Transmembrane 6 Superfamily Member 2 Gene E167K Variant Impacts on Steatosis and Liver Damage in Chronic Hepatitis C Patients

Marta Milano, Alessio Aghemo, Rosellina Margherita Mancina, Janett Fischer, Paola Dongiovanni, Stella De Nicola, Anna Ludovica Fracanzani, Roberta D'Ambrosio, Marco Maggioni, Raffaele De Francesco, Silvia Fargion, Thomas Berg, Felix Stickel, Jochen Hampe, Stefano Romeo, Massimo Colombo, Luca Valenti

Research output: Contribution to journalArticle

Abstract

Steatosis and inherited host factors influence liver damage progression in chronic hepatitis C (CHC). The transmembrane 6 superfamily member 2 (TM6SF2) gene E167K variant increases liver fat and risk of progressive steatohepatitis by interfering with lipoprotein secretion. Our aim was to determine whether the E167K variant affects histological severity of steatosis, necroinflammation, and fibrosis in a cross-sectional cohort of 815 Italian therapy-naïve CHC patients. The association with clinically significant fibrosis was replicated in 645 Swiss/German patients. The TM6SF2 E167K variant was genotyped by TaqMan assays, steatosis graded according to the nonalcoholic fatty liver disease activity score, and necroinflammation and fibrosis graded and staged according to Ishak in Italian, and to Metavir in Swiss/German patients. The E167K variant was detected in 69 (9%) Italian patients and was associated with more severe steatosis, independently of confounders (P=0.038). The association between E167K and steatosis severity was present in patients not infected by genotype 3 (G3) HCV (P=0.031), but not in those infected by G3 HCV (P=0.58). Furthermore, the E167K variant was associated with more severe necroinflammation (Ishak grade; adjusted P=0.037) and nearly associated with more severe fibrosis (Ishak stage; adjusted P=0.058). At multivariate logistic regression analysis, the E167K variant was independently associated with histologically probable or definite cirrhosis (Ishak stage S6; odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.18-3.93; P=0.010). After further conditioning for steatosis and necroinflammation, the E167K variant remained associated with cirrhosis (OR, 3.15; 95% CI: 1.60-5.99; P

Original languageEnglish
Pages (from-to)111-117
Number of pages7
JournalHepatology
Volume62
Issue number1
DOIs
Publication statusPublished - Jul 1 2015

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

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