{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:34:21Z","timestamp":1791646461597,"version":"4.3.4"},"reference-count":51,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,12]],"date-time":"2023-02-12T00:00:00Z","timestamp":1676160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>The administration of an anticoagulant in patients with liver disease (nonalcoholic steatohepatitis\u2014NASH, nonalcoholic fatty liver disease\u2014NAFLD, chronic hepatitis, or cirrhosis) who have an indication (atrial fibrillation, venous thrombosis, or pulmonary embolism) is challenging because there is an imbalance between thrombosis and bleeding. There is a need to focus our attention on preventing risk factors because diabetes, obesity, dyslipidemia, smoking, and sedentary behavior are risk factors for both NASH\/NAFLD and AF, and these patients require anticoagulant treatment. Patients with advanced liver disease (Child\u2013Pugh C) were excluded from studies, so vitamin K antagonists (VKAs) are still recommended. Currently, VKAs are recommended for other conditions (antiphospholipid syndrome, mitral valve stenosis, and mechanical valve prosthesis). Amongst the patients under chronic anticoagulant treatment, especially for the elderly, bleeding as a result of the improper use of warfarin is one of the important causes of emergency admissions due to adverse reactions. DOACs are considered to be efficient and safe, with apixaban offering superior protection against stroke and a good safety profile as far as major bleeding is concerned compared to warfarin. DOACs are safe in the Child\u2013Pugh A and B classes (except rivaroxaban), and in the Child\u2013Pugh C class are contraindicated. Given that there are certain and reliable data for chronic kidney disease regarding the recommendations, in liver function impairment more randomized studies must be carried out, as the current data are still uncertain. In particular, DOACs have a simple administration, minimal medication interactions, a high safety and effectiveness profile, and now a reversal agent is available (for dabigatran and idarucizumab). Patients are also statistically more compliant and do not require INR monitoring.<\/jats:p>","DOI":"10.3390\/medicina59020346","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T03:07:57Z","timestamp":1676257677000},"page":"346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Oral Anticoagulation in Patients with Chronic Liver Disease"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0381-5550","authenticated-orcid":false,"given":"Raluca S.","family":"Costache","sequence":"first","affiliation":[{"name":"Internal Medicine and Gastroenterology Discipline, Carol Davila University of Medicine and Pharmacy, 7000 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea S.","family":"Dragomiric\u0103","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Carol Davila University Central Emergency Military Hospital, 7000 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan E.","family":"Gheorghe","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Carol Davila University Central Emergency Military Hospital, 7000 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3436-8041","authenticated-orcid":false,"given":"Vasile D.","family":"Balaban","sequence":"additional","affiliation":[{"name":"Internal Medicine and Gastroenterology Discipline, Carol Davila University of Medicine and Pharmacy, 7000 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silviu M.","family":"Stanciu","sequence":"additional","affiliation":[{"name":"Internal Medicine and Gastroenterology Discipline, Carol Davila University of Medicine and Pharmacy, 7000 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Jinga","sequence":"additional","affiliation":[{"name":"Internal Medicine and Gastroenterology Discipline, Carol Davila University of Medicine and Pharmacy, 7000 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-8654","authenticated-orcid":false,"given":"Daniel O.","family":"Costache","sequence":"additional","affiliation":[{"name":"Dermatology II Discipline, Carol Davila University of Medicine and Pharmacy, 7000 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,12]]},"reference":[{"key":"ref_1","first-page":"S67","article-title":"Exploring Indications for the Use of Direct Oral Anticoagulants","volume":"23","author":"Milling","year":"2017","journal-title":"Am. J. Manag. Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s11239-016-1446-0","article-title":"Vitamin K antagonists: Relative strengths and weaknesses vs. direct oral anticoagulants for stroke prevention in patients","volume":"43","author":"Zirlik","year":"2017","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6707985","DOI":"10.1155\/2022\/6707985","article-title":"Time Trends and Treatment Pathways in Prescribing Individual Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation: An Observational Study of More than Three Million Patients from Europe and the United States","volume":"2022","author":"Vora","year":"2022","journal-title":"Int. J. Clin. Pract."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3325\/cmj.2021.62.25","article-title":"Non-alcoholic fatty liver disease\u2014A procoagulant condition?","volume":"62","author":"Kukla","year":"2021","journal-title":"Croat. Med. J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yang, Y.J., Jung, M.H., Jeong, S.H., Hong, Y.P., Kim, Y.I., and An, S.J. (2020). The Association between Nonalcoholic Fatty Liver Disease and Stroke: Results from the Korean Genome and Epidemiology Study (KoGES). Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17249568"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1038\/s41598-021-83367-x","article-title":"Nonalcoholic fatty liver disease and the risk of atrial fibrillation stratified by body mass index: A nationwide population-based study","volume":"11","author":"Lee","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1136\/gut.52.3.404","article-title":"Thrombotic risk factors and extent of liver fibrosis in chronic viral hepatitis","volume":"52","author":"Papatheodoridis","year":"2003","journal-title":"Gut"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.jhepr.2019.02.006","article-title":"Anticoagulation in the cirrhotic patient","volume":"1","author":"Turco","year":"2019","journal-title":"JHEP Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1111\/jth.14836","article-title":"Anticoagulant therapy for splanchnic vein thrombosis: ISTH SSC Subcommittee Control of Anticoagulation","volume":"18","author":"Valeriani","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1016\/j.jacc.2018.03.023","article-title":"Oral Anticoagulation in Patients with Liver Disease","volume":"71","author":"Qamar","year":"2018","journal-title":"J. Am. Coll. Cardiol"},{"key":"ref_11","unstructured":"(2022, November 21). Oral Anticoagulants. Available online: https:\/\/www.amboss.com\/us\/knowledge\/Oral_anticoagulants."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/eurheartj\/ehaa612","article-title":"2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)","volume":"42","author":"Hindricks","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1177\/1060028019841582","article-title":"Direct oral anticoagulants in chronic liver disease","volume":"53","author":"Steuber","year":"2019","journal-title":"Ann. Pharmacother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S209","DOI":"10.1016\/j.dsx.2016.12.033","article-title":"Nonalcoholic fatty liver disease and the risk of clinical cardiovascular events: A systematic review and meta-analysis","volume":"11","author":"Mahfood","year":"2017","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e005307","DOI":"10.1161\/JAHA.116.005307","article-title":"Liver Cirrhosis in Patients With Atrial Fibrillation: Would Oral Anticoagulation Have a Net Clinical Benefit for Stroke Prevention?","volume":"6","author":"Kuo","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.18632\/oncotarget.22755","article-title":"Increased risk of cerebrovascular accident related to non-alcoholic fatty liver disease: A meta-analysis","volume":"9","author":"Hu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/hep.27546","article-title":"Groupe d\u2019Etude et de Traitement du Carcinome H\u00e9patocellulaire. Causes and consequences of portal vein thrombosis in 1,243 patients with cirrhosis: Results of a longitudinal study","volume":"61","author":"Nery","year":"2015","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1161\/CIRCOUTCOMES.113.000817","article-title":"Stratifying the risks of oral anticoagulation in patients with liver disease","volume":"7","author":"Efird","year":"2014","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.cgh.2012.01.012","article-title":"Efficacy and safety of anticoagulation on patients with cirrhosis and portal vein thrombosis","volume":"10","author":"Delgado","year":"2012","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106","DOI":"10.14740\/jocmr3669","article-title":"Bleeding Complications in Warfarin-Treated Patients Admitted to the Emergency Department","volume":"11","author":"Ozturk","year":"2019","journal-title":"J. Clin. Med. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1111\/jth.13780","article-title":"Bleeding-related hospital admissions and 30-day readmissions in patients with non-valvular atrial fibrillation treated with dabigatran versus warfarin","volume":"15","author":"Lau","year":"2017","journal-title":"J. Thromb. Haemost."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1002\/hep.28148","article-title":"Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial","volume":"63","author":"Bianchini","year":"2016","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1093\/eurheartj\/ehy136","article-title":"ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation","volume":"39","author":"Steffel","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.ahj.2015.07.006","article-title":"ROCKET AF Steering Committee and Investigators. Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: The Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF Trial)","volume":"170","author":"Bansilal","year":"2015","journal-title":"Am. Heart J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ahj.2009.07.035","article-title":"ARISTOTLE Investigators. Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: Design and rationale","volume":"159","author":"Lopes","year":"2010","journal-title":"Am. Heart J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.ahj.2009.02.005","article-title":"Rationale and design of RE-LY: Randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran","volume":"157","author":"Ezekowitz","year":"2009","journal-title":"Am. Heart J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.ahj.2010.06.042","article-title":"Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: Design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48)","volume":"160","author":"Ruff","year":"2010","journal-title":"Am. Heart J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.chest.2015.11.026","article-title":"Antithrombotic therapy for VTE disease: CHEST guideline and Expert Panel Report","volume":"149","author":"Kearon","year":"2016","journal-title":"Chest"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/hep.28906","article-title":"Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases","volume":"65","author":"Abraldes","year":"2017","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1053\/S0016-5085(21)03587-3","article-title":"AGA Clinical Practice Guideline on the Management of Coagulation Disorders in Patients With Cirrhosis","volume":"161","author":"Davitkov","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/hep.31646","article-title":"Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases","volume":"73","author":"Northup","year":"2020","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1001\/jama.2017.13883","article-title":"Association Between Use of Non\u2013Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation","volume":"318","author":"Chang","year":"2017","journal-title":"JAMA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3350\/cmh.2014.20.4.384","article-title":"Safety, efficacy, and response predictors of anticoagulation for the treatment of nonmalignant portal-vein thrombosis in patients with cirrhosis: A propensity score matching analysis","volume":"20","author":"Chung","year":"2014","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1007\/s12325-020-01307-z","article-title":"Direct Oral Anticoagulants in Patients with Liver Disease in the Era of Non-Alcoholic Fatty Liver Disease Global Epidemic: A Narrative Review","volume":"37","author":"Ballestri","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/hep.21231","article-title":"Elevated levels of von Willebrand Factor in cirrhosis support platelet adhesion despite reduced functional capacity","volume":"44","author":"Lisman","year":"2006","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1182\/blood.V81.3.720.720","article-title":"Degradation of von Willebrand factor in patients with acquired clinical conditions in which there is heightened proteolysis","volume":"81","author":"Federici","year":"1993","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/hep.21303","article-title":"Coagulation disorders and hemostasis in liver disease: Pathophysiology and critical assessment of current management","volume":"44","author":"Caldwell","year":"2006","journal-title":"Hepatology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1053\/j.gastro.2019.03.070","article-title":"AGA clinical practice update: Coagulation in cirrhosis","volume":"157","author":"Greenberg","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"18","DOI":"10.14309\/ajg.0000000000000486","article-title":"ACG Clinical Guideline: Disorders of the Hepatic and Mesenteric Circulation","volume":"115","author":"Simonetto","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.thromres.2018.08.011","article-title":"Direct oral anticoagulants in patients with liver cirrhosis: A systematic review","volume":"170","author":"Hoolwerf","year":"2018","journal-title":"Thromb. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1016\/j.jacc.2019.04.052","article-title":"Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Liver Disease","volume":"73","author":"Lee","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1136\/heartjnl-2013-305288","article-title":"Risk of drug-induced liver injury with the new oral anticoagulants: Systematic review and meta-analysis","volume":"100","author":"Caldeira","year":"2014","journal-title":"Heart"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s40264-015-0317-5","article-title":"Hepatotoxicity of New Oral Anticoagulants (NOACs)","volume":"38","author":"Liakoni","year":"2015","journal-title":"Drug Saf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1002\/hep.21907","article-title":"Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis","volume":"46","author":"Sanyal","year":"2007","journal-title":"Hepatology"},{"key":"ref_45","first-page":"10","article-title":"Anticoagulation in Patients With Chronic Liver Disease","volume":"17","author":"Gish","year":"2021","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1016\/S0140-6736(14)61685-8","article-title":"Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: A phase 3b, open-label, non-inferiority, randomized trial","volume":"385","author":"Goldstein","year":"2015","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1002\/hep.510290608","article-title":"Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: A meta-analysis","volume":"29","author":"Bernard","year":"1999","journal-title":"Hepatology"},{"key":"ref_48","first-page":"CD002907","article-title":"Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding","volume":"2","author":"Brezis","year":"2002","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/S0016-5085(03)00269-5","article-title":"Emergency sclerotherapy versus vasoactive drugs for variceal bleeding in cirrhosis: A Cochrane meta-analysis","volume":"124","author":"Pietrosi","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.3350\/cmh.2016.0110","article-title":"Anticoagulation in cirrhosis: A new paradigm?","volume":"23","author":"Leonardi","year":"2017","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s12325-015-0189-1","article-title":"Effect of rivaroxaban versus warfarin on health care costs among nonvalvular atrial fibrillation patients: Observations from rivaroxaban users and matched warfarin users","volume":"32","author":"Cloutier","year":"2015","journal-title":"Adv. Ther."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/2\/346\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:32:08Z","timestamp":1760121128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/2\/346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,12]]},"references-count":51,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["medicina59020346"],"URL":"https:\/\/doi.org\/10.3390\/medicina59020346","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,12]]}}}