Hypercoagulability in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD): Causes and Consequences

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is anticipated that it could become even more prevalent in parallel with an increase in the incidence of metabolic diseases closely related to NAFLD, such as obesity, type II diabetes, dyslipidemia, and arterial hypertension. In addition to liver impairment, NAFLD is associated with cardiovascular diseases. Fibrosis, atherosclerosis, and venous thrombosis are basically the pathogenic mechanisms behind these clinical manifestations, and all are plausibly associated with hypercoagulability that may, in turn, develop because of an imbalance of pro- vs. anticoagulants and the presence of such procoagulant molecular species as microvesicles, neutrophil extracellular traps (NETs), and inflammation. The assessment of hypercoagulability by means of thrombin generation is a global procedure that mimics the coagulation process occurring in vivo much better than any other coagulation test, and is considered to be the best candidate laboratory tool for assessing, with a single procedure, the balance of coagulation in NAFLD. In addition to defining the state of hypercoagulability, the assessment of thrombin generation could also be used to investigate, in clinical trials, the best approach (therapeutic and/or lifestyle changes) for minimizing hypercoagulability and, hence, the risk of cardiovascular diseases, progression to atherosclerosis, and liver fibrosis in patients with NAFLD.

Keywords

• procoagulant imbalance
• thrombin generation
• antithrombin
• protein C
• factor VIII
• thrombomodulin