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J Hepatol. 2014 Aug;61(2):235-41. doi: 10.1016/j.jhep.2014.03.039. Epub 2014 Apr 24.

IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection.

Author information

1
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia.
2
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia; Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, NSW, Australia.
3
Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain.
4
Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy.
5
NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham, UK.
6
Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
7
Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
8
Fremantle Hepatitis Services, Fremantle, Australia.
9
Department of Gastroenterology and Hepatology, Royal Perth Hospital, Western Australia, Australia.
10
Division of Gastro-Hepatology, S. Giovanni Battista Hospital, Turin, Italy.
11
Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, Australia.
12
Department of Histopathology, University Hospital Queens Medical Centre, Nottingham, UK.
13
Department is Anatoma Patologica IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
14
Pathologisches Institute, Universitaetsklinikum Bonn, Germany.
15
Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, NSW, Australia.
16
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia. Electronic address: jacob.george@sydney.edu.au.

Abstract

BACKGROUND & AIMS:

Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients.

METHODS:

The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917.

RESULTS:

Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG).

CONCLUSIONS:

This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients.

KEYWORDS:

Chronic hepatitis C; Genotype 2; Genotype 3; IFNL3 (IL28B); Response to therapy; SVR

PMID:
24768758
DOI:
10.1016/j.jhep.2014.03.039
[Indexed for MEDLINE]

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