{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T05:19:16Z","timestamp":1793855956317,"version":"4.6.1"},"reference-count":36,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:00:00Z","timestamp":1657843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015311","name":"Novartis Institutes for BioMedical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015311","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018262","name":"Intercept Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018262","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020406","name":"Dr. Falk Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jhep-reports.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JHEP Reports"],"published-print":{"date-parts":[[2022,11]]},"DOI":"10.1016\/j.jhepr.2022.100544","type":"journal-article","created":{"date-parts":[[2022,7,20]],"date-time":"2022-07-20T23:26:20Z","timestamp":1658359580000},"page":"100544","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":46,"title":["Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis"],"prefix":"10.1016","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4264-1928","authenticated-orcid":false,"given":"Christoph","family":"Schramm","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0470-9522","authenticated-orcid":false,"given":"Andrew","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon M.","family":"Hirschfield","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"}]},{"given":"Kris V.","family":"Kowdley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Milkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5406-4603","authenticated-orcid":false,"given":"Ewa","family":"Janczewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Sergeevna","family":"Malova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne","family":"Sanni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Koo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhajit","family":"Choudhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd B.","family":"Klickstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Badman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhepr.2022.100544_bib1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jhep.2017.03.022","article-title":"EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis","volume":"67","year":"2017","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhepr.2022.100544_bib2","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.jhep.2011.10.025","article-title":"Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review","volume":"56","author":"Boonstra","year":"2012","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhepr.2022.100544_bib3","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1136\/gutjnl-2017-315259","article-title":"The British Society of Gastroenterology\/UK-PBC primary biliary cholangitis treatment and management guidelines","volume":"67","author":"Hirschfield","year":"2018","journal-title":"Gut"},{"key":"10.1016\/j.jhepr.2022.100544_bib4","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/hep.30145","article-title":"Primary biliary cholangitis: 2018 Practice guidance from the American Association for the Study of Liver Diseases","volume":"69","author":"Lindor","year":"2019","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100544_bib5","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/S0140-6736(15)00154-3","article-title":"Primary biliary cirrhosis","volume":"386","author":"Carey","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.jhepr.2022.100544_bib6","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1056\/NEJM199405123301903","article-title":"Ursodiol for the long-term treatment of primary biliary cirrhosis","volume":"330","author":"Poupon","year":"1994","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jhepr.2022.100544_bib7","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1056\/NEJM199105303242204","article-title":"A\u00a0multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis","volume":"324","author":"Poupon","year":"1991","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jhepr.2022.100544_bib8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.jhep.2019.04.001","article-title":"Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis","volume":"71","author":"Harms","year":"2019","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhepr.2022.100544_bib9","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/hep.22428","article-title":"Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis","volume":"48","author":"Corpechot","year":"2008","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100544_bib10","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1021\/jm025529g","article-title":"6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity","volume":"45","author":"Pellicciari","year":"2002","journal-title":"J\u00a0Med Chem"},{"key":"10.1016\/j.jhepr.2022.100544_bib11","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1172\/JCI18945","article-title":"Hepatoprotection by the farnesoid X receptor agonist GW4064 in rat models of intra- and extrahepatic cholestasis","volume":"112","author":"Liu","year":"2003","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jhepr.2022.100544_bib12","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1053\/j.gastro.2014.12.005","article-title":"Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid","volume":"148","author":"Hirschfield","year":"2015","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhepr.2022.100544_bib13","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A\u00a0placebo-controlled trial of obeticholic acid in primary biliary cholangitis","volume":"375","author":"Nevens","year":"2016","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jhepr.2022.100544_bib14","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S2468-1253(19)30094-9","article-title":"Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study","volume":"4","author":"Trauner","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"10.1016\/j.jhepr.2022.100544_bib15","first-page":"654","article-title":"Use of obeticholic acid in patients with primary biliary cholangitis","volume":"14","author":"Brown","year":"2018","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"10.1016\/j.jhepr.2022.100544_bib16","doi-asserted-by":"crossref","first-page":"9960","DOI":"10.1021\/acs.jmedchem.7b00907","article-title":"Discovery of tropifexor (LJN452), a highly potent non-bile acid FXR agonist for the treatment of cholestatic liver diseases and nonalcoholic steatohepatitis (NASH)","volume":"60","author":"Tully","year":"2017","journal-title":"J\u00a0Med Chem"},{"key":"10.1016\/j.jhepr.2022.100544_bib17","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1002\/hep4.1368","article-title":"Tropifexor-mediated abrogation of steatohepatitis and fibrosis is associated with the antioxidative gene expression profile in rodents","volume":"3","author":"Hernandez","year":"2019","journal-title":"Hepatol Commun"},{"key":"10.1016\/j.jhepr.2022.100544_bib18","first-page":"S97","article-title":"A\u00a0novel, highly potent, non-bile acid FXR agonist for the treatment of NASH and cholestasis","volume":"10","author":"Laffitte","year":"2016","journal-title":"Hepatol Int"},{"key":"10.1016\/j.jhepr.2022.100544_bib19","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/cpdd.762","article-title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel non-bile acid FXR agonist tropifexor (LJN452) in healthy volunteers","volume":"9","author":"Badman","year":"2020","journal-title":"Clin Pharmacol Drug Dev"},{"key":"10.1016\/j.jhepr.2022.100544_bib20","first-page":"1479A","article-title":"Tropifexor, a highly potent FXR agonist, produces robust and dose-dependent reductions in hepatic fat and serum alanine aminotransferase in patients with fibrotic NASH after 12 weeks of therapy: FLIGHT-FXR Part C interim results","volume":"70","author":"Lucas","year":"2019","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100544_bib21","first-page":"1460A","article-title":"Tropifexor (TXR), an FXR agonist for the treatment of NASH \u2013 interim results from first two parts of phase 2b study FLIGHT-FXR","volume":"68","author":"Sanyal","year":"2018","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100544_bib22","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1111\/apt.15967","article-title":"Randomised clinical trial: significant biochemical and colonic transit effects of the farnesoid X receptor agonist tropifexor in patients with primary bile acid diarrhoea","volume":"52","author":"Camilleri","year":"2020","journal-title":"Aliment Pharmacol Ther"},{"key":"10.1016\/j.jhepr.2022.100544_bib23","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1053\/j.gastro.2015.02.037","article-title":"Targeting the FXR nuclear receptor to treat liver disease","volume":"148","author":"Neuschwander-Tetri","year":"2015","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhepr.2022.100544_bib24","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.cgh.2020.08.006","article-title":"Measurement of gamma glutamyl transferase to determine risk of liver transplantation or death in patients with primary biliary cholangitis","volume":"19","author":"Gerussi","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1016\/j.jhepr.2022.100544_bib25","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1136\/gut.2005.065862","article-title":"Development, validation, and evaluation of the PBC-40, a disease specific health related quality of life measure for primary biliary cirrhosis","volume":"54","author":"Jacoby","year":"2005","journal-title":"Gut"},{"key":"10.1016\/j.jhepr.2022.100544_bib26","doi-asserted-by":"crossref","first-page":"497","DOI":"10.2340\/00015555-1265","article-title":"Visual analogue scale: evaluation of the instrument for the assessment of pruritus","volume":"92","author":"Reich","year":"2012","journal-title":"Acta Derm Venereol"},{"key":"10.1016\/j.jhepr.2022.100544_bib27","doi-asserted-by":"crossref","first-page":"e796","DOI":"10.1016\/S0618-8278(19)31587-7","article-title":"Tropifexor, a farnesoid X receptor agonist for the treatment of non-alcoholic steatohepatitis: interim results based on baseline body mass index from first two parts of Phase 2b study FLIGHT-FXR","volume":"70","author":"Sanyal","year":"2019","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhepr.2022.100544_bib28","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41395-018-0390-3","article-title":"Diagnosis and management of primary biliary cholangitis","volume":"114","author":"Younossi","year":"2019","journal-title":"Am J Gastroenterol"},{"key":"10.1016\/j.jhepr.2022.100544_bib29","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1053\/j.gastro.2014.08.029","article-title":"Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow-up study","volume":"147","author":"Lammers","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhepr.2022.100544_bib30","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1056\/NEJMoa1714519","article-title":"A\u00a0placebo-controlled trial of bezafibrate in primary biliary cholangitis","volume":"378","author":"Corpechot","year":"2018","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jhepr.2022.100544_bib31","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.jhepr.2022.100544_bib32","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1172\/JCI64551","article-title":"The TGR5 receptor mediates bile acid-induced itch and analgesia","volume":"123","author":"Alemi","year":"2013","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jhepr.2022.100544_bib33","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/hep.25748","article-title":"Serum autotaxin is increased in pruritus of cholestasis, but not of other origin, and responds to therapeutic interventions","volume":"56","author":"Kremer","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100544_bib34","doi-asserted-by":"crossref","first-page":"10525","DOI":"10.1073\/pnas.1903316116","article-title":"MRGPRX4 is a G protein-coupled receptor activated by bile acids that may contribute to cholestatic pruritus","volume":"116","author":"Meixiong","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jhepr.2022.100544_bib35","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.3389\/fphar.2018.01283","article-title":"Bile acids and their derivatives as potential modifiers of drug release and pharmacokinetic profiles","volume":"9","author":"Pavlovi\u0107","year":"2018","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.jhepr.2022.100544_bib36","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.aohep.2019.09.009","article-title":"Multiple therapeutic targets in rare cholestatic liver diseases: time to redefine treatment strategies","volume":"19","author":"Gerussi","year":"2020","journal-title":"Ann Hepatol"}],"container-title":["JHEP Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555922001161?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555922001161?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:29:10Z","timestamp":1762900150000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589555922001161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":36,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["S2589555922001161"],"URL":"https:\/\/doi.org\/10.1016\/j.jhepr.2022.100544","relation":{},"ISSN":["2589-5559"],"issn-type":[{"value":"2589-5559","type":"print"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis","name":"articletitle","label":"Article Title"},{"value":"JHEP Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhepr.2022.100544","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 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":"100544"}}