{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T14:01:09Z","timestamp":1780754469047,"version":"3.54.1"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Hepatic edema indicates a poor prognosis and impaired quality of life in patients with cirrhosis. Tolvaptan is used in Japan to treat patients who do not respond to conventional diuretics. However, the long\u2010term prognostic effect of tolvaptan has not yet been fully determined in large\u2010scale, real\u2010world cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective multicenter study of patients with cirrhosis and hepatic edema who were treated with tolvaptan at 17 centers to identify the clinical predictors of treatment response and long\u2010term survival. An early response was defined as\n                      <jats:italic>a<\/jats:italic>\n                      \u2265\u00a01.5\u2010kg weight reduction within 7\u00a0days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 1165 patients, 58.8% showed an early response. In a multivariate analysis, blood urea nitrogen concentrations (BUN; per 1.0\u2010mg\/dL decrease), serum sodium concentrations (per 10\u2010mEq\/L increase), and the absence of hepatocellular carcinoma were independently associated with an early response. Early responders had longer overall survival than non\u2010responders (median, 15.3 vs. 7.7\u00a0months;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a02.70\u00a0\u00d7\u00a010\n                      <jats:sup>\u22126<\/jats:sup>\n                      ). An early response remained an independent factor associated with 5\u2010year survival (hazard ratio: 0.83;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a02.60\u00a0\u00d7\u00a010\n                      <jats:sup>\u22122<\/jats:sup>\n                      ) after adjustment for age, hepatic functional reserve, hepatocellular carcinoma, serum sodium concentrations, and BUN concentrations. Subgroup analyses of liver\u2010related mortality were consistent with the primary survival analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>An early response to tolvaptan, which is more likely to occur in patients without elevated BUN concentrations or hyponatremia, is independently associated with improved long\u2010term survival in patients with cirrhosis and hepatic edema. Our findings indicate the importance of initiating tolvaptan treatment before renal impairment or hyponatremia develops.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hepr.70140","type":"journal-article","created":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T12:51:00Z","timestamp":1770468660000},"page":"925-932","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Value of an Early Response to Tolvaptan and Its Clinical Implications in Patients With Cirrhosis and Hepatic Edema: A Nationwide Multicenter Cohort Study"],"prefix":"10.1111","volume":"56","author":[{"given":"Kaori","family":"Koyano","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5817-1845","authenticated-orcid":false,"given":"Taeang","family":"Arai","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1652-6168","authenticated-orcid":false,"given":"Hidenori","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Ogaki Municipal Hospital  Ogaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keizo","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Shinmatsudo Central General Hospital  Matsudo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joji","family":"Tani","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Neurology Faculty of Medicine Kagawa University  Kagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suguru","family":"Ogura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Mie University Graduate School of Medicine  Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Okubo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Nippon Medical School Chiba Hokusoh Hospital  Inzai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korenobu","family":"Hayama","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine Nippon Medical School  Tokyo 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