{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:58:39Z","timestamp":1793336319480,"version":"4.5.0"},"reference-count":44,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","journal-of-hepatology.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Hepatology"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1016\/j.jhep.2025.09.016","type":"journal-article","created":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T02:39:18Z","timestamp":1758940758000},"page":"86-98","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"title":["Phase II INTEGRIS-PSC trial of bexotegrast, an \u03b1v\u03b26\/\u03b1v\u03b21 integrin inhibitor, in primary sclerosing cholangitis"],"prefix":"10.1016","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6736-2255","authenticated-orcid":false,"given":"Gideon M.","family":"Hirschfield","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8553-3652","authenticated-orcid":false,"given":"Kris V.","family":"Kowdley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palak J.","family":"Trivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertus","family":"Eksteen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal","family":"Hameed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9588-9364","authenticated-orcid":false,"given":"Aparna","family":"Goel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7754-7694","authenticated-orcid":false,"given":"K. Gautham","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8295-9076","authenticated-orcid":false,"given":"Eric","family":"Orman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9547-2809","authenticated-orcid":false,"given":"Deepak","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9ric A.","family":"Lefebvre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna R.","family":"Schaub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahru C.","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-4842","authenticated-orcid":false,"given":"Chris N.","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Pencek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Thorburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2511-7980","authenticated-orcid":false,"given":"Aldo J.","family":"Montano-Loza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4264-1928","authenticated-orcid":false,"given":"Christoph","family":"Schramm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Bowlus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1275-6425","authenticated-orcid":false,"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5498-6037","authenticated-orcid":false,"given":"Cynthia","family":"Levy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhep.2025.09.016_bib1","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1053\/j.gastro.2024.01.049","article-title":"Immunopathogenesis of primary biliary cholangitis, primary sclerosing cholangitis and autoimmune hepatitis: themes and concepts","volume":"166","author":"Trivedi","year":"2024","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhep.2025.09.016_bib2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/1471-230X-11-83","article-title":"The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population","volume":"11","author":"Toy","year":"2011","journal-title":"BMC Gastroenterol"},{"key":"10.1016\/j.jhep.2025.09.016_bib3","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/S0140-6736(13)60096-3","article-title":"Primary sclerosing cholangitis","volume":"382","author":"Hirschfield","year":"2013","journal-title":"Lancet"},{"key":"10.1016\/j.jhep.2025.09.016_bib4","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/MOG.0000000000000333","article-title":"The evolution of natural history of primary sclerosing cholangitis","volume":"33","author":"Takakura","year":"2017","journal-title":"Curr Opin Gastroenterol"},{"key":"10.1016\/j.jhep.2025.09.016_bib5","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1136\/gutjnl-2018-317993","article-title":"British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis","volume":"68","author":"Chapman","year":"2019","journal-title":"Gut"},{"key":"10.1016\/j.jhep.2025.09.016_bib6","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1177\/2040622315605821","article-title":"A review of the medical treatment of primary sclerosing cholangitis in the 21st century","volume":"7","author":"Goode","year":"2016","journal-title":"Ther Adv Chronic Dis"},{"key":"10.1016\/j.jhep.2025.09.016_bib7","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/apt.15148","article-title":"Systematic review with meta-analysis: risk factors for recurrent primary sclerosing cholangitis after liver transplantation","volume":"49","author":"Steenstraten","year":"2019","journal-title":"Aliment Pharmacol Ther"},{"key":"10.1016\/j.jhep.2025.09.016_bib8","doi-asserted-by":"crossref","first-page":"3405","DOI":"10.3390\/jcm12103405","article-title":"Transplantation for primary sclerosing cholangitis: outcomes and recurrence","volume":"12","author":"Saner","year":"2023","journal-title":"J Clin Med"},{"key":"10.1016\/j.jhep.2025.09.016_bib9","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1016\/j.cgh.2021.08.039","article-title":"Epidemiology, natural history, and outcomes of primary sclerosing cholangitis: a systematic review of population-based studies","volume":"20","author":"Trivedi","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1016\/j.jhep.2025.09.016_bib10","article-title":"Recurrence of autoimmune liver diseases after liver transplantation: review and expert opinion statement","author":"Montano-Loza","year":"2024","journal-title":"Liver Transpl"},{"issue":"1","key":"10.1016\/j.jhep.2025.09.016_bib11","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jhep.2023.09.031","article-title":"Inflammatory bowel disease and primary sclerosing cholangitis: one disease or two?","volume":"80","author":"van Munster","year":"2024","journal-title":"J Hepatol"},{"key":"10.1016\/j.jhep.2025.09.016_bib12","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1016\/j.cell.2023.07.036","article-title":"TGF-\u03b2 signaling in health and disease","volume":"186","author":"Massagu\u00e9","year":"2023","journal-title":"Cell"},{"key":"10.1016\/j.jhep.2025.09.016_bib13","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1053\/j.gastro.2021.04.064","article-title":"TGF-\u03b2 signaling in liver, pancreas, and gastrointestinal diseases and cancer","volume":"161","author":"Gough","year":"2021","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhep.2025.09.016_bib14","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1111\/febs.13665","article-title":"TGF-\u03b2 signalling and liver disease","volume":"283","author":"Fabregat","year":"2016","journal-title":"FEBS J"},{"key":"10.1016\/j.jhep.2025.09.016_bib15","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.bbadis.2012.10.005","article-title":"Integrin-mediated regulation of TGF\u03b2 in fibrosis","volume":"1832","author":"Henderson","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.jhep.2025.09.016_bib16","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/hep.28274","article-title":"Integrin \u03b1v\u03b26 critically regulates hepatic progenitor cell function and promotes ductular reaction, fibrosis, and tumorigenesis","volume":"63","author":"Peng","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2025.09.016_bib17","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaa5094","article-title":"The \u03b1v\u03b21 integrin plays a critical in vivo role in tissue fibrosis","volume":"7","author":"Reed","year":"2015","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.jhep.2025.09.016_bib18","article-title":"Multimodal imaging demonstrates antifibrotic effects of targeting \u03b1v\u03b26\/\u03b1v\u03b21 integrins in biliary fibrosis","author":"Ning","year":"2025","journal-title":"Invest Radiol"},{"key":"10.1016\/j.jhep.2025.09.016_bib19","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s12026-022-09267-y","article-title":"Research progress on drugs targeting the TGF-\u03b2 signaling pathway in fibrotic diseases","volume":"70","author":"Shi","year":"2022","journal-title":"Immunol Res"},{"key":"10.1016\/j.jhep.2025.09.016_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2022.115905","article-title":"Lung-restricted ALK5 inhibition avoids systemic toxicities associated with TGF\u03b2 pathway inhibition","volume":"438","author":"Maher","year":"2022","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1016\/j.jhep.2025.09.016_bib21","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.jhep.2007.11.021","article-title":"Integrin alphavbeta6 is a marker of the progression of biliary and portal liver fibrosis and a novel target for antifibrotic therapies","volume":"48","author":"Popov","year":"2008","journal-title":"J Hepatol"},{"key":"10.1016\/j.jhep.2025.09.016_bib22","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1053\/j.gastro.2008.04.009","article-title":"Inhibition of integrin alphavbeta6 on cholangiocytes blocks transforming growth factor-beta activation and retards biliary fibrosis progression","volume":"135","author":"Patsenker","year":"2008","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhep.2025.09.016_bib23","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s12931-021-01863-0","article-title":"Dual inhibition of \u03b1v\u03b26 and \u03b1v\u03b21 reduces fibrogenesis in lung tissue explants from patients with IPF","volume":"22","author":"Decaris","year":"2021","journal-title":"Respir Res"},{"key":"10.1016\/j.jhep.2025.09.016_bib24","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1164\/rccm.202403-0636OC","article-title":"Bexotegrast in patients with idiopathic pulmonary fibrosis: the INTEGRIS-IPF study","volume":"210","author":"Lancaster","year":"2024","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jhep.2025.09.016_bib25","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1164\/rccm.202410-1934OC","article-title":"Dual \u03b1v\u03b26 and \u03b1v\u03b21 inhibition over 12 weeks reduces active type 1 collagen deposition in individuals with idiopathic pulmonary fibrosis: a phase 2, double-blind, placebo-controlled clinical trial","volume":"211","author":"Montesi","year":"2025","journal-title":"Am J Respir Crit Care Med"},{"key":"10.1016\/j.jhep.2025.09.016_bib26","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/ijd.12645","article-title":"The Worst Itch Numeric Rating Scale for patients with moderate to severe plaque psoriasis or psoriatic arthritis","volume":"54","author":"Naegeli","year":"2015","journal-title":"Int J Dermatol"},{"key":"10.1016\/j.jhep.2025.09.016_bib27","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s00261-020-02731-z","article-title":"Gadoxetic acid-enhanced MRI in primary sclerosing cholangitis: added value in assessing liver function and monitoring disease progression","volume":"46","author":"Elkilany","year":"2021","journal-title":"Abdom Radiol (Ny)"},{"key":"10.1016\/j.jhep.2025.09.016_bib28","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.cgh.2018.05.011","article-title":"An imaging biomarker for assessing hepatic function in patients with primary sclerosing cholangitis","volume":"17","author":"Schulze","year":"2019","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"3","key":"10.1016\/j.jhep.2025.09.016_bib29","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jhep.2018.10.035","article-title":"Effect of NGM282, an FGF19 analogue, in primary sclerosing cholangitis: a multicenter, randomized, double-blind, placebo-controlled phase II trial","volume":"70","author":"Hirschfield","year":"2019","journal-title":"J Hepatol"},{"issue":"3","key":"10.1016\/j.jhep.2025.09.016_bib30","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1002\/hep.30509","article-title":"The nonsteroidal farnesoid X receptor agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with primary sclerosing cholangitis","volume":"70","author":"Trauner","year":"2019","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2025.09.016_bib31","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1038\/ajg.2011.156","article-title":"High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis","volume":"106","author":"Eaton","year":"2011","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.jhep.2025.09.016_bib32","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/hep.23294","article-title":"Diagnosis and management of primary sclerosing cholangitis","volume":"51","author":"Chapman","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2025.09.016_bib33","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1002\/hep.23082","article-title":"High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis","volume":"50","author":"Lindor","year":"2009","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2025.09.016_bib34","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12876-023-02653-2","article-title":"PRIMIS: design of a pivotal, randomized, phase 3 study evaluating the safety and efficacy of the nonsteroidal farnesoid X receptor agonist cilofexor in noncirrhotic patients with primary sclerosing cholangitis","volume":"23","author":"Trauner","year":"2023","journal-title":"BMC Gastroenterol"},{"key":"10.1016\/j.jhep.2025.09.016_bib35","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1136\/jcp.48.10.933","article-title":"Sampling variability of percutaneous liver biopsy in primary sclerosing cholangitis","volume":"48","author":"Olsson","year":"1995","journal-title":"J Clin Pathol"},{"key":"10.1016\/j.jhep.2025.09.016_bib36","article-title":"Fluctuating biomarkers in primary sclerosing cholangitis: a longitudinal comparison of alkaline phosphatase, liver stiffness, and ELF","volume":"3","author":"Fossdal","year":"2021","journal-title":"JHEP Rep"},{"key":"10.1016\/j.jhep.2025.09.016_bib37","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/hep.27825","article-title":"Enhanced liver fibrosis score predicts transplant-free survival in primary sclerosing cholangitis","volume":"62","author":"Vesterhus","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2025.09.016_bib38","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1111\/liv.13402","article-title":"Enhanced liver fibrosis test predicts transplant-free survival in primary sclerosing cholangitis, a multi-centre study","volume":"37","author":"de Vries","year":"2017","journal-title":"Liver Int"},{"key":"10.1016\/j.jhep.2025.09.016_bib39","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jhep.2013.03.016","article-title":"The Enhanced Liver Fibrosis (ELF) score: normal values, influence factors and proposed cut-off values","volume":"59","author":"Lichtinghagen","year":"2013","journal-title":"J Hepatol"},{"key":"10.1016\/j.jhep.2025.09.016_bib40","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cgh.2020.07.032","article-title":"Inter- and intra-individual variation, and limited prognostic utility, of serum alkaline phosphatase in a trial of patients with primary sclerosing cholangitis","volume":"19","author":"Trivedi","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1016\/j.jhep.2025.09.016_bib41","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3389\/fonc.2018.00357","article-title":"Transforming growth factor-\u03b2-induced cell plasticity in liver fibrosis and hepatocarcinogenesis","volume":"8","author":"Fabregat","year":"2018","journal-title":"Front Oncol"},{"key":"10.1016\/j.jhep.2025.09.016_bib42","first-page":"303","article-title":"The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters","volume":"5","author":"Nielsen","year":"2013","journal-title":"Am J Transl Res"},{"key":"10.1016\/j.jhep.2025.09.016_bib43","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/apt.14806","article-title":"Serological markers of extracellular matrix remodeling predict transplant-free survival in primary sclerosing cholangitis","volume":"48","author":"Nielsen","year":"2018","journal-title":"Aliment Pharmacol Ther"},{"key":"10.1016\/j.jhep.2025.09.016_bib44","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1053\/j.gastro.2013.12.030","article-title":"Baseline values and changes in liver stiffness measured by transient elastography are associated with severity of fibrosis and outcomes of patients with primary sclerosing cholangitis","volume":"146","author":"Corpechot","year":"2014","journal-title":"Gastroenterology"}],"container-title":["Journal of Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827825024985?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827825024985?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:29:43Z","timestamp":1773887383000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168827825024985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["S0168827825024985"],"URL":"https:\/\/doi.org\/10.1016\/j.jhep.2025.09.016","relation":{},"ISSN":["0168-8278"],"issn-type":[{"value":"0168-8278","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Phase II INTEGRIS-PSC trial of bexotegrast, an \u03b1v\u03b26\/\u03b1v\u03b21 integrin inhibitor, in primary sclerosing cholangitis","name":"articletitle","label":"Article Title"},{"value":"Journal of Hepatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhep.2025.09.016","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.","name":"copyright","label":"Copyright"}]}}