Abstract
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.
Highlights
A comprehensive search for literature addressing the genetic associations of TM6SF2 variants on hepatic steatosis and relevant complications in patients with CHC was conducted using the Medline, EMBASE, and the Cochrane Library databases without language restriction
Additional information concerning the association between the TM6SF2 E167K polymorphism and specific histological features including the scoring system, number of patients with different disease severities classified by TM6SF2 variants, comparisons, corresponding odds ratios (ORs), and adjusted covariates were collected
For covariates reported in participants with CT and TT genotypes, the data were combined according to the number (N), mean and standard deviation (SD) using pre-defined formulas[45]
Summary
A comprehensive search for literature addressing the genetic associations of TM6SF2 variants on hepatic steatosis and relevant complications in patients with CHC was conducted using the Medline, EMBASE, and the Cochrane Library databases without language restriction (updated until May 20, 2017). Histological features were assessed via liver biopsy under the guidance of a pre-defined scoring system; 4. The risk of hazardous variants on the susceptibility of hepatic histological lesions was reported or could be calculated.
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