P0981 : Adaptation of hepatic mitochondrial function in obese humans with or without non-alcoholic steatohepatitis

Abstract

Background and Aims: Patients with non-alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth. We aimed to test the hypothesis that endotoxaemia is associated with fatty liver in the general population and to study dietary factors associated with endotoxaemia. Methods: Community adult subjects were randomly selected from the Hong Kong Government’s census database and underwent proton-magnetic resonance spectroscopy and transient elastography to assess hepatic steatosis and fibrosis, respectively. Intrahepatic triglyceride content (IHTG) of 5% was the cutoff to define fatty liver. Endotoxaemia was assessed using the Limulus Amebocyte Lysate, lipopolysaccharide-binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays. Dietary pattern was recorded by a 7-day food-frequency questionnaire. Results: 920 subjects were included (42% male, age 48±11, 23% body mass index ≥25kg/m and 5% diabetes). 263 (29%) had fatty liver; 60 (7%) had raised serum cytokeratin-18 fragment level (CK-18) suggestive of NASH; 27 of 887 (3%) subjects with reliable liver stiffness measurement had advanced fibrosis or cirrhosis. Compared with those without fatty liver, subjects with fatty liver had higher LBP (13.4±3.2mg/ml vs 11.4±2.7mg/ml; P < 0.001) and EndoCab IgG (228±247 GMU/ml vs 188±137 GMU/ml; P = 0.013) levels. Endotoxin markers also correlated positively with aminotransferases, IHTG, CK-18, insulin resistance and dyslipidaemia. Endotoxaemia was not associated with increased liver stiffness. Fetuin-A, the ligand linking fatty acid and Toll-like receptor 4, correlated with IHTG, insulin resistance and dyslipidaemia but did not have consistent association with endotoxaemia markers. Although total energy consumption and individual macronutrients were not associated with endotoxaemia, current drinkers (median alcohol consumption 20g/week [interquartile range 10–70 g]) had lower endotoxin, EndoCab IgG and fetuin-A levels than non-drinkers. Conclusions: Endotoxaemia is associated with fatty liver and possibly NASH in the general population. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of fatty liver and NASH in modest drinkers in previous observational studies. This study was supported by a grant from the Health and Medical Research Fund sponsored by the Hong Kong SAR Government [Ref CUHK-11120621]. P0981 ADAPTATION OF HEPATIC MITOCHONDRIAL FUNCTION IN OBESE HUMANS WITH OR WITHOUT NON-ALCOHOLIC STEATOHEPATITIS C. Koliaki, J. Szendroedi, K. Kaul, T. Jelenik, P. Nowotny, F. Jankowiak, C. Herder, M. Carstensen, M. Krausch, W. Trudo Knoefel, M. Schlensak, M. Roden. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Dusseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Dusseldorf, Germany; Department of Endocrinology and Diabetology, Heinrich Heine University, Dusseldorf, Germany; Institute of Pathology, Heinrich Heine University, Dusseldorf, Germany; Department of General, Visceral and Pediatric Surgery, Heinrich Heine University, Dusseldorf, Germany; General Surgery Department, St. Martinus Hospital, Dusseldorf, Germany, Dusseldorf, Germany E-mail: ckoliaki@yahoo.com