{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T02:44:35Z","timestamp":1778899475538,"version":"3.51.4"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004721","name":"University of Tokyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000133","name":"Agency for Healthcare Research and Quality","doi-asserted-by":"publisher","award":["K08HS029195\u201001A"],"award-info":[{"award-number":["K08HS029195\u201001A"]}],"id":[{"id":"10.13039\/100000133","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["23HC2001"],"award-info":[{"award-number":["23HC2001"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JGH Open"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tolvaptan promotes electrolyte\u2010free water excretion and is widely used in Asia for ascites, but in Western countries its use is limited to hyponatremia because of hepatotoxicity concerns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a retrospective cohort study using the TriNetX Research Network, emulating a target trial of cirrhotic patients with hyponatremia in global regions. Patients receiving tolvaptan plus sodium supplementation were compared with those receiving sodium supplementation alone. The primary outcome was 30\u2010day all\u2010cause mortality; secondary outcomes included correction of hyponatremia, changes in liver and renal function, and initiation of hemodialysis. Survival was analyzed using Kaplan\u2013Meier curves with the log\u2010rank test and Cox proportional hazards models. Propensity score matching was applied to balance baseline covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 188\u2009707 eligible patients, 2130 received tolvaptan. After 1:1 matching, 1983 patients were analyzed in each group. Baseline characteristics were balanced, although serum sodium remained slightly lower in the tolvaptan group. Thirty\u2010day mortality was 14.4% in the tolvaptan group and 16.1% in the control group (HR 0.87, 95% CI 0.74\u20131.02; log\u2010rank\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.09). By the end of the follow\u2010up, serum sodium levels were significantly lower in the tolvaptan group. Changes in renal and liver function were comparable between groups, with no signal of excess hepatotoxicity. Rates of hemodialysis initiation did not differ significantly.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this large real\u2010world target trial emulation across global regions with ethnic diversity, in the context of longstanding safety concerns in cirrhosis, tolvaptan was not associated with excess short\u2010term mortality, with point estimates consistently favoring its use. Further studies are warranted to clarify its safety and effectiveness in diverse clinical settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jgh3.70395","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T06:28:04Z","timestamp":1775111284000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Real\u2010World Effectiveness of Tolvaptan for Hyponatremia in Cirrhosis Across Global Regions: A Target Trial Emulation"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9584-043X","authenticated-orcid":false,"given":"Kazuya","family":"Okushin","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Graduate School of Medicine, The University of Tokyo  Tokyo Japan"},{"name":"Department of Infection Control and Prevention Graduate School of Medicine, The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3021-2517","authenticated-orcid":false,"given":"Ryosuke","family":"Tateishi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Graduate School of Medicine, The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4074-1140","authenticated-orcid":false,"given":"Mitsuhiro","family":"Fujishiro","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Graduate School of Medicine, The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeya","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Prevention Graduate School of Medicine, The University of Tokyo  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiko","family":"Koike","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Graduate School of Medicine, The University of Tokyo  Tokyo Japan"},{"name":"Kanto Central Hospital  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6139-8444","authenticated-orcid":false,"given":"Tomohiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Iowa Carver College of Medicine  Iowa USA"},{"name":"Department of Health Management and Policy College of Public Health, University of Iowa  Iowa USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31884"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.03.024"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-021-01788-x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13678"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12098"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12822"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13337"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.41454"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14965"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-020-01727-2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205511"},{"key":"e_1_2_10_13_1","unstructured":"Food and Drug Administration Drug Safety Communication https:\/\/www.fda.gov\/drugs\/drug\u2010safety\u2010and\u2010availability\/fda\u2010drug\u2010safety\u2010communication\u2010fda\u2010limits\u2010duration\u2010and\u2010usage\u2010samsca\u2010tolvaptan\u2010due\u2010possible\u2010liver."},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab368"},{"key":"e_1_2_10_15_1","first-page":"e240","article-title":"2013 ACCF\/AHA Guideline for the Management of Heart Failure","volume":"128","author":"Yancy C. 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