Direct oral anticoagulants in liver cirrhosis: rationale and current evidence

Liver cirrhosis (LC) is a major health concern worldwide with a complex pathophysiology affecting various biological systems, including all aspects of haemostasis. Bleeding risk is mainly driven by portal hypertension, but in end-stage liver disease it is further increased by alterations in haemostatic components, including platelet functions, coagulation, and fibrinolysis. Concurrently, patients with LC are prone to venous thromboembolic events (VTE) because of the altered haemostatic balance, in particular an increase in thrombin generation. In patients with LC, vitamin K antagonists (VKA) and low molecular weight heparins (LMWH) are currently the standard of care for VTE prevention and VKA for prevention of stroke in case of atrial fibrillation. However, direct oral anticoagulants (DOAC) appear promising in this patient population, with specific advantages. Clinical experience suggests that DOAC are a safe and possibly more effective alternative to traditional anticoagulants for the treatment of VTE in patients with compensated LC. In addition, emerging data suggest that primary prophylactic treatment with anticoagulants may improve clinical outcome of patients with LC by reducing the risk of liver decompensation. The selection of the most appropriate DOAC remains to be clarified. This review focuses on the rationale for the use of DOAC in patients with LC, the specific effects of the different DOAC as assessed by in vitro and in vivo pharmacokinetic and pharmacodynamic studies, as well as the clinical outcomes of patients with LC on DOAC.