Impaired fibrinolysis without hypercoagulability characterises patients with non-alcoholic fatty liver disease

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Introduction: Cardiovascular disease is the major cause of mortality in non-alcoholic fatty liver disease (NAFLD), a disease affecting one quarter of the world's population. Coagulation imbalance may be a contributing factor but is yet to be convincingly disclosed. Aim: To perform an extensive mapping of the hemostatic system; primary and secondary hemostasis and the fibrinolytic system in non-diabetic NAFLD patients. Materials and methods: Twenty-five non-diabetic, biopsy-proven NAFLD patients [12 simple steatosis; 13 non-alcoholic steatohepatitis (NASH)] investigated by a comprehensive panel of coagulation and fibrinolysis tests in a cross-sectional study. Fifty age- and sex-matched healthy persons served as controls for each of the dynamic analyses: platelet aggregation, thrombin generation, fibrin formation and lysis. Body composition, insulin resistance makers, and liver fat assessed by proton density magnetic resonance imaging were measured in the patients. Results: Fibrinolytic function was impaired in simple steatosis [median 50% clot lysis time 1123 (min–max, 618–1967) s] and NASH [1448 (521–2618) s] compared to healthy controls [403 (184–1179) s] (p < 0.0001). Plasminogen activator inhibitor-1 (PAI-1) increased stepwise above reference interval from simple steatosis [54 (29–80) ng/ml] to NASH patients [109 (65–153) ng/ml; p = 0.03]. Impaired fibrinolysis correlated with hepatic fat fraction and insulin resistance; PAI-1 correlated with obesity and insulin resistance (ρ ≥ 0.42; p ≤ 0.04). Platelet aggregation, coagulation factors, natural anticoagulants, and thrombin generation were comparable to healthy controls and established reference intervals. Conclusions: NAFLD patients had impaired fibrinolysis without significant prothrombotic changes in coagulation. The impact of this abnormality on the increased cardiovascular risk remains to be investigated.

Original languageEnglish
Book seriesThrombosis Research
Volume213
Pages (from-to)9-15
Number of pages7
ISSN0049-3848
DOIs
Publication statusPublished - May 2022

    Research areas

  • Fibrinolysis, Non-alcoholic fatty liver disease, Plasminogen activator inhibitor-1, Platelet aggregation, Thrombin generation

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