Nonalcoholic Fatty Liver Disease, Portal Vein Thrombosis and Coagulation: More Questions Than Answers?
Making the distinction between NASH and being overweight or obese and the impact of each on clinically relevant hemostatic events is important given recent conflicting reports on hemostatic profiles in these patient populations.3,4 Tripodi et al3 argue that nonalcoholic fatty liver disease (NAFLD) is the main prohemostatic factor as supported by a progressive procoagulation imbalance from steatosis to cirrhosis in which both the endogenous thrombin potential (ETP) ratio and Factor VIII:Protein C ratio increase. On the other hand, based on analysis of not only coagulation but also primary hemostasis and fibrinolysis, Potze et al4 concluded that overall, hemostasis remains rebalanced in patients with NAFLD and that being overweight conferred a much greater prohemostatic profile. Nonetheless, Potze et al4 identified several individual prohemostatic features in patients with NAFLD or NASH cirrhosis including elevated levels of plasminogen activator inhibitor 1, fibrinogen, factor VIII and decreased levels of antithrombin. Furthermore, NAFLD subjects were found to have both evidence of hypofibrinolysis as well as a prohemostatic structure to the fibrinclot with increased clot density and decreased clot permeability, the latter of which was also seen in overweight patients without NAFLD.
Given these opposite conclusions about the complex interplay between NAFLD, obesity and clotting risk, the hemostatic environment in patients with NAFLD and NASH cirrhosis remains controversial and offers avenue for future mechanistic study. What does appear to hold true based on large-scale epidemiologic data is that patients with NAFLD are at increased risk for clinically important thrombotic events including PVT, as well as pulmonary embolism and deep vein thrombosis.1,2,5 The hemostatic environment remains relatively unexplored in this patient population, and we would suggest this as an avenue for future provocative study and ultimately the possibility of intervention with anticoagulation pretransplantation and posttransplantation in this high-risk population where PVT may be more of a disease modifier rather than downstream effect.