{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:20:10Z","timestamp":1791822010747,"version":"4.3.4"},"reference-count":46,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009068","name":"University of Bern","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009068","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jhep-reports.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JHEP Reports"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.jhepr.2025.101681","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T03:05:23Z","timestamp":1763694323000},"page":"101681","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["Carvedilol decreases hepatic vascular resistance by reducing fibrogenesis and reversing endothelial dysfunction in cirrhotic rats"],"prefix":"10.1016","volume":"8","author":[{"given":"Yeldos","family":"Nulan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-6746","authenticated-orcid":false,"given":"Eric","family":"Felli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8112-7366","authenticated-orcid":false,"given":"Sonia-Emilia","family":"Selicean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Prampolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4562-9016","authenticated-orcid":false,"given":"Annalisa","family":"Berzigotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-4089","authenticated-orcid":false,"given":"Jordi","family":"Gracia-Sancho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3414-0055","authenticated-orcid":false,"given":"Jaume","family":"Bosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"9930","key":"10.1016\/j.jhepr.2025.101681_bib1","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1016\/S0140-6736(14)60121-5","article-title":"Liver cirrhosis","volume":"383","author":"Tsochatzis","year":"2014","journal-title":"Lancet"},{"issue":"5","key":"10.1016\/j.jhepr.2025.101681_bib2","doi-asserted-by":"crossref","first-page":"906","DOI":"10.2105\/AJPH.2015.303033","article-title":"Causes and disparities in death rates among Urban American Indian and Alaska Native Populations, 1999-2009","volume":"106","author":"Jacobs-Wingo","year":"2016","journal-title":"Am J Public Health"},{"issue":"Suppl 1","key":"10.1016\/j.jhepr.2025.101681_bib3","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/j.jhep.2021.01.002","article-title":"Pathophysiology of decompensated cirrhosis: portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction","volume":"75","author":"Engelmann","year":"2021","journal-title":"J Hepatol"},{"issue":"11","key":"10.1016\/j.jhepr.2025.101681_bib4","article-title":"Mechanobiology of portal hypertension","volume":"5","author":"Felli","year":"2023","journal-title":"JHEP Rep"},{"issue":"7","key":"10.1016\/j.jhepr.2025.101681_bib5","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/S2468-1253(23)00438-7","article-title":"Pathophysiology and therapeutic options for cirrhotic portal hypertension","volume":"9","author":"Guixe-Muntet","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"4","key":"10.1016\/j.jhepr.2025.101681_bib6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41575-018-0097-3","article-title":"Hepatic microcirculation and mechanisms of portal hypertension","volume":"16","author":"Gracia-Sancho","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"2","key":"10.1016\/j.jhepr.2025.101681_bib7","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1478-3231.2011.02579.x","article-title":"Endothelial dysfunction in the regulation of cirrhosis and portal hypertension","volume":"32","author":"Iwakiri","year":"2012","journal-title":"Liver Int"},{"issue":"4","key":"10.1016\/j.jhepr.2025.101681_bib8","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.dld.2022.12.014","article-title":"The Baveno VII concept of cirrhosis recompensation","volume":"55","author":"Reiberger","year":"2023","journal-title":"Dig Liver Dis"},{"key":"10.1016\/j.jhepr.2025.101681_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107245","article-title":"The current landscape of antifibrotic therapy across different organs: a systematic approach","volume":"205","author":"Fuster-Martinez","year":"2024","journal-title":"Pharmacol Res"},{"issue":"9361","key":"10.1016\/j.jhepr.2025.101681_bib10","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/S0140-6736(03)12778-X","article-title":"Prevention of variceal rebleeding","volume":"361","author":"Bosch","year":"2003","journal-title":"Lancet"},{"issue":"10181","key":"10.1016\/j.jhepr.2025.101681_bib11","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1016\/S0140-6736(18)31875-0","article-title":"Beta blockers to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension (PREDESCI): a randomised, double-blind, placebo-controlled, multicentre trial","volume":"393","author":"Villanueva","year":"2019","journal-title":"Lancet"},{"issue":"6","key":"10.1016\/j.jhepr.2025.101681_bib12","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1002\/hep.23689","article-title":"Carvedilol for portal hypertension in patients with cirrhosis","volume":"51","author":"Bosch","year":"2010","journal-title":"Hepatology"},{"issue":"4","key":"10.1016\/j.jhepr.2025.101681_bib13","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1097\/HJH.0b013e3280127948","article-title":"Antioxidant activity of carvedilol in cardiovascular disease","volume":"25","author":"Dandona","year":"2007","journal-title":"J Hypertens"},{"issue":"3","key":"10.1016\/j.jhepr.2025.101681_bib14","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1136\/gut.2003.026658","article-title":"Hepatic fibrogenesis requires sympathetic neurotransmitters","volume":"53","author":"Oben","year":"2004","journal-title":"Gut"},{"issue":"2","key":"10.1016\/j.jhepr.2025.101681_bib15","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/jcmm.13988","article-title":"4 in 1: antibody-free protocol for isolating the main hepatic cells from healthy and cirrhotic single rat livers","volume":"23","author":"Fernandez-Iglesias","year":"2019","journal-title":"J Cell Mol Med"},{"issue":"1","key":"10.1016\/j.jhepr.2025.101681_bib16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/hep.28264","article-title":"Development of hyperdynamic circulation and response to beta-blockers in compensated cirrhosis with portal hypertension","volume":"63","author":"Villanueva","year":"2016","journal-title":"Hepatology"},{"issue":"11","key":"10.1016\/j.jhepr.2025.101681_bib17","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.5858\/2000-124-1599-ROHC","article-title":"Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis","volume":"124","author":"Wanless","year":"2000","journal-title":"Arch Pathol Lab Med"},{"issue":"3","key":"10.1016\/j.jhepr.2025.101681_bib18","doi-asserted-by":"crossref","DOI":"10.3390\/cancers15030583","article-title":"The beta-blocker carvedilol prevents benzo(a)pyrene-induced lung toxicity, inflammation and carcinogenesis","volume":"15","author":"Shahid","year":"2023","journal-title":"Cancers (Basel)"},{"issue":"2","key":"10.1016\/j.jhepr.2025.101681_bib19","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jjcc.2019.07.011","article-title":"Effects of carvedilol vs bisoprolol on inflammation and oxidative stress in patients with chronic heart failure","volume":"75","author":"Toyoda","year":"2020","journal-title":"J Cardiol"},{"key":"10.1016\/j.jhepr.2025.101681_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2022.109119","article-title":"Carvedilol attenuates brain damage in mice with hepatic encephalopathy","volume":"111","author":"Amirshahrokhi","year":"2022","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"10.1016\/j.jhepr.2025.101681_bib21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s11901-023-00598-4","article-title":"Emerging therapeutic targets for portal hypertension","volume":"22","author":"Felli","year":"2023","journal-title":"Curr Hepatol Rep"},{"issue":"11","key":"10.1016\/j.jhepr.2025.101681_bib22","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1136\/gutjnl-2012-304182","article-title":"Carvedilol: the beta-blocker of choice for portal hypertension?","volume":"62","author":"Bosch","year":"2013","journal-title":"Gut"},{"issue":"6","key":"10.1016\/j.jhepr.2025.101681_bib23","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/apt.12634","article-title":"Systematic review with meta-analysis: the haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis","volume":"39","author":"Sinagra","year":"2014","journal-title":"Aliment Pharmacol Ther"},{"issue":"4","key":"10.1016\/j.jhepr.2025.101681_bib24","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.jhep.2022.12.005","article-title":"Beta-blockers in the era of precision medicine in patients with cirrhosis","volume":"78","author":"Albillos","year":"2023","journal-title":"J Hepatol"},{"issue":"4","key":"10.1016\/j.jhepr.2025.101681_bib25","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1016\/j.jhep.2022.05.021","article-title":"Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis","volume":"77","author":"Villanueva","year":"2022","journal-title":"J Hepatol"},{"issue":"5","key":"10.1016\/j.jhepr.2025.101681_bib26","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s13318-016-0391-9","article-title":"Antifibrotic effects of carvedilol and impact of liver fibrosis on carvedilol pharmacokinetics in a rat model","volume":"42","author":"El-Demerdash","year":"2017","journal-title":"Eur J Drug Metab Pharmacokinet"},{"issue":"6","key":"10.1016\/j.jhepr.2025.101681_bib27","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1002\/hep.1840360612","article-title":"Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis","volume":"36","author":"Banares","year":"2002","journal-title":"Hepatology"},{"issue":"4","key":"10.1016\/j.jhepr.2025.101681_bib28","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1002\/hep.22166","article-title":"Increased oxidative stress in cirrhotic rat livers: a potential mechanism contributing to reduced nitric oxide bioavailability","volume":"47","author":"Gracia-Sancho","year":"2008","journal-title":"Hepatology"},{"issue":"2","key":"10.1016\/j.jhepr.2025.101681_bib29","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1527-3466.2001.tb00061.x","article-title":"Carvedilol: molecular and cellular basis for its multifaceted therapeutic potential","volume":"19","author":"Cheng","year":"2001","journal-title":"Cardiovasc Drug Rev"},{"issue":"17","key":"10.1016\/j.jhepr.2025.101681_bib30","doi-asserted-by":"crossref","first-page":"8969","DOI":"10.1074\/jbc.R115.713313","article-title":"The beta-arrestins: multifunctional regulators of G protein-coupled receptors","volume":"291","author":"Smith","year":"2016","journal-title":"J Biol Chem"},{"issue":"42","key":"10.1016\/j.jhepr.2025.101681_bib31","doi-asserted-by":"crossref","first-page":"16657","DOI":"10.1073\/pnas.0707936104","article-title":"A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling","volume":"104","author":"Wisler","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"10.1016\/j.jhepr.2025.101681_bib32","doi-asserted-by":"crossref","first-page":"7109","DOI":"10.1038\/s41467-022-34765-w","article-title":"How Carvedilol activates beta(2)-adrenoceptors","volume":"13","author":"Benkel","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"10.1016\/j.jhepr.2025.101681_bib33","doi-asserted-by":"crossref","first-page":"7866","DOI":"10.1038\/s41467-023-42848-5","article-title":"How carvedilol does not activate beta(2)-adrenoceptors","volume":"14","author":"Lefkowitz","year":"2023","journal-title":"Nat Commun"},{"issue":"1","key":"10.1016\/j.jhepr.2025.101681_bib34","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s12072-021-10135-4","article-title":"Regression of portal hypertension: underlying mechanisms and therapeutic strategies","volume":"15","author":"Selicean","year":"2021","journal-title":"Hepatol Int"},{"issue":"9","key":"10.1016\/j.jhepr.2025.101681_bib35","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1136\/gutjnl-2014-308338","article-title":"KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins","volume":"64","author":"Marrone","year":"2015","journal-title":"Gut"},{"issue":"2","key":"10.1016\/j.jhepr.2025.101681_bib36","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.jhep.2012.09.010","article-title":"Recombinant human manganese superoxide dismutase reduces liver fibrosis and portal pressure in CCl4-cirrhotic rats","volume":"58","author":"Guillaume","year":"2013","journal-title":"J Hepatol"},{"issue":"3","key":"10.1016\/j.jhepr.2025.101681_bib37","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.jhep.2016.04.018","article-title":"Sinusoidal communication in liver fibrosis and regeneration","volume":"65","author":"Marrone","year":"2016","journal-title":"J Hepatol"},{"issue":"3","key":"10.1016\/j.jhepr.2025.101681_bib38","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/j.1527-5299.2002.00718.x","article-title":"Carvedilol: a nonselective beta blocking agent with antioxidant properties","volume":"8","author":"Book","year":"2002","journal-title":"Congest Heart Fail"},{"issue":"1","key":"10.1016\/j.jhepr.2025.101681_bib39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1172\/JCI88881","article-title":"Liver inflammation and fibrosis","volume":"127","author":"Koyama","year":"2017","journal-title":"J Clin Invest"},{"issue":"1","key":"10.1016\/j.jhepr.2025.101681_bib40","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/HEP.0000000000001148","article-title":"Hemodynamic effects of carvedilol plus simvastatin in cirrhosis with severe portal hypertension and suboptimal response to beta-blockers: a double-blind, placebo-controlled, randomized-trial","volume":"82","author":"Alvarado-Tapias","year":"2025","journal-title":"Hepatology"},{"issue":"4","key":"10.1016\/j.jhepr.2025.101681_bib41","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00281-022-00910-2","article-title":"TNF in the liver: targeting a central player in inflammation","volume":"44","author":"Tiegs","year":"2022","journal-title":"Semin Immunopathol"},{"issue":"5","key":"10.1016\/j.jhepr.2025.101681_bib42","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1002\/hep.510230538","article-title":"Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis","volume":"23","author":"Baroni","year":"1996","journal-title":"Hepatology"},{"issue":"2","key":"10.1016\/j.jhepr.2025.101681_bib43","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jhep.2006.09.014","article-title":"IFN-gamma abrogates profibrogenic TGF-beta signaling in liver by targeting expression of inhibitory and receptor Smads","volume":"46","author":"Weng","year":"2007","journal-title":"J Hepatol"},{"issue":"5","key":"10.1016\/j.jhepr.2025.101681_bib44","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.jhep.2024.10.028","article-title":"Blood markers for type-1,-2, and -3 inflammation are associated with severity of acutely decompensated cirrhosis","volume":"82","author":"Cao","year":"2025","journal-title":"J Hepatol"},{"issue":"6","key":"10.1016\/j.jhepr.2025.101681_bib45","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.jhep.2014.07.006","article-title":"CXCL10 plays a key role as an inflammatory mediator and a non-invasive biomarker of non-alcoholic steatohepatitis","volume":"61","author":"Zhang","year":"2014","journal-title":"J Hepatol"},{"issue":"11","key":"10.1016\/j.jhepr.2025.101681_bib46","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.1172\/JCI41732","article-title":"Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice","volume":"120","author":"Berres","year":"2010","journal-title":"J Clin Invest"}],"container-title":["JHEP Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555925003647?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555925003647?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T19:42:44Z","timestamp":1778096564000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589555925003647"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":46,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["S2589555925003647"],"URL":"https:\/\/doi.org\/10.1016\/j.jhepr.2025.101681","relation":{},"ISSN":["2589-5559"],"issn-type":[{"value":"2589-5559","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Carvedilol decreases hepatic vascular resistance by reducing fibrogenesis and reversing endothelial dysfunction in cirrhotic rats","name":"articletitle","label":"Article Title"},{"value":"JHEP Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhepr.2025.101681","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).","name":"copyright","label":"Copyright"}],"article-number":"101681"}}