Hemostatic dysfunction and thrombotic risk in metabolic dysfunction-associated steatotic liver disease.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic disorder with clinically relevant vascular and thrombotic consequences. Beyond hepatic steatosis, inflammation, and fibrosis, MASLD is associated with disturbances in hemostatic regulation that may shift the overall balance toward thrombosis. The prothrombotic phenotype of MASLD arises from the interaction of metabolic dysfunction, chronic inflammation, endothelial injury, platelet hyperreactivity, increased procoagulant activity, reduced natural anticoagulant capacity, and impaired fibrinolysis. These abnormalities may be detectable at early disease stages and appear to evolve with progression to steatohepatitis, advanced fibrosis, and cirrhosis. Epidemiological and clinical studies associate MASLD with venous thromboembolism, portal vein thrombosis, myocardial infarction, and ischemic stroke, with population-based data indicating approximately 1.8-fold higher venous thromboembolism risk and 3.4-fold higher PVT risk. However, conventional coagulation tests do not adequately reflect the net hemostatic balance, while candidate biomarkers and global hemostatic assays remain insufficiently validated for routine risk stratification. Hemostatic dysfunction in MASLD, particularly hypercoagulability, impaired fibrinolysis, endothelial dysfunction, and platelet activation, represents a clinically relevant but still underrecognized component of the disease. Clinical management should integrate liver disease stage, cardiometabolic burden, conventional thrombotic risk factors, and bleeding or procedural risk. Routine antiplatelet or anticoagulant therapy cannot currently be recommended solely on the basis of MASLD-related laboratory abnormalities.