title: Visceral fat: a key mediator of steatohepatitis in metabolic liver disease.
abstract: Visceral obesity is intimately associated with metabolic disease and adverse health outcomes. However, a direct association between increasing amounts of visceral fat and end-organ inflammation and scarring has not been demonstrated. We examined the association between visceral fat and liver inflammation in patients with nonalcoholic fatty liver disease (NAFLD) to delineate the importance of visceral fat to progressive steatohepatitis and hence the inflammatory pathogenesis of the metabolic syndrome. We undertook a cross-sectional, proof of concept study in 38 consecutive adults with NAFLD at a tertiary liver clinic. All subjects had a complete physical examination, anthropometric assessment, and fasting blood tests on the day of liver biopsy. Abdominal fat volumes were assessed by magnetic resonance imaging within 2 weeks of liver biopsy. The extent of hepatic inflammation and fibrosis augmented incrementally with increases in visceral fat (P < 0.01). For each 1% increase in visceral fat, the odds ratio for increasing liver inflammation and fibrosis was 2.4 (confidence interval [CI]: 1.3-4.2) and 3.5 (CI: 1.7-7.1), respectively. Visceral fat remained an independent predictor of advanced steatohepatitis (odds ratio [OR] 2.1, CI: 1.1-4.2, P = 0.05) and fibrosis (OR 2.9, CI: 1.4-6.3, P = 0.006) even when controlled for insulin resistance and hepatic steatosis. Interleukin-6 (IL-6) levels, which correlated with visceral fat, also independently predicted increasing liver inflammation. Visceral fat was associated with all components of the metabolic syndrome.
  
  
  CONCLUSIONS
  Visceral fat is directly associated with liver inflammation and fibrosis independent of insulin resistance and hepatic steatosis. Visceral fat should therefore be a central target for future interventions in nonalcoholic steatohepatitis and indeed all metabolic disease.
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, Australia. j.george@usyd.edu.au
authors.forename: David
authors.initials: D
authors.lastname: van der Poorten
authors.forename: Kerry-Lee
authors.initials: KL
authors.lastname: Milner
authors.forename: Jason
authors.initials: J
authors.lastname: Hui
authors.forename: Alexander
authors.initials: A
authors.lastname: Hodge
authors.forename: Michael I
authors.initials: MI
authors.lastname: Trenell
authors.forename: James G
authors.initials: JG
authors.lastname: Kench
authors.forename: Roslyn
authors.initials: R
authors.lastname: London
authors.forename: Tony
authors.initials: T
authors.lastname: Peduto
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Chisholm
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000005:Abdomen; D000328:Adult; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005234:Fatty Liver / Q000175:diagnosis*; D005260:Female; D006505:Hepatitis / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D050152:Intra-Abdominal Fat / Q000473:pathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology; D008875:Middle Aged; D011237:Predictive Value of Tests; D050151:Subcutaneous Fat / Q000473:pathology
chemical_list: D015850:Interleukin-6