dose peg-IFN and Ribavirin and IL28B in HCV nonresponders

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