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

Mohammed Eslam, Ahmed M. Hashem, Reynold Leung, Manuel Romero-Gomez, Thomas Berg, Gregory J. Dore, Henry L. K. Chan, William L. Irving, David Sheridan, Maria L. Abate, Leon A. Adams, Alessandra Mangia, Martin Weltman, Elisabetta Bugianesi, Ulrich Spengler, Olfat Shaker, Janett Fischer, Lindsay Mollison, Wendy Cheng, Elizabeth PowellJacob Nattermann, Stephen Riordan, Duncan McLeod, Nicola J. Armstrong, Mark W. Douglas, Christopher Liddle, David R. Booth, Jacob George, Golo Ahlenstiel

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160 Citations (Scopus)

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.
Original languageEnglish
Article number6422
Number of pages10
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 2015

Open Access - Access Right Statement

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Keywords

  • fatty liver
  • fibrosis
  • genetic polymorphisms
  • genotype
  • hepatitis_viral

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