Prothrombotic factors in histologically proven nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Authors

  • An Verrijken,

    Corresponding author
    1. Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
    • Address reprint requests to: Luc Van Gaal, M.D., Ph.D., Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem (Antwerp), Belgium. E-mail: luc.van.gaal@uza.be; fax: +32-3-825.49.80.

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    • These authors contributed equally to this work.

  • Sven Francque,

    1. Department of Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
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    • These authors contributed equally to this work.

  • Ilse Mertens,

    1. Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
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  • Janne Prawitt,

    1. Université Lille Nord de France, INSERM U1011, UDSL, Institut Pasteur de Lille, Lille, France
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  • Sandrine Caron,

    1. Université Lille Nord de France, INSERM U1011, UDSL, Institut Pasteur de Lille, Lille, France
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  • Guy Hubens,

    1. Department of Abdominal Surgery, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
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  • Eric Van Marck,

    1. Department of Pathology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
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  • Bart Staels,

    1. Université Lille Nord de France, INSERM U1011, UDSL, Institut Pasteur de Lille, Lille, France
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  • Peter Michielsen,

    1. Department of Gastroenterology and Hepatology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
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  • Luc Van Gaal

    Corresponding author
    1. Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
    • Address reprint requests to: Luc Van Gaal, M.D., Ph.D., Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem (Antwerp), Belgium. E-mail: luc.van.gaal@uza.be; fax: +32-3-825.49.80.

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  • See Editorial on Page 16

    Potential conflict of interest: Nothing to report.

  • This work is part of the project “Hepatic and adipose tissue and functions in the metabolic syndrome” (HEPADIP), which is supported by the European Commission as an Integrated Project under the 6th Framework Program (contract LSHM-CT-2005-018734).

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/m2). 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. Conclusion: 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. (Hepatology 2014;58:121–129)

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