Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease.
Tissue fibrosis is a core pathologic process that contributes to mortality in ~45% of the population and is likely to be influenced by the host genetic architecture. Here we demonstrate, using liver disease as a model, that a single-nucleotide polymorphism (rs12979860) in the intronic region of interferon-λ4 (IFNL4) is a strong predictor of fibrosis in an aetiology-independent manner. In a cohort of 4,172 patients, including 3,129 with chronic hepatitis C (CHC), 555 with chronic hepatitis B (CHB) and 488 with non-alcoholic fatty liver disease (NAFLD), those with rs12979860CC have greater hepatic inflammation and fibrosis. In CHC, those with rs12979860CC also have greater stage-constant and stage-specific fibrosis progression rates (P<0.0001 for all). The impact of rs12979860 genotypes on fibrosis is maximal in young females, especially those with HCV genotype 3. These findings establish rs12979860 genotype as a strong aetiology-independent predictor of tissue inflammation and fibrosis.
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
Mohammed
M
Eslam
Faculty of Engineering, Department of Systems and Biomedical Engineering, Minia University, Minia 6111, Egypt.
Ahmed M
AM
Hashem
1] Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia [2] Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, Sydney, New South Wales 2145, Australia.
Reynold
R
Leung
Unit for The Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla 41014, Spain.
Manuel
M
Romero-Gomez
1] Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charite, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin 04103, Germany [2] Department of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig 04103, Germany.
Thomas
T
Berg
1] Kirby Institute, The University of New South Wales, Sydney, New South Wales 2052, Australia [2] St Vincent's Hospital, Sydney, New South Wales 2052, Australia.
Gregory J
GJ
Dore
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Henry L K
HL
Chan
NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham NG7 2UH, UK.
William L
WL
Irving
1] Liver Research Group, Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK [2] Institute of Translational and Stratified Medicine, Plymouth University, Plymouth PL4 8AA, UK.
David
D
Sheridan
Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin 10126, Italy.
Maria L
ML
Abate
School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of Western Australia, Nedlands, Western Australia 6009, Australia.
Leon A
LA
Adams
Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo 71013, Italy.
Alessandra
A
Mangia
Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney, New South Wales 2747, Australia.
Martin
M
Weltman
Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin 10126, Italy.
Elisabetta
E
Bugianesi
Department of Internal Medicine I, University of Bonn, Bonn 53105, Germany.
Ulrich
U
Spengler
Faculty of Medicine, Medical Biochemistry and Molecular Biology Department, Cairo University, Cairo 11562, Egypt.
Olfat
O
Shaker
Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Charite, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin 04103, Germany.
Janett
J
Fischer
Department of Gastroenterology and Hepatology, Fremantle Hospital, Fremantle, Western Australia 6160, Australia.
Lindsay
L
Mollison
Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Western Australia 6000, Australia.
Wendy
W
Cheng
1] Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia [2] The University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, Queensland 4072, Australia.
Elizabeth
E
Powell
Department of Internal Medicine I, University of Bonn, Bonn 53105, Germany.
Jacob
J
Nattermann
Gastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, New South Wales 2031, Australia.
Stephen
S
Riordan
Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research (ICPMR), Westmead Hospital, Sydney, New South Wales 2145, Australia.
Duncan
D
McLeod
School of Mathematics and Statistics, University of Sydney, Sydney, New South Wales 2006, Australia.
Nicola J
NJ
Armstrong
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
Mark W
MW
Douglas
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
Christopher
C
Liddle
Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, Sydney, New South Wales 2145, Australia.
David R
DR
Booth
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
Jacob
J
George
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales 2145, Australia.
Golo
G
Ahlenstiel
D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006521:Hepatitis, Chronic / Q000150:complications*; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016015:Logistic Models; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012737:Sex Factors; D018709:Statistics, Nonparametric; D000095022:Interferon Lambda
D007378:Interleukins; C579163:IFNL4 protein, human; D000095022:Interferon Lambda