title: Hepatic fat loss in advanced nonalcoholic steatohepatitis: are alterations in serum adiponectin the cause?
abstract: Advanced liver fibrosis in nonalcoholic steatohepatitis (NASH) is often accompanied by a reduction in hepatic fat to the point of complete fat loss (burnt-out NASH), but the mechanisms behind this phenomenon have not been elucidated. Adiponectin is raised in cirrhosis of any cause and has potent antisteatotic activity. In this study we examined 65 patients with advanced biopsy-proven NASH (fibrosis stage 3-4) and 54 with mild disease (fibrosis stage 0-1) to determine if disappearance of steatosis correlated with changes in serum adiponectin. All patents had fasting blood tests and anthropometric measures at the time of liver biopsy. Liver fat was accurately quantitated by morphometry. Serum adiponectin was measured by immunoassay. When compared to those with early disease, patients with advanced NASH were more insulin-resistant, viscerally obese, and older, but there was no difference in liver fat content or adiponectin levels. Adiponectin had a significant negative correlation with liver fat percentage in the whole cohort (r = -0.28, P < 0.01), driven by patients with advanced NASH (r = -0.40, P < 0.01). In advanced NASH, for each 4 μg/L increase in adiponectin there was an odds ratio OR of 2.0 (95% confidence interval [CI]: 1.3-3.0, P < 0.01) for a 5% reduction in hepatic fat. Adiponectin was highly and significantly associated with almost complete hepatic fat loss or burnt-out NASH (12.1 versus 7.4 μg/L, P = 0.001) on multivariate analysis. A relationship between adiponectin, bile acids, and adipocyte fexaramine activation was demonstrated in vivo and in vitro, suggestive of hepatocyte-adipocyte crosstalk.
  
  
  CONCLUSIONS
  Serum adiponectin levels in advanced NASH are independently associated with hepatic fat loss. Adiponectin may in part be responsible for the paradox of burnt-out NASH. (HEPATOLOGY 2012).
authors.affiliation: Storr Liver Unit, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Sydney, Australia. david.vanderpoorten@sydney.edu.au
authors.forename: David
authors.initials: D
authors.lastname: van der Poorten
authors.forename: Caroline F
authors.initials: CF
authors.lastname: Samer
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ramezani-Moghadam
authors.forename: Sally
authors.initials: S
authors.lastname: Coulter
authors.forename: Marina
authors.initials: M
authors.lastname: Kacevska
authors.forename: Dennis
authors.initials: D
authors.lastname: Schrijnders
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Wu
authors.forename: Duncan
authors.initials: D
authors.lastname: McLeod
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.forename: Mina
authors.initials: M
authors.lastname: Komuta
authors.forename: Tania
authors.initials: T
authors.lastname: Roskams
authors.forename: Christopher
authors.initials: C
authors.lastname: Liddle
authors.forename: Lionel
authors.initials: L
authors.lastname: Hebbard
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D001647:Bile Acids and Salts / Q000097:blood; D001706:Biopsy; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000097:blood*; D005260:Female; D005355:Fibrosis; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease
chemical_list: D052242:Adiponectin; D001647:Bile Acids and Salts