Abstract

Objective: The aim of this study was to determine whether hepatic gene expression related to hepatocellular carcinoma (HCC) is associated with disease severity and modifiable lifestyle factors in non-alcoholic fatty liver disease (NAFLD). Methods: In a cross-sectional study, the associations between hepatic gene expression and liver histology, insulin resistance, anthropometrics, diet, and physical activity were assessed in patients with non-alcoholic steatohepatitis (NASH; n = 19) or simple steatosis (SS; n = 20). In a group of patients with NASH, we then conducted a 1-y, single-arm, pilot study using omega-3 polyunsaturated fatty acid (PUFA) supplementation to determine whether changes in hepatic PUFA content would have a modulating effect on hepatic gene expression and would affect liver histology. Results: In the cross-sectional study, histological features of disease severity correlated with AKR1B10, ANXA2, PEG10, SPP1, STMN2, MTIA, and MTIB in NASH and with EEFIA2, PEG10, and SPP1 in SS. In addition, PEG10, SPP1, ANXA2, and STMN2 expression correlated positively with insulin resistance in NASH. SPP1 and UBD correlated strongly with body mass index in SS. Associations between ENPP2, AKR1B10, SPP1, UBD, and waist circumference depended on sex and diagnosis. Several genes correlated with protein, fat, or carbohydrate intake. PEG10 correlated positively with physical activity in NASH and inversely with plasma vitamin C in both groups. Despite increased erythrocyte and hepatic omega-3 PUFA, supplementation did not alter hepatic gene expression and liver histology. Conclusions: HCC-related gene expression was associated with liver histology, body mass index, waist circumference, diet, and physical activity but was not affected by omega-3 PUFA supplementation. (C) 2018 Published by Elsevier Inc.