{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:35:26Z","timestamp":1760236526500,"version":"build-2065373602"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Scientific Fund of the Mayor of the City of Vienna","award":["MA 40-GMWF-485569-2020"],"award-info":[{"award-number":["MA 40-GMWF-485569-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>(1) Background: Cirrhotic patients have an increased risk for severe COVID-19. We investigated the renin-angiotensin-aldosterone system (RAS), parameters of endothelial dysfunction, inflammation, and coagulation\/fibrinolysis in cirrhotic patients and in COVID-19 patients. (2) Methods: 127 prospectively characterized cirrhotic patients (CIRR), along with nine patients with mild COVID-19 (mild-COVID), 11 patients with COVID-19 acute respiratory distress syndrome (ARDS; ARDS-COVID), and 10 healthy subjects (HS) were included in the study. Portal hypertension (PH) in cirrhotic patients was characterized by hepatic venous pressure gradient (HVPG). (3) Results: With increased liver disease severity (Child\u2212Pugh stage A vs. B vs. C) and compared to HS, CIRR patients exhibited higher RAS activity (angiotensin-converting enzyme (ACE), renin, aldosterone), endothelial dysfunction (von Willebrand-factor (VWF) antigen), inflammation (C-reactive protein (CRP), interleukin-6 (IL-6)), and a disturbed coagulation\/fibrinolysis profile (prothrombin fragment F1,2, D-dimer, plasminogen activity, antiplasmin activity). Increased RAS activity (renin), endothelial dysfunction (vWF), coagulation parameters (D-dimer, prothrombin fragment F1,2) and inflammation (CRP, IL-6) were significantly altered in COVID patients and followed similar trends from mild-COVID to ARDS-COVID. In CIRR patients, ACE activity was linked to IL-6 (\u03c1 = 0.26; p = 0.003), independently correlated with VWF antigen (aB: 0.10; p = 0.001), and was inversely associated with prothrombin fragment F1,2 (aB: \u22120.03; p = 0.023) and antiplasmin activity (aB: \u22120.58; p = 0.006), after adjusting for liver disease severity. (4) Conclusions: The considerable upregulation of the RAS in Child\u2212Pugh B\/C cirrhosis is linked to systemic inflammation, endothelial dysfunction, and abnormal coagulation profile. The cirrhosis-associated abnormalities of ACE, IL-6, VWF antigen, and antiplasmin parallel those observed in severe COVID-19.<\/jats:p>","DOI":"10.3390\/jpm11121264","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T01:43:22Z","timestamp":1638323002000},"page":"1264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cirrhosis-Associated RAS-Inflammation-Coagulation Axis Anomalies: Parallels to Severe COVID-19"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3398-6120","authenticated-orcid":false,"given":"Lukas","family":"Hartl","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Jachs","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedikt","family":"Simbrunner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-8518","authenticated-orcid":false,"given":"David J. M.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0411-166X","authenticated-orcid":false,"given":"Georg","family":"Semmler","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Gompelmann","sequence":"additional","affiliation":[{"name":"Division of Pulmonology, Department of Medicine II, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Szekeres","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Quehenberger","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1275-6425","authenticated-orcid":false,"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4904-5133","authenticated-orcid":false,"given":"Bernhard","family":"Scheiner","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4590-3583","authenticated-orcid":false,"given":"Thomas","family":"Reiberger","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Christian Doppler Lab for Portal Hypertension and Liver Fibrosis, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1111\/febs.15375","article-title":"A Guide to COVID-19: A global pandemic caused by the novel coronavirus SARS-CoV-2","volume":"287","author":"Atzrodt","year":"2020","journal-title":"FEBS J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1001\/jama.2020.12839","article-title":"Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review","volume":"324","author":"Wiersinga","year":"2020","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/liv.14730","article-title":"Pathophysiological mechanisms of liver injury in COVID-19","volume":"41","author":"Nardo","year":"2021","journal-title":"Liver Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N. 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