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Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients
Author(s) -
Milano Marta,
Aghemo Alessio,
Mancina Rosellina Margherita,
Fischer Janett,
Dongiovanni Paola,
De Nicola Stella,
Fracanzani Anna Ludovica,
D'Ambrosio Roberta,
Maggioni Marco,
De Francesco Raffaele,
Fargion Silvia,
Berg Thomas,
Stickel Felix,
Hampe Jochen,
Romeo Stefano,
Colombo Massimo,
Valenti Luca
Publication year - 2015
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.27811
Subject(s) - steatosis , gastroenterology , medicine , cirrhosis , odds ratio , fibrosis , nonalcoholic fatty liver disease , fatty liver , hepatitis c , disease
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 < 0.001). In Swiss/German patients, the E167K variant was independently associated with clinically significant fibrosis Metavir stage F2‐F4 (OR, 1.81; 95% CI: 1.12‐3.02; P = 0.016). Conclusion: TM6SF2 E167K variant impacts on steatosis severity and is associated with liver damage and fibrosis in patients with CHC. (H epatology 2015;62:111‐117)