{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:45:41Z","timestamp":1791773141215,"version":"4.3.4"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:00:00Z","timestamp":1715385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Portal vein thrombosis (PVT) worsens the long-term prognosis of patients with cirrhosis; however, the optimal treatment remains to be determined. Reports on the efficacy of direct oral anticoagulants are increasing, and further evidence is needed. Therefore, we investigated the effectiveness of treatment with edoxaban in patients with PVT. We retrospectively reviewed the outcomes of edoxaban and warfarin as antithrombotic therapies for PVT. The median overall survival time was 4.2\u00a0years in patients with PVT, with a 1-year survival rate of 70.7% and a 5-year survival rate of 47.9%. The leading cause of death was hepatocellular carcinoma. The overall response rate for thrombolysis in the edoxaban group was 76.7% compared to 29.4% in the warfarin group, and edoxaban significantly improved PVT compared to warfarin. In addition, edoxaban provided long-term improvement of PVT. Warfarin, on the other hand, was temporarily effective but did not provide long-term benefits. The Child\u2013Pugh and albumin-bilirubin scores did not change after edoxaban or warfarin use. No deaths occurred due to adverse events associated with edoxaban or warfarin. Edoxaban as a single agent can achieve long-term recanalization without compromising the hepatic reserves. Edoxaban is easy to initiate, even in an outpatient setting, and could become a major therapeutic agent for the treatment of PVT.<\/jats:p>","DOI":"10.1038\/s41598-024-60235-y","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T05:13:23Z","timestamp":1715404403000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Effectiveness of edoxaban in portal vein thrombosis associated with liver cirrhosis"],"prefix":"10.1038","volume":"14","author":[{"given":"Tomoko","family":"Tadokoro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joji","family":"Tani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takushi","family":"Manabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Takuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Nakahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Oura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shima","family":"Mimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asahiro","family":"Morishita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Kobara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Himoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Ono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Masaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"key":"60235_CR1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.jhep.2011.12.034","volume":"57","author":"C Francoz","year":"2012","unstructured":"Francoz, C., Valla, D. & Durand, F. Portal vein thrombosis, cirrhosis, and liver transplantation. J. Hepatol. 57, 203\u2013212. https:\/\/doi.org\/10.1016\/j.jhep.2011.12.034 (2012).","journal-title":"J. Hepatol."},{"key":"60235_CR2","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1111\/j.1365-2036.2009.04182.x","volume":"31","author":"EA Tsochatzis","year":"2010","unstructured":"Tsochatzis, E. A., Senzolo, M., Germani, G., Gatt, A. & Burroughs, A. K. Systematic review: Portal vein thrombosis in cirrhosis. Aliment Pharmacol. Ther. 31, 366\u2013374. https:\/\/doi.org\/10.1111\/j.1365-2036.2009.04182.x (2010).","journal-title":"Aliment Pharmacol. Ther."},{"key":"60235_CR3","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1111\/hepr.13614","volume":"51","author":"H Yoshida","year":"2021","unstructured":"Yoshida, H., Shimizu, T., Yoshioka, M. & Taniai, N. Management of portal hypertension based on portal hemodynamics. Hepatol. Res. 51, 251\u2013262. https:\/\/doi.org\/10.1111\/hepr.13614 (2021).","journal-title":"Hepatol. Res."},{"key":"60235_CR4","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/ijms22158139","volume":"22","author":"T Tadokoro","year":"2021","unstructured":"Tadokoro, T., Morishita, A. & Masaki, T. Diagnosis and therapeutic management of liver fibrosis by MicroRNA. Int. J. Mol. Sci. 22, 15. https:\/\/doi.org\/10.3390\/ijms22158139 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"60235_CR5","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1016\/j.jhep.2004.01.001","volume":"40","author":"L Amitrano","year":"2004","unstructured":"Amitrano, L. et al. Risk factors and clinical presentation of portal vein thrombosis in patients with liver cirrhosis. J. Hepatol. 40, 736\u2013741. https:\/\/doi.org\/10.1016\/j.jhep.2004.01.001 (2004).","journal-title":"J. Hepatol."},{"key":"60235_CR6","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1055\/s-2002-32122","volume":"40","author":"R Gunther","year":"2002","unstructured":"Gunther, R. & Folsch, U. R. High plasma levels of factor VIII and von Willebrand factor in a patient with portal vein thrombosis. Z. Gastroenterol. 40, 409\u2013412. https:\/\/doi.org\/10.1055\/s-2002-32122 (2002).","journal-title":"Z. Gastroenterol."},{"key":"60235_CR7","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.jhep.2015.07.040","volume":"64","author":"European Association for the Study of the Liver","year":"2016","unstructured":"European Association for the Study of the Liver. Electronic address, e. e. e. EASL Clinical Practice Guidelines: Vascular diseases of the liver. J. Hepatol. 64, 179\u2013202. https:\/\/doi.org\/10.1016\/j.jhep.2015.07.040 (2016).","journal-title":"J. Hepatol."},{"key":"60235_CR8","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/s00535-021-01788-x","volume":"56","author":"H Yoshiji","year":"2021","unstructured":"Yoshiji, H. et al. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J. Gastroenterol. 56, 593\u2013619. https:\/\/doi.org\/10.1007\/s00535-021-01788-x (2021).","journal-title":"J. Gastroenterol."},{"key":"60235_CR9","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/hepr.13840","volume":"53","author":"K Hayama","year":"2023","unstructured":"Hayama, K. et al. Clinical outcomes of antithrombin III-based therapy for patients with portal vein thrombosis: A retrospective, multicenter study. Hepatol. Res. 53, 51\u201360. https:\/\/doi.org\/10.1111\/hepr.13840 (2023).","journal-title":"Hepatol. Res."},{"key":"60235_CR10","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1186\/s12876-019-1140-8","volume":"19","author":"T Hayashi","year":"2019","unstructured":"Hayashi, T. et al. Danaparoid sodium-based anticoagulation therapy for portal vein thrombosis in cirrhosis patients. BMC Gastroenterol. 19, 217. https:\/\/doi.org\/10.1186\/s12876-019-1140-8 (2019).","journal-title":"BMC Gastroenterol."},{"key":"60235_CR11","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.dld.2021.07.039","volume":"54","author":"JH Koh","year":"2022","unstructured":"Koh, J. H. et al. Efficacy and safety of direct oral anticoagulants versus vitamin K antagonist for portal vein thrombosis in cirrhosis: A systematic review and meta-analysis. Dig. Liver Dis. 54, 56\u201362. https:\/\/doi.org\/10.1016\/j.dld.2021.07.039 (2022).","journal-title":"Dig. Liver Dis."},{"key":"60235_CR12","doi-asserted-by":"publisher","first-page":"e018917","DOI":"10.1161\/JAHA.120.018917","volume":"9","author":"E Campello","year":"2020","unstructured":"Campello, E. et al. Direct oral anticoagulants in patients with inherited thrombophilia and venous thromboembolism: A prospective cohort study. J. Am. Heart Assoc. 9, e018917. https:\/\/doi.org\/10.1161\/JAHA.120.018917 (2020).","journal-title":"J. Am. Heart Assoc."},{"key":"60235_CR13","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1111\/j.1538-7836.2008.03064.x","volume":"6","author":"T Furugohri","year":"2008","unstructured":"Furugohri, T. et al. DU-176b, a potent and orally active factor Xa inhibitor: In vitro and in vivo pharmacological profiles. J. Thromb. Haemost. 6, 1542\u20131549. https:\/\/doi.org\/10.1111\/j.1538-7836.2008.03064.x (2008).","journal-title":"J. Thromb. Haemost."},{"key":"60235_CR14","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1177\/0091270009351883","volume":"50","author":"K Ogata","year":"2010","unstructured":"Ogata, K. et al. Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J. Clin. Pharmacol. 50, 743\u2013753. https:\/\/doi.org\/10.1177\/0091270009351883 (2010).","journal-title":"J. Clin. Pharmacol."},{"key":"60235_CR15","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1002\/cpdd.53","volume":"2","author":"N Matsushima","year":"2013","unstructured":"Matsushima, N., Lee, F., Sato, T., Weiss, D. & Mendell, J. Bioavailability and safety of the factor Xa inhibitor edoxaban and the effects of quinidine in healthy subjects. Clin. Pharmacol. Drug. Dev. 2, 358\u2013366. https:\/\/doi.org\/10.1002\/cpdd.53 (2013).","journal-title":"Clin. Pharmacol. Drug. Dev."},{"key":"60235_CR16","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1002\/jcph.550","volume":"55","author":"J Mendell","year":"2015","unstructured":"Mendell, J., Johnson, L. & Chen, S. An open-label, phase 1 study to evaluate the effects of hepatic impairment on edoxaban pharmacokinetics and pharmacodynamics. J. Clin. Pharmacol. 55, 1395\u20131405. https:\/\/doi.org\/10.1002\/jcph.550 (2015).","journal-title":"J. Clin. Pharmacol."},{"key":"60235_CR17","doi-asserted-by":"publisher","first-page":"2736","DOI":"10.1161\/CIRCULATIONAHA.110.009449","volume":"123","author":"R Mehran","year":"2011","unstructured":"Mehran, R. et al. Standardized bleeding definitions for cardiovascular clinical trials: A consensus report from the Bleeding Academic Research Consortium. Circulation 123, 2736\u20132747. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.110.009449 (2011).","journal-title":"Circulation"},{"key":"60235_CR18","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12916-018-1069-8","volume":"16","author":"X Qi","year":"2018","unstructured":"Qi, X. et al. Transient portal vein thrombosis in liver cirrhosis. BMC Med. 16, 83. https:\/\/doi.org\/10.1186\/s12916-018-1069-8 (2018).","journal-title":"BMC Med."},{"key":"60235_CR19","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/hepr.13725","volume":"52","author":"S Yokoyama","year":"2022","unstructured":"Yokoyama, S. et al. Absence of large portal collateral vessels is associated with spontaneous improvement of cirrhotic portal vein thrombosis. Hepatol. Res. 52, 199\u2013209. https:\/\/doi.org\/10.1111\/hepr.13725 (2022).","journal-title":"Hepatol. Res."},{"key":"60235_CR20","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s12876-017-0668-8","volume":"17","author":"S Fujiyama","year":"2017","unstructured":"Fujiyama, S. et al. Portal vein thrombosis in liver cirrhosis: Incidence, management, and outcome. BMC Gastroenterol. 17, 112. https:\/\/doi.org\/10.1186\/s12876-017-0668-8 (2017).","journal-title":"BMC Gastroenterol."},{"key":"60235_CR21","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13942","author":"A Sato","year":"2023","unstructured":"Sato, A. et al. Anticoagulation against portal vein thrombosis reduces mortality and liver cirrhosis-related complications: A propensity score-matched study. Hepatol. Res. https:\/\/doi.org\/10.1111\/hepr.13942 (2023).","journal-title":"Hepatol. Res."},{"key":"60235_CR22","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s12325-020-01550-4","volume":"38","author":"L Wang","year":"2021","unstructured":"Wang, L. et al. Anticoagulation favors thrombus recanalization and survival in patients with liver cirrhosis and portal vein thrombosis: Results of a meta-analysis. Adv. Ther. 38, 495\u2013520. https:\/\/doi.org\/10.1007\/s12325-020-01550-4 (2021).","journal-title":"Adv. Ther."},{"key":"60235_CR23","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1056\/NEJMra1011170","volume":"365","author":"A Tripodi","year":"2011","unstructured":"Tripodi, A. & Mannucci, P. M. The coagulopathy of chronic liver disease. N. Engl. J. Med. 365, 147\u2013156. https:\/\/doi.org\/10.1056\/NEJMra1011170 (2011).","journal-title":"N. Engl. J. Med."},{"key":"60235_CR24","doi-asserted-by":"publisher","first-page":"E107","DOI":"10.1111\/hepr.12934","volume":"48","author":"H Hidaka","year":"2018","unstructured":"Hidaka, H. et al. Antithrombin III for portal vein thrombosis in patients with liver disease: A randomized, double-blind, controlled trial. Hepatol. Res. 48, E107\u2013E116. https:\/\/doi.org\/10.1111\/hepr.12934 (2018).","journal-title":"Hepatol. Res."},{"key":"60235_CR25","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1002\/hep.22772","volume":"49","author":"LD DeLeve","year":"2009","unstructured":"DeLeve, L. D., Valla, D. C., Garcia-Tsao, G., American Association for the Study Liver, D. Vascular disorders of the liver. Hepatology 49, 1729\u20131764. https:\/\/doi.org\/10.1002\/hep.22772 (2009).","journal-title":"Hepatology"},{"key":"60235_CR26","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1056\/NEJMoa1306638","volume":"369","author":"VTEI Hokusai","year":"2013","unstructured":"Hokusai, V. T. E. I. et al. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N. Engl. J. Med. 369, 1406\u20131415. https:\/\/doi.org\/10.1056\/NEJMoa1306638 (2013).","journal-title":"N. Engl. J. Med."},{"key":"60235_CR27","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1056\/NEJMoa1310907","volume":"369","author":"RP Giugliano","year":"2013","unstructured":"Giugliano, R. P. et al. Edoxaban versus warfarin in patients with atrial fibrillation. N. Engl. J. Med. 369, 2093\u20132104. https:\/\/doi.org\/10.1056\/NEJMoa1310907 (2013).","journal-title":"N. Engl. J. Med."},{"key":"60235_CR28","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1111\/bcp.12054","volume":"76","author":"D Kubitza","year":"2013","unstructured":"Kubitza, D. et al. Effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of a single dose of rivaroxaban, an oral, direct Factor Xa inhibitor. Br. J. Clin. Pharmacol. 76, 89\u201398. https:\/\/doi.org\/10.1111\/bcp.12054 (2013).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"60235_CR29","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/hepr.12895","volume":"48","author":"Y Nagaoki","year":"2018","unstructured":"Nagaoki, Y. et al. Efficacy and safety of edoxaban for treatment of portal vein thrombosis following danaparoid sodium in patients with liver cirrhosis. Hepatol. Res. 48, 51\u201358. https:\/\/doi.org\/10.1111\/hepr.12895 (2018).","journal-title":"Hepatol. Res."},{"key":"60235_CR30","doi-asserted-by":"publisher","first-page":"e003998","DOI":"10.1161\/CIRCOUTCOMES.117.003998","volume":"11","author":"J Aisenberg","year":"2018","unstructured":"Aisenberg, J. et al. Gastrointestinal bleeding with edoxaban versus warfarin: Results from the ENGAGE AF-TIMI 48 trial (effective anticoagulation with factor xa next generation in atrial fibrillation-thrombolysis in myocardial infarction). Circ. Cardiovasc. Qual. Outcomes 11, e003998. https:\/\/doi.org\/10.1161\/CIRCOUTCOMES.117.003998 (2018).","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"60235_CR31","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1186\/s40792-020-01086-3","volume":"6","author":"H Iida","year":"2020","unstructured":"Iida, H. et al. Cerebellar hemorrhage in patients treated with edoxaban for portal vein thrombosis after hepatobiliary surgery: A report of two cases. Surg. Case Rep. 6, 319. https:\/\/doi.org\/10.1186\/s40792-020-01086-3 (2020).","journal-title":"Surg. Case Rep."},{"key":"60235_CR32","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3390\/cancers15061834","volume":"15","author":"K Oura","year":"2023","unstructured":"Oura, K. et al. Prognostic value of skeletal muscle loss in patients with hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy. Cancers (Basel) 15, 6. https:\/\/doi.org\/10.3390\/cancers15061834 (2023).","journal-title":"Cancers (Basel)"},{"key":"60235_CR33","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/diagnostics13071245","volume":"13","author":"T Manabe","year":"2023","unstructured":"Manabe, T. et al. Usefulness of the measurement of psoas muscle volume for sarcopenia diagnosis in patients with liver disease. Diagnostics (Basel) 13, 7. https:\/\/doi.org\/10.3390\/diagnostics13071245 (2023).","journal-title":"Diagnostics (Basel)"},{"key":"60235_CR34","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1200\/JCO.2014.57.9151","volume":"33","author":"PJ Johnson","year":"2015","unstructured":"Johnson, P. J. et al. Assessment of liver function in patients with hepatocellular carcinoma: A new evidence-based approach-the ALBI grade. J. Clin. Oncol 33, 550\u2013558. https:\/\/doi.org\/10.1200\/JCO.2014.57.9151 (2015).","journal-title":"J. Clin. Oncol"},{"key":"60235_CR35","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1159\/000479984","volume":"6","author":"A Hiraoka","year":"2017","unstructured":"Hiraoka, A. et al. Validation and potential of albumin-bilirubin grade and prognostication in a nationwide survey of 46,681 hepatocellular carcinoma patients in Japan: The need for a more detailed evaluation of hepatic function. Liver Cancer 6, 325\u2013336. https:\/\/doi.org\/10.1159\/000479984 (2017).","journal-title":"Liver Cancer"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-60235-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-60235-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-60235-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T05:18:03Z","timestamp":1715404683000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-60235-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,11]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["60235"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-60235-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3345017\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,11]]},"assertion":[{"value":"11 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10784"}}