{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:40:18Z","timestamp":1792176018652,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014468","name":"Mallinckrodt Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014468","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>Hepatorenal syndrome\u2010acute kidney injury (HRS\u2010AKI) is a life\u2010threatening complication of decompensated cirrhosis. The US Food and Drug Administration approved terlipressin use for HRS\u2010AKI based on the CONFIRM study, which demonstrated a significant improvement in HRS reversal with terlipressin versus placebo. The label notes elevated risk of respiratory failure in patients with volume overload or acute\u2010on\u2010chronic liver failure (ACLF) grade 3 and limited benefit when serum creatinine (SCr) exceeds 5\u2009mg\/dL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a post hoc analysis of CONFIRM excluding patients with ACLF grade 3 or SCr \u2265\u20095\u2009mg\/dL. This allowed us to assess the efficacy and safety of terlipressin in a population where the benefit\u2010to\u2010risk profile is more favourable. Efficacy outcomes included HRS reversal, renal replacement therapy (RRT), liver transplantation (LT), RRT\u2010free survival, LT\u2010free survival and overall survival. Changes in SCr, Model for End Stage Liver Disease (MELD) and sodium were also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HRS reversal occurred in 43% (60\/141) of patients with terlipressin versus 17% (13\/75) with placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Terlipressin was associated with significantly larger reductions (vs. placebo) in SCr (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and increases in serum sodium (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Importantly, LT rates were similar even though MELD scores decreased. 90\u2010day survival was similar between treatment arms. Notably, selecting patients with a favourable benefit\u2010to\u2010risk profile led to a similar incidence of respiratory failure between treatment arms (11% with terlipressin vs. 7% with placebo;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.360).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with HRS\u2010AKI without baseline ACLF grade 3 or SCr \u2265\u20095\u2009mg\/dL, terlipressin improved clinical outcomes and was not associated with an increased risk of respiratory failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      CONFIRM,\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT02770716\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70399","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T10:16:38Z","timestamp":1762510598000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Terlipressin for Hepatorenal Syndrome in Patients With Early\u2010Stage Acute\u2010on\u2010Chronic Liver Failure"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3751-2961","authenticated-orcid":false,"given":"Don C.","family":"Rockey","sequence":"first","affiliation":[{"name":"Digestive Disease Research Center Medical University of South Carolina  Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredric","family":"Gordon","sequence":"additional","affiliation":[{"name":"Tufts Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Thuluvath","sequence":"additional","affiliation":[{"name":"Mercy Medical Center and University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Victor","sequence":"additional","affiliation":[{"name":"Houston Methodist Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nyingi","family":"Kemmer","sequence":"additional","affiliation":[{"name":"Tampa General Medical Group  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanaz","family":"Cardoza","sequence":"additional","affiliation":[{"name":"Mallinckrodt Pharmaceuticals  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khurram","family":"Jamil","sequence":"additional","affiliation":[{"name":"Mallinckrodt Pharmaceuticals  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Todd","family":"Frederick","sequence":"additional","affiliation":[{"name":"California Pacific Medical Center  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0022-7"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840080532"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/17562848221102679"},{"issue":"9","key":"e_1_2_12_5_1","first-page":"1310","article-title":"Diagnosis, Prevention and Treatment of Hepatorenal Syndrome in Cirrhosis","volume":"56","author":"Salerno 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