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

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-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.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Chevaliez S,Hézode C,Soulier A,Costes B,Bouvier-Alias M,Rouanet S,Foucher J,Bronowicki JP,Tran A,Rosa I,Mathurin P,Alric L,Leroy V,Couzigou P,Mallat A,Charaf-Eddine M,Babany G,Pawlotsky JM

doi

10.1053/j.gastro.2011.03.039

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

119-27

issue

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(11)00382-9

journal_volume

141

pub_type

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