IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection.
OBJECTIVE
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.
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia.
Mohammed
M
Eslam
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.
Reynold
R
Leung
Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain.
Manuel
M
Romero-Gomez
Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy.
Alessandra
A
Mangia
NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham, UK.
William L
WL
Irving
Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
David
D
Sheridan
Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
Ulrich
U
Spengler
Fremantle Hepatitis Services, Fremantle, Australia.
Lindsay
L
Mollison
Department of Gastroenterology and Hepatology, Royal Perth Hospital, Western Australia, Australia.
Wendy
W
Cheng
Division of Gastro-Hepatology, S. Giovanni Battista Hospital, Turin, Italy.
Elisabetta
E
Bugianesi
Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, Australia.
Duncan
D
McLeod
Department of Histopathology, University Hospital Queens Medical Centre, Nottingham, UK.
Abed M
AM
Zaitoun
Department is Anatoma Patologica IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
Vito
V
Attino
Pathologisches Institute, Universitaetsklinikum Bonn, Germany.
Diane
D
Goeltz
Department of Internal Medicine I, University of Bonn, Sigmund-Freud-Strasse, Bonn, Germany.
Jacob
J
Nattermann
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia.
Mark
M
Douglas
Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, NSW, Australia.
David R
DR
Booth
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia. Electronic address: jacob.george@sydney.edu.au.
Jacob
J
George
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia.
Golo
G
Ahlenstiel
D000328:Adult; D000368:Aged; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
Chronic hepatitis C; Genotype 2; Genotype 3; IFNL3 (IL28B); Response to therapy; SVR