The effect of the TM6SF2 E167K variant on liver steatosis and fibrosis in patients with chronic hepatitis C: a meta-analysis

Sci Rep. 2017 Aug 24;7(1):9273. doi: 10.1038/s41598-017-09548-9.


The impact of Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant, which causes hepatocellular fat retention by altering lipoprotein secretion, on liver damage and metabolic traits in chronic hepatitis C patients is still debated. We performed a systematic review and meta-analysis to clarify this relationship. Four studies with a total of 4325 patients were included. The risk of histologically-determined advanced steatosis, fibrosis, and cirrhosis (but not of severe inflammation) were increased in carriers of the TM6SF2 variant (P < 0.05). Unlike the inconsistent association with steatosis severity, due to the confounding effect of infection by the genotype-3 hepatitis C virus, the TM6SF2 variant was robustly associated with advanced fibrosis (OR = 1.07; 95% confidence interval [CI] = 1.01-1.14) and in particular with cirrhosis (OR = 2.05; 95% CI = 1.39-3.02). Regarding metabolic features, individuals positive for the TM6SF2 variant exhibited 5.8-12.0% lower levels of circulating triglycerides and non-HDL cholesterol (P < 0.05). Carriers of the variant were leaner, but there was high heterogeneity across studies (I2 = 97.2%). No significant association was observed between the TM6SF2 variant and insulin resistance or hepatitis C viral load (both P > 0.05). In conclusion, the TM6SF2 E167K variant promotes the development of steatosis, fibrosis and cirrhosis in patients with chronic hepatitis C. Conversely, this variant reduces circulating atherogenic lipid fractions.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Amino Acid Substitution
  • Biomarkers
  • Fatty Liver / diagnosis
  • Fatty Liver / etiology*
  • Fatty Liver / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Humans
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation*
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Publication Bias
  • Quantitative Trait, Heritable
  • Viral Load


  • Biomarkers
  • Membrane Proteins
  • TM6SF2 protein, human