title: Prothrombotic factors in histologically proven nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.
abstract: An independent role of nonalcoholic fatty liver disease (NAFLD) in the development of cardiovascular disease has been suggested, probably mediated through increased levels of prothrombotic factors. Therefore, we examined whether NAFLD is linked to a prothrombotic state, independently of metabolic risk factors in a large single-center cohort of overweight/obese patients. Patients presenting to the obesity clinic underwent a detailed metabolic and liver assessment, including an extensive panel of coagulation factors. If NAFLD was suspected, a liver biopsy was proposed. A series of 273 consecutive patients (65% female) with a liver biopsy were included (age, 44 ± 0.76 years; body mass index: 39.6 ± 0.40 kg/m(2)). Increase in fibrinogen, factor VIII, and von Willebrand factor and decrease in antithrombin III correlated with metabolic features, but not with liver histology. Levels of plasminogen activator inhibitor-1 (PAI-1) increased significantly with increasing severity of steatosis (P < 0.001), lobular inflammation (P < 0.001), ballooning (P = 0.002), and fibrosis (P < 0.001). Patients with nonalcoholic steatohepatitis had significantly higher PAI-1 values than those with normal liver (P < 0.001). In multiple regression, including anthropometric and metabolic parameters, steatosis remained an independent predictor of PAI-1 levels, explaining, together with fasting C-peptide and waist circumference, 21% of the variance in PAI-1. No consistent correlations with histology were found for the other coagulation factors.
  
  
  CONCLUSIONS
  In obesity, NAFLD severity independently contributes to the increase in PAI-1 levels, whereas other coagulation factors are unaltered. This finding might, in part, explain the increased cardiovascular risk associated with NAFLD.
authors.affiliation: Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Verrijken
authors.forename: Sven
authors.initials: S
authors.lastname: Francque
authors.forename: Ilse
authors.initials: I
authors.lastname: Mertens
authors.forename: Janne
authors.initials: J
authors.lastname: Prawitt
authors.forename: Sandrine
authors.initials: S
authors.lastname: Caron
authors.forename: Guy
authors.initials: G
authors.lastname: Hubens
authors.forename: Eric
authors.initials: E
authors.lastname: Van Marck
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Peter
authors.initials: P
authors.lastname: Michielsen
authors.forename: Luc
authors.initials: L
authors.lastname: Van Gaal
mesh_terms: D000328:Adult; D000886:Anthropometry; D001777:Blood Coagulation; D005234:Fatty Liver / Q000097:blood / Q000150:complications* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011446:Prospective Studies; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D013927:Thrombosis / Q000209:etiology*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human