{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T16:00:31Z","timestamp":1793289631980,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","award":["2018-FA716E0930"],"award-info":[{"award-number":["2018-FA716E0930"]}],"id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hepatol Int"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background and aims<\/jats:title>\n                <jats:p>The cardiovascular hormones renin\/angiotensin\/aldosterone (RAA), brain-type natriuretic peptide (BNP)and arginine-vasopressin (AVP) are key regulators of systemic circulatory homeostasis in portal hypertension (PH). We assessed (i) the activation of renin, BNP and AVP across distinct stages of PH and (ii) whether activation of these hormones correlates with clinical outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Plasma levels of renin, proBNP and copeptin (AVP biomarker) were determined in 663 patients with advanced chronic liver disease (ACLD) undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital between 11\/2011 and 02\/2019. We stratified for Child stage (A\u2013C), HVPG (6\u20139 mmHg, 10\u201315 mmHg,\u2009\u2265\u200916 mmHg) and compensated vs. decompensated ACLD.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>With increasing PH, hyperdynamic state was indicated by higher heart rates (6\u20139 mmHg: median 71.0 [IQR 18.0] bpm, 10\u201315 mmHg: 76.0 [19.0] bpm,\u2009\u2265\u200916 mmHg: 80.0 [22.0] bpm; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), lower mean arterial pressure (6\u20139 mmHg: 103.0 [13.5] mmHg, 10\u201315 mmHg: 101.0 [19.5] mmHg,\u2009\u2265\u200916 mmHg: 99.0 [21.0] mmHg; <jats:italic>p<\/jats:italic>\u2009=\u20090.032) and lower serum sodium (6\u20139 mmHg: 139.0 [3.0] mmol\/L, 10\u201315 mmHg: 138.0 [4.0] mmol\/L,\u2009\u2265\u200916 mmHg: 138.0 [5.0] mmol\/L; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Across HVPG strata (6\u20139 mmHg vs. 10\u201315 mmHg vs\u2009\u2265\u200916 mmHg), median plasma levels of renin (21.0 [50.5] vs. 25.1 [70.9] vs. 65.4 [219.6] \u00b5IU\/mL; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), proBNP (86.1 [134.0] vs. 63.6 [118.0], vs. 132.2 [208.9] pg\/mL; <jats:italic>p<\/jats:italic>\u2009=\u20090.002) and copeptin (7.8 [7.7] vs. 5.6 [8.0] vs. 10.7 [18.6] pmol\/L; <jats:italic>p<\/jats:italic>\u2009=\u20090.024) increased with severity of PH. Elevated renin levels independently predicted first hepatic decompensation (adjusted hazard ratio [aHR]: 1.69; 95% confidence interval [95% CI] 1.07\u20132.68; <jats:italic>p<\/jats:italic>\u2009=\u20090.025) and mortality in compensated patients (aHR: 3.15; 95% CI 1.70\u20135.84; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and the overall cohort aHR: 1.42; 95% CI 1.01\u20132.01; <jats:italic>p<\/jats:italic>\u2009=\u20090.046). Elevated copeptin levels predicted mortality in decompensated patients (aHR: 5.77; 95% CI 1.27\u201326.33; <jats:italic>p<\/jats:italic>\u2009=\u20090.024) and in the overall cohort (aHR: 3.29; 95% CI 1.36\u20137.95; <jats:italic>p<\/jats:italic>\u2009=\u20090.008). ProBNP levels did not predict clinical outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The cardiovascular hormones renin, proBNP and AVP are activated with progression of ACLD and PH. Renin activation is a risk factor for hepatic decompensation and mortality, especially in compensated patients. Increased plasma copeptin is a risk factor for mortality, in particular in decompensated patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12072-021-10203-9","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T19:02:40Z","timestamp":1621623760000},"page":"1160-1173","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The differential activation of cardiovascular hormones across distinct stages of portal hypertension predicts clinical outcomes"],"prefix":"10.1007","volume":"15","author":[{"given":"Lukas","family":"Hartl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Jachs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Desbalmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Schaufler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Simbrunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Paternostro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schwabl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Josef Maria","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Semmler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Scheiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Bucsics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst","family":"Eigenbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrig","family":"Marculescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Szekeres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Peck-Radosavljevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kastl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-3583","authenticated-orcid":false,"given":"Thomas","family":"Reiberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"issue":"4","key":"10203_CR1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1159\/000456580","volume":"35","author":"IA Rowe","year":"2017","unstructured":"Rowe IA. 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B.Simbrunner received travel support from AbbVie and Gilead. P.S. received speaking honoraria from Bristol-Myers Squibb and Boehringer-Ingelheim, consulting fees from PharmaIN, and travel support from Falk. D.B. has received travel support from AbbVie and Gilead. B.Scheiner received travel support from Gilead, AbbVie and Ipsen. T.B. received travel support from AbbVie, Bristol-Myers Squibb, and Medis, as well as speaker fees from Bristol-Myers Squibb. M.P.-R. served as investigator for Abbott, Arqle-Daiichi, Bayer, BMS, Boehringer-Ingelheim, Gilead, Imclone, Ipsen, Novartis and Roche, as a speaker and\/or advisor for Abbott, Bayer, BMS, Boehringer-Ingelheim, Eisai, Gilead, Ipsen, MSD and Roche, received grant support from Abbott, Bayer, Gilead, MSD and Roche; data and safety monitoring board: BMS, Lilly-Imclone, ONXEO. M.T. received grant support from Albireo, Cymabay, Falk, Gilead, Intercept, MSD, and Takeda, honoraria for consulting from Albireo, Boehringer Ingelheim, BiomX, Falk, Genfit, Gilead, Intercept, MSD, Novartis, Phenex, and 3Regulus, speaker fees from Bristol-Myers Squibb, Falk, Gilead, Intercept and MSD, as well as travel support from AbbVie, FalkGilead and Intercept. M.M. served as a speaker and\/or consultant and\/or advisory board member for AbbVie, Bristol-Myers Squibb, Gilead, and W. L. Gore & Associates and received travel support from AbbVie, Bristol-Myers Squibb, and Gilead. T.R. received grant support from AbbVie, Boehringer-Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from AbbVie, Gilead, Gore, Intercept, Roche, MSD; consulting\/advisory board fee from AbbVie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; and travel support from Boehringer-Ingelheim, Gilead and Roche.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the ethics committee (EC) of the Medical University of Vienna (1493\/2016) and performed according to the current version of the Helsinki Declaration. Due to the retrospective design of the study the EC waived the need for informed consent.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}