Direct Oral Anticoagulants in Patients with Liver Disease in the Era of Non-Alcoholic Fatty Liver Disease Global Epidemic: A Narrative Review

Abstract

Atrial fibrillation (AF) and venous thromboembolism (VTE) are highly prevalent and relevant healthcare issues. Direct oral anticoagulants (DOACs) are now the first-choice for anticoagulant treatment of these conditions displaying a better efficacy/safety profile than vitamin-K antagonists, mainly due to significantly reduced risk of major bleeding, especially of intracranial haemorrhage. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries showing a continuously growing prevalence. Nonalcoholic steatohepatitis (NASH), its evolutive form, will be the leading cause for liver transplantation by 2020. NAFLD is independently associated with an increased risk of abnormalities of cardiac structure and function, including cardiac rhythm disorders (mainly AF). Moreover, data suggest an increased risk of unprovoked VTE associated with NAFLD/NASH. Therefore, a growing number of patients with chronic liver disease (CLD) will be candidate for anticoagulant therapy in the near future. Cirrhosis of any etiology is characterized by an unstable thrombosis/bleeding haemostatic balance, making anticoagulant therapy particularly challenging in this condition. Given that patients with significant active liver disease and cirrhosis were excluded from all pivotal randomized controlled trials on DOACs, this comprehensive review aims at critically discussing real-world evidence, including the latest population studies, regarding the use of DOACs in patients with CLD/cirrhosis.

Keywords: Atrial fibrillation; Cardiovascular disease; Cirrhosis; Direct oral anticoagulants; Fatty liver; Heparin; Liver disease; Stroke; Thrombosis; Warfarin.

Fig. 1

Balance between thrombosis and bleeding in liver disease. ADAMTS13 ADAM metallopeptidase with thrombospondin type 1 motif 13, PAI plasminogen activator inhibitor, TAFI thrombin-activatable fibrinolysis inhibitor, TFPI tissue factor pathway inhibitor

Fig. 2

Management of anticoagulation in patient with CLD/cirrhosis. a DOACs initiation. AC anticoagulation, CTP Child Turcotte-Pugh, DOACs direct oral anticoagulants, EGD esophagogastroduodenoscopy, EVL endoscopic variceal ligation, INR international normalized ratio, NSBBs non-selective beta-blockers, RWS red wale signs. *can be used. b Management of bleeding complications. DOACs direct oral anticoagulants, EVL endoscopic variceal ligation, HRS hepatorenal syndrome, 4F-PCC four factor-prothrombin complex concentrate, RBC red blood cells, TIPS transjugular intrahepatic portosystemic shunt