title: Bacterial endotoxin and non-alcoholic fatty liver disease in the general population: a prospective cohort study.
abstract: BACKGROUND
  Patients with non-alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth.
  
  
  OBJECTIVE
  To test the hypothesis that endotoxemia is associated with non-alcoholic fatty liver disease (NAFLD) in the general population, and to study dietary factors associated with endotoxemia.
  
  
  METHODS
  Nine hundred and twenty adults were randomly selected from the government's census database and underwent proton-magnetic resonance spectroscopy to assess hepatic steatosis. Endotoxemia was assessed using the limulus amebocyte lysate, lipopolysaccharide-binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays.
  
  
  RESULTS
  Two hundred and sixty-three (29%) subjects had NAFLD. Subjects with NAFLD had slightly higher LBP (P < 0.001) and EndoCab IgG (P = 0.013) levels. EndoCab IgG remained an independent factor associated with intrahepatic triglycerides after adjusting for other metabolic factors. Among 565 subjects without NAFLD at baseline who had repeated assessment at a median interval of 47 months, 78 (13.8%) developed incident NAFLD and they also had higher LBP (P = 0.016). Moreover, LBP was associated with insulin resistance and dyslipidaemia, and modestly increased with the cytokeratin-18 fragment level but not liver stiffness measurement by transient elastography. Although total energy consumption and individual macronutrients were not associated with endotoxemia, current drinkers (mostly <140 g/week) had lower endotoxin, EndoCab IgG and fetuin-A levels than nondrinkers.
  
  
  CONCLUSIONS
  Endotoxin markers are associated with NAFLD in the general population, but do not have a major effect on NASH and fibrosis. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of NAFLD and NASH in modest drinkers in previous observational studies.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.|Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: V W-S
authors.initials: VW
authors.lastname: Wong
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.|Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: G L-H
authors.initials: GL
authors.lastname: Wong
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.|Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: H-Y
authors.initials: HY
authors.lastname: Chan
authors.affiliation: Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: D K-W
authors.initials: DK
authors.lastname: Yeung
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.|Centre for Nutritional Studies, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: R S-M
authors.initials: RS
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.|Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: A M-L
authors.initials: AM
authors.lastname: Chim
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.|Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: C K-M
authors.initials: CK
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.|Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Y-K
authors.initials: YK
authors.lastname: Tse
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.|Centre for Nutritional Studies, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: J
authors.initials: J
authors.lastname: Woo
authors.affiliation: Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.|Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: W C-W
authors.initials: WC
authors.lastname: Chu
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong.|Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.|State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: H L-Y
authors.initials: HL
authors.lastname: Chan
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D000428:Alcohol Drinking / Q000378:metabolism; D015415:Biomarkers; D002352:Carrier Proteins / Q000378:metabolism; D004032:Diet; D050171:Dyslipidemias / Q000378:metabolism; D019446:Endotoxemia / Q000453:epidemiology* / Q000503:physiopathology*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D007422:Intestines / Q000382:microbiology; D053538:Keratin-18 / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology* / Q000503:physiopathology*; D011446:Prospective Studies; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D002352:Carrier Proteins; D007074:Immunoglobulin G; D053538:Keratin-18; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein; C488421:KRT18 protein, human