{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T02:09:47Z","timestamp":1773367787095,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis, marked by rapid renal function decline and poor prognosis. Although clinical predictors of HRS outcomes have been extensively studied, less is known about how demographic factors influence mortality patterns. Methods: This analysis utilized CDC WONDER data to assess U.S. mortality trends for hepatorenal syndrome (HRS) in adults aged \u226525 years from 1999 to 2024. We calculated crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 100,000 and analyzed temporal trends using Joinpoint regression to determine the annual percentage change (APC) and average annual percentage change (AAPC). Results: From 1999 to 2024, 118,894 HRS-associated deaths were recorded. The overall AAMR decreased significantly from 2.43 in 1999 to 2.12 in 2024, with an AAPC of (AAPC \u22120.69% [95% CI: \u22120.90% to \u22120.51%]). Males consistently exhibited higher AAMRs than females (Males: 2.62 vs. Females: 1.63 in 2024). When stratified by race, the highest AAMR in 2024 was observed among non-Hispanic (NH) American Indian or Alaska Native populations (11.02), followed by Hispanic or Latino (2.58), NH White (2.23), NH Black or African American (1.30), and NH Asian or Pacific Islander populations (0.72). Regionally, the highest mortality was observed in the West, followed by the Midwest, South, and Northeast (2.88, 2.00, 1.92, and 1.53, respectively, in 2024). Rural areas (2.44) consistently exhibited higher AAMRs than urban areas (1.91) throughout the study period. Conclusions: HRS-related mortality has decreased modestly in the U.S over the last 26 years, yet significant inequities remain across population subgroups and regions. Mortality is disproportionately higher among males, NH American Indian or Alaska Native individuals, and residents of rural and western areas, highlighting the continued necessity for focused public health strategies.<\/jats:p>","DOI":"10.3390\/diseases14030106","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:12:24Z","timestamp":1773321144000},"page":"106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Trends and Demographics of Hepatorenal Syndrome-Related Mortality in the U.S., 1999\u20132024: A CDC WONDER Analysis"],"prefix":"10.3390","volume":"14","author":[{"given":"Syed Faisal","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Medicine, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Natche","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Medicine and Health Sciences, Basseterre KN0101, Saint Kitts and Nevis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7492-0826","authenticated-orcid":false,"given":"Mahendrakumar Achlaram","family":"Chaudhari","sequence":"additional","affiliation":[{"name":"Department of Medicine, Boston University, Boston, MA 02118, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0605-6965","authenticated-orcid":false,"given":"Hassan","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Al Nafees Medical College, Islamabad 44000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sammy","family":"Dawoud","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, International University of the Health Sciences, Basseterre KN0101, Saint Kitts and Nevis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hany","family":"Dawoud","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, International University of the Health Sciences, Basseterre KN0101, Saint Kitts and Nevis"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5274-4807","authenticated-orcid":false,"given":"Amna","family":"Shoaib","sequence":"additional","affiliation":[{"name":"Department of Medicine, Al Nafees Medical College, Islamabad 44000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hersh","family":"Tilokani","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harleen Kaur","family":"Chela","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Charleston Area Medical Center, West Virginia University, Charleston, WV 25302, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arsal","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Islamabad Medical & Dental College, Islamabad 44000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.jhep.2019.07.002","article-title":"News in pathophysiology, definition and classification of hepatorenal syndrome: A step beyond the International Club of Ascites (ICA) consensus document","volume":"71","author":"Angeli","year":"2019","journal-title":"J. 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