{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:45:39Z","timestamp":1789083939017,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>The role of histamine in advanced chronic liver disease (ACLD) is poorly understood. We investigated plasma histamine levels across ACLD stages and their prognostic value.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included patients with evidence of ACLD, defined by portal hypertension (hepatic venous pressure gradient [HVPG] \u22656\u2009mmHg) and\/or a liver stiffness measurement by transient elastography \u226510\u2009kPa, who underwent HVPG measurement between 2017 and 2020. Acute\u2010on\u2010chronic liver failure (ACLF) and\/or liver\u2010related death were defined as composite endpoint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 251 patients, 82.5% had clinically significant portal hypertension (median HVPG: 17\u2009mmHg [interquartile range (IQR) 12\u201321]) and 135 patients (53.8%) were decompensated at baseline.<\/jats:p><jats:p>Median plasma histamine was 8.5\u2009nmol\/L (IQR: 6.4\u201311.5), 37.1% of patients showed elevated values (&gt;9.9\u2009nmol\/L). Histamine levels did not differ significantly across Child\u2010Turcotte\u2010Pugh (CTP) stages nor strata of model for end\u2010stage liver disease (MELD) or HVPG. Histamine levels correlated with markers of circulatory dysfunction (i.e. sodium, renin and aldosterone).<\/jats:p><jats:p>During a median follow\u2010up of 29.2\u2009months, 68 patients developed ACLF or liver\u2010related death. In univariate as well as in multivariate analysis (adjusting for age, sex, HVPG as well as either MELD, clinical stage, and serum albumin or CTP and serum sodium), elevated histamine levels remained associated with the composite endpoint. CTP\u2010based multivariate model adjusted sub\u2010distribution hazard ratio (asHR): 1.010 (95% CI: 1.004\u20131.021), <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001; MELD\u2010based multivariate model asHR: 1.030 (95% CI: 1.017\u20131.040), <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>High levels of histamine were linked to circulatory dysfunction in ACLD patients and independently associated with increased risks of ACLF or liver\u2010related death. Further mechanistic studies on the link between histamine signalling and development of hyperdynamic circulation and ACLF are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.16056","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T10:10:12Z","timestamp":1723543812000},"page":"2904-2914","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["High histamine levels are associated with acute\u2010on\u2010chronic liver failure and liver\u2010related death in patients with advanced chronic liver disease"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2587-1385","authenticated-orcid":false,"given":"Michael","family":"Schwarz","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-9146","authenticated-orcid":false,"given":"Benedikt","family":"Simbrunner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"},{"name":"CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences  Vienna Austria"},{"name":"Christian\u2010Doppler Laboratory for Portal Hypertension and Liver Fibrosis Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2871-4147","authenticated-orcid":false,"given":"Mathias","family":"Jachs","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3398-6120","authenticated-orcid":false,"given":"Lukas","family":"Hartl","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6708-3061","authenticated-orcid":false,"given":"Lorenz","family":"Balcar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-8518","authenticated-orcid":false,"given":"David J. 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