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

Lookup NU author(s): Dr David Sheridan, Professor Margaret Bassendine

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Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. 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.

Publication metadata

Author(s): Eslam M, Hashem AM, Leung R, Romero-Gomez M, Berg T, Dore GJ, Chan HLK, Irving WL, Sheridan D, Abate ML, Adams LA, Mangia A, Weltman M, Bugianesi E, Spengler U, Shaker O, Fischer J, Mollison L, Cheng W, Powell E, Nattermann J, Riordan S, McLeod D, Armstrong NJ, Douglas MW, Liddle C, Booth DR, George J, Ahlenstiel G, Ampuero J, Bassendine M, Wong VWS, Rosso C, White R, Mezzabotta L, Suppiah V, Michalk M, Malik B, Matthews G, Applegate T, Grebely J, Fragomeli V, Jonsson JR, Santaro R

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2015

Volume: 6

Online publication date: 05/03/2015

Acceptance date: 28/01/2015

ISSN (print): 2041-1723

Publisher: Nature Publishing Group

URL: http://doi.org/10.1038/ncomms7422

DOI: 10.1038/ncomms7422

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