The effect of the TM6SF2 E167K variant on liver steatosis and fibrosis in patients with chronic hepatitis C: a meta-analysis
Journal article, 2017

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 (I-2 = 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.


Z. T. Liu

Royal Institute of Technology (KTH)

Zhejiang University

S. P. Que

Women and Children's Hospital of Guangxi

L. Zhou

Zhejiang University

S. S. Zheng

Zhejiang University

S. Romeo

Magna Græcia University

University of Gothenburg

Adil Mardinoglu

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

L. Valenti

University of Milan

Ospedale Maggiore Policlinico Milano

Scientific Reports

2045-2322 (ISSN)

Vol. 7 1 9273- 9273

Subject Categories

Clinical Medicine



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