Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease

M. Eslam; A.M. Hashem; R. Leung; M. Romero-Gomez; T. Berg; G.J. Dore; H.L.K. Chan; W.L. Irving; D. Sheridan; M.L. Abate; L.A. Adams; A. Mangia; M. Weltman; E. Bugianesi; U. Spengler; O. Shaker; J. Fischer; L. Mollison; W. Cheng; E. Powell; J. Nattermann; S. Riordan; D. McLeod; N.J. Armstrong; M.W. Douglas; C. Liddle; D.R. Booth; J. George; G. Ahlenstiel; J. Ampuero; M. Bassendine; V.W.S. Wong; C. Rosso; R. White; L. Mezzabotta; V. Suppiah; M. Michalk; B. Malik; G. Matthews; T. Applegate; J. Grebely; V. Fragomeli; J.R. Jonsson; R. Santaro

doi:10.1038/ncomms7422

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Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease

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Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease

M. Eslam, A.M. Hashem, R. Leung, M. Romero-Gomez, T. Berg, G.J. Dore, H.L.K. Chan, W.L. Irving, D. Sheridan, M.L. Abate, …

Nature Communications, Vol.6

2015

DOI: https://doi.org/10.1038/ncomms7422

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Abstract

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.

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Title: Interferon-λ rs12979860 genotype and liver fibrosis in viral and non-viral chronic liver disease
Authors/Creators: M. Eslam (Author/Creator) - The University of Sydney
A.M. Hashem (Author/Creator) - Minia University
R. Leung (Author/Creator) - The University of Sydney
M. Romero-Gomez (Author/Creator) - Hospital Universitario de Valme
T. Berg (Author/Creator) - University of Leipzig
G.J. Dore (Author/Creator) - St Vincent's Hospital Sydney
H.L.K. Chan (Author/Creator) - Chinese University of Hong Kong
W.L. Irving (Author/Creator) - University of Nottingham
D. Sheridan (Author/Creator) - University of Plymouth
M.L. Abate (Author/Creator) - University of Turin
L.A. Adams (Author/Creator) - School of Medicine and Pharmacology
A. Mangia (Author/Creator) - Casa Sollievo della Sofferenza
M. Weltman (Author/Creator) - Nepean Hospital
E. Bugianesi (Author/Creator) - University of Turin
U. Spengler (Author/Creator) - University of Bonn
O. Shaker (Author/Creator) - Cairo University
J. Fischer (Author/Creator) - Charité - Universitätsmedizin Berlin
L. Mollison (Author/Creator) - Fremantle Hospital
W. Cheng (Author/Creator) - Royal Perth Hospital
E. Powell (Author/Creator) - The University of Queensland
J. Nattermann (Author/Creator) - University of Bonn
S. Riordan (Author/Creator) - UNSW Sydney
D. McLeod (Author/Creator) - Westmead Hospital
N.J. Armstrong (Author/Creator) - The University of Sydney
M.W. Douglas (Author/Creator) - The University of Sydney
C. Liddle (Author/Creator) - The University of Sydney
D.R. Booth (Author/Creator) - The University of Sydney
J. George (Author/Creator) - The University of Sydney
G. Ahlenstiel (Author/Creator) - The University of Sydney
J. Ampuero (Author/Creator) - Hospital Universitario de Valme
M. Bassendine (Author/Creator) - Newcastle University
V.W.S. Wong (Author/Creator) - Chinese University of Hong Kong
C. Rosso (Author/Creator) - University of Turin
R. White (Author/Creator) - The University of Sydney
L. Mezzabotta (Author/Creator) - University of Turin
V. Suppiah (Author/Creator) - The University of Sydney
M. Michalk (Author/Creator) - University of Bonn
B. Malik (Author/Creator) - Charité - Universitätsmedizin Berlin
G. Matthews (Author/Creator) - UNSW Sydney
T. Applegate (Author/Creator) - UNSW Sydney
J. Grebely (Author/Creator) - UNSW Sydney
V. Fragomeli (Author/Creator) - Nepean Hospital
J.R. Jonsson (Author/Creator) - Princess Alexandra Hospital
R. Santaro (Author/Creator) - Casa Sollievo della Sofferenza
Publication Details: Nature Communications, Vol.6
Publisher: Nature Publishing Group
Identifiers: 991005542484107891
Copyright: © 2015 Macmillan Publishers Limited.
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.125 Hepatitis; 1.125.83 HCV
Web Of Science research areas: Gastroenterology & Hepatology
ESI research areas: Clinical Medicine