Preserved hemostatic status in patients with non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of thrombosis. However, it remains unclear if hypercoagulability contributes to this risk. We, therefore, determined an in-depth hemostatic profile in a cohort of well-defined patients with NAFLD. We drew blood samples from 68 patients with biopsy-proven NAFLD (simple steatosis n=24, NASH n=22, and NASH cirrhosis n=22), 30 lean controls, 30 overweight controls (body mass index (BMI) >25kg/m2), and 15 patients with alcoholic (ASH) cirrhosis, and performed in-depth hemostatic profiling. Basal and agonist-induced platelet activation, plasma levels of markers of platelet activation, and plasma levels of the platelet adhesion regulators von Willebrand factor and ADAMTS13 were comparable between patients with non-cirrhotic NAFLD and controls. Agonist-induced platelet activation was decreased in patients with cirrhosis. Thrombomodulin-modified thrombin generation was comparable between all patients and controls, although patients with cirrhosis had a reduced anticoagulant response to thrombomodulin. Thromboelastography test results were comparable between controls and non-cirrhotic NAFLD patients, but revealed moderate hypocoagulability in cirrhosis. Plasma fibrinolytic potential was decreased in overweight controls and non-cirrhotic NAFLD, but accelerated fibrinolysis was observed in ASH cirrhosis. Clot permeability was decreased in overweight controls and patients with NAFLD. The overall hemostatic profile is comparable between patients with non-cirrhotic NAFLD and controls. Additionally, pro-thrombotic features (hypofibrinolysis and a pro-thrombotic structure of fibrin clot) in patients with NAFLD are likely driven by obesity. Our study suggests a limited role for hyperactive hemostasis in the increased thrombotic risk in NAFLD. The combined results of this study show that the overall hemostatic status is comparable between healthy individuals and patients with a fatty liver disease.