Interferon-λ rs12979860 Genotype and Liver Fibrosis in Viral and Non-Viral Chronic Liver Disease

Nat Commun. 2015 Mar 5;6:6422. doi: 10.1038/ncomms7422.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Female
  • Genotype
  • Hepatitis, Chronic / complications*
  • Humans
  • Interleukins / genetics*
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology*
  • Logistic Models
  • Non-alcoholic Fatty Liver Disease / complications*
  • Polymorphism, Single Nucleotide / genetics*
  • Sex Factors
  • Statistics, Nonparametric

Substances

  • IFNL4 protein, human
  • Interleukins