{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T22:52:23Z","timestamp":1757631143991,"version":"3.44.0"},"reference-count":189,"publisher":"Georg Thieme Verlag KG","issue":"03","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Liver Dis"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>Primary sclerosing cholangitis (PSC) is a rare, progressive cholestatic disease of unknown etiology and characterized by inflammation and stricturing of intrahepatic and\/or extrahepatic bile ducts. This process leads to bile duct scarring, progressive liver fibrosis, and end-stage liver disease. PSC is often associated with a specific form of inflammatory bowel disease and patients face a significant risk of developing cholangiocarcinoma and colorectal cancer. The clinical course of PSC can differ significantly between subtypes and affected individuals, representing a major obstacle to successful medical treatment trials. Numerous innovative therapeutic targets have been identified and, at least in part, explored, including nuclear and membrane receptors regulating bile acid metabolism and transport, modulation of gut microbiota, and signaling molecules involved in liver inflammation and fibrosis. Successful drug testing in preclinical PSC models as well as positive signals from some clinical studies justify hope. However, no medical treatment has so far been proven to improve transplant-free survival or overall survival in PSC patients. Disease-modifying drugs are urgently awaited. Despite ongoing efforts to improve study designs and implement treatment trials for novel drug targets, a central breakthrough has not yet been convincingly achieved. This situation might change in the near future. This article summarizes current research efforts aimed at developing medical treatments for PSC.<\/jats:p>","DOI":"10.1055\/a-2601-9426","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T19:30:41Z","timestamp":1748287841000},"page":"362-380","source":"Crossref","is-referenced-by-count":0,"title":["Emerging Targets for the Treatment of Primary Sclerosing Cholangitis"],"prefix":"10.1055","volume":"45","author":[{"given":"Elisabeth","family":"Tatscher","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samy","family":"Mady","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, 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Gacesa","year":"2022","journal-title":"Nature"},{"issue":"08","key":"ref12","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1053\/j.gastro.2017.02.038","article-title":"Patient age, sex, and inflammatory bowel disease phenotype associate with course of primary sclerosing cholangitis","volume":"152","author":"T J Weism\u00fcller","year":"2017","journal-title":"Gastroenterology"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.crohns.2011.07.015","article-title":"A unique clinical phenotype of primary sclerosing cholangitis associated with Crohn's disease","volume":"6","author":"J S Halliday","year":"2012","journal-title":"J Crohns Colitis"},{"issue":"05","key":"ref14","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1093\/ibd\/izx096","article-title":"Natural history of established and de novo inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis","volume":"24","author":"M A 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Gauss","year":"2013","journal-title":"World J Gastroenterol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s12016-014-8442-y","article-title":"Animal models in primary biliary cirrhosis and primary sclerosing cholangitis","volume":"48","author":"M J Pollheimer","year":"2015","journal-title":"Clin Rev Allergy Immunol"},{"issue":"02","key":"ref40","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng.3745","article-title":"Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease","volume":"49","author":"S G Ji","year":"2017","journal-title":"Nat Genet"},{"issue":"03","key":"ref41","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1053\/j.gastro.2009.11.046","article-title":"Genome-wide association analysis in primary sclerosing cholangitis","volume":"138","author":"T H Karlsen","year":"2010","journal-title":"Gastroenterology"},{"issue":"01","key":"ref42","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/ng.728","article-title":"Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci","volume":"43","author":"E Melum","year":"2011","journal-title":"Nat Genet"},{"issue":"03","key":"ref43","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1002\/hep.25977","article-title":"Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4","volume":"58","author":"D Ellinghaus","year":"2013","journal-title":"Hepatology"},{"issue":"07","key":"ref44","doi-asserted-by":"crossref","first-page":"820","DOI":"10.3109\/00365521.2012.682090","article-title":"Fine mapping and replication of genetic risk loci in primary sclerosing cholangitis","volume":"47","author":"B Srivastava","year":"2012","journal-title":"Scand J 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Dis"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/j.bbadis.2017.08.020","article-title":"Cholangiocytes in the pathogenesis of primary sclerosing cholangitis and development of cholangiocarcinoma","volume":"1864","author":"B K Chung","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"113512","DOI":"10.1016\/j.biopha.2022.113512","article-title":"Aberrant peribiliary gland niche exacerbates fibrosis in primary sclerosing cholangitis and a potential therapeutic strategy","volume":"153","author":"S Wu","year":"2022","journal-title":"Biomed Pharmacother"},{"issue":"04","key":"ref51","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.ajpath.2022.12.008","article-title":"Kupffer cells contested as early drivers in the pathogenesis of primary sclerosing cholangitis","volume":"193","author":"K De Muynck","year":"2023","journal-title":"Am J Pathol"},{"issue":"01","key":"ref52","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":"Z W Peng","year":"2016","journal-title":"Hepatology"},{"issue":"12","key":"ref53","doi-asserted-by":"crossref","first-page":"e162270","DOI":"10.1172\/jci.insight.162270","article-title":"CCL24 regulates biliary inflammation and fibrosis in primary sclerosing cholangitis","volume":"8","author":"R Greenman","year":"2023","journal-title":"JCI Insight"},{"issue":"01","key":"ref54","doi-asserted-by":"crossref","first-page":"100064","DOI":"10.1016\/j.jhepr.2019.100064","article-title":"A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage","volume":"2","author":"M Segal-Salto","year":"2020","journal-title":"JHEP Rep Innov Hepatol"},{"issue":"05","key":"ref55","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nrgastro.2016.154","article-title":"Genetics of primary sclerosing cholangitis and pathophysiological implications","volume":"14","author":"X Jiang","year":"2017","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"01","key":"ref56","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1572-0241.2006.00872.x","article-title":"Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study","volume":"102","author":"J J Tischendorf","year":"2007","journal-title":"Am J Gastroenterol"},{"issue":"02","key":"ref57","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/lt.21313","article-title":"Clinically recurrent primary sclerosing cholangitis following liver transplantation: a time course","volume":"14","author":"J Campsen","year":"2008","journal-title":"Liver Transpl"},{"issue":"04","key":"ref58","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1002\/hep.510290427","article-title":"Recurrence of primary sclerosing cholangitis following liver transplantation","volume":"29","author":"I W Graziadei","year":"1999","journal-title":"Hepatology"},{"issue":"05","key":"ref59","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1002\/hep.510300501","article-title":"Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis","volume":"30","author":"I W Graziadei","year":"1999","journal-title":"Hepatology"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"100186","DOI":"10.1016\/j.liver.2023.100186","article-title":"Outcomes of patients with primary sclerosing cholangitis after liver transplantation in a predominantly living donor liver transplant center","volume":"12","author":"M Harputluoglu","year":"2023","journal-title":"J Liver 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Hepatol"},{"issue":"03","key":"ref64","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/hep.1840160315","article-title":"Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial","volume":"16","author":"U Beuers","year":"1992","journal-title":"Hepatology"},{"issue":"10","key":"ref65","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1056\/NEJM199703063361003","article-title":"Ursodiol for primary sclerosing cholangitis","volume":"336","author":"K D Lindor","year":"1997","journal-title":"N Engl J Med"},{"issue":"01","key":"ref66","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0168-8278(05)80467-2","article-title":"Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period","volume":"20","author":"A Stiehl","year":"1994","journal-title":"J Hepatol"},{"issue":"05","key":"ref67","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1053\/j.gastro.2005.08.017","article-title":"High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study","volume":"129","author":"R Olsson","year":"2005","journal-title":"Gastroenterology"},{"issue":"03","key":"ref68","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":"K D Lindor","year":"2009","journal-title":"Hepatology"},{"issue":"03","key":"ref69","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1002\/hep.27074","article-title":"Prospective evaluation of ursodeoxycholic acid withdrawal in patients with primary sclerosing 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cholangiocarcinoma","volume":"77","author":"C L Bowlus","year":"2023","journal-title":"Hepatology"},{"issue":"03","key":"ref73","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.jhep.2022.05.011","article-title":"EASL clinical practice guidelines on sclerosing cholangitis","volume":"77","author":"European Association for the Study of the Liver","year":"2022","journal-title":"J Hepatol"},{"issue":"01","key":"ref74","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1053\/j.gastro.2004.04.009","article-title":"Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice","volume":"127","author":"P Fickert","year":"2004","journal-title":"Gastroenterology"},{"issue":"04","key":"ref75","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1053\/gast.2002.35948","article-title":"Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles","volume":"123","author":"P Fickert","year":"2002","journal-title":"Gastroenterology"},{"issue":"01","key":"ref76","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13578-024-01195-8","article-title":"Therapeutic potential of berberine in attenuating cholestatic liver injury: insights from a PSC mouse model","volume":"14","author":"Y Wang","year":"2024","journal-title":"Cell Biosci"},{"issue":"03","key":"ref77","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41564-018-0333-1","article-title":"Gut pathobionts underlie intestinal barrier dysfunction and liver T helper 17 cell immune response in primary sclerosing cholangitis","volume":"4","author":"N Nakamoto","year":"2019","journal-title":"Nat Microbiol"},{"issue":"11","key":"ref78","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.14309\/ajg.0000000000001999","article-title":"Berberine ursodeoxycholate for the treatment of primary sclerosing cholangitis: the search for the elusive pharmacologic Holy Grail will need to continue","volume":"117","author":"E M Yoshida","year":"2022","journal-title":"Am J Gastroenterol"},{"issue":"11","key":"ref79","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.14309\/ajg.0000000000001956","article-title":"A randomized, dose-finding, proof-of-concept study of berberine ursodeoxycholate in patients with primary sclerosing cholangitis","volume":"117","author":"K V Kowdley","year":"2022","journal-title":"Am J Gastroenterol"},{"issue":"06","key":"ref80","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1002\/hep.20943","article-title":"Novel biotransformation and physiological properties of norursodeoxycholic acid in humans","volume":"42","author":"A F Hofmann","year":"2005","journal-title":"Hepatology"},{"issue":"02","key":"ref81","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1053\/j.gastro.2005.10.018","article-title":"24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice","volume":"130","author":"P Fickert","year":"2006","journal-title":"Gastroenterology"},{"issue":"06","key":"ref82","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1002\/hep.22891","article-title":"Side chain structure determines unique physiologic and therapeutic properties of norursodeoxycholic acid in Mdr2\u2212\/\u2212 mice","volume":"49","author":"E Halilbasic","year":"2009","journal-title":"Hepatology"},{"issue":"06","key":"ref83","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.jhep.2013.01.026","article-title":"Differential effects of norUDCA and UDCA in obstructive cholestasis in mice","volume":"58","author":"P Fickert","year":"2013","journal-title":"J Hepatol"},{"issue":"04","key":"ref84","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.jhep.2014.11.020","article-title":"24-nor-ursodeoxycholic acid ameliorates inflammatory response and liver fibrosis in a murine model of hepatic schistosomiasis","volume":"62","author":"M Sombetzki","year":"2015","journal-title":"J Hepatol"},{"issue":"01","key":"ref85","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jhep.2017.02.019","article-title":"NorUrsodeoxycholic acid ameliorates cholemic nephropathy in bile duct ligated mice","volume":"67","author":"E Krones","year":"2017","journal-title":"J Hepatol"},{"issue":"03","key":"ref86","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1159\/000371904","article-title":"Potential of nor-ursodeoxycholic acid in cholestatic and metabolic disorders","volume":"33","author":"M Trauner","year":"2015","journal-title":"Dig Dis"},{"issue":"03","key":"ref87","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.jhep.2017.05.009","article-title":"norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis","volume":"67","author":"P Fickert","year":"2017","journal-title":"J Hepatol"},{"issue":"04","key":"ref88","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1053\/j.gastro.2018.06.038","article-title":"An FXR agonist reduces bile acid synthesis independently of increases in FGF19 in healthy volunteers","volume":"155","author":"A Al-Khaifi","year":"2018","journal-title":"Gastroenterology"},{"issue":"10","key":"ref89","doi-asserted-by":"crossref","first-page":"G940","DOI":"10.1152\/ajpgi.00398.2012","article-title":"Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids","volume":"304","author":"J H Zhang","year":"2013","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"33453","DOI":"10.1038\/srep33453","article-title":"FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis","volume":"6","author":"L Verbeke","year":"2016","journal-title":"Sci Rep"},{"issue":"06","key":"ref91","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1002\/hep.26939","article-title":"Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats","volume":"59","author":"L Verbeke","year":"2014","journal-title":"Hepatology"},{"issue":"02","key":"ref92","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ajpath.2014.10.009","article-title":"The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats","volume":"185","author":"L Verbeke","year":"2015","journal-title":"Am J Pathol"},{"issue":"05","key":"ref93","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.jhep.2015.12.010","article-title":"Obeticholic acid reduces bacterial translocation and inhibits intestinal inflammation in cirrhotic rats","volume":"64","author":"M \u00dabeda","year":"2016","journal-title":"J Hepatol"},{"issue":"04","key":"ref94","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.jhep.2017.01.013","article-title":"Steroidal or non-steroidal FXR agonists - is that the question?","volume":"66","author":"L Verbeke","year":"2017","journal-title":"J Hepatol"},{"issue":"07","key":"ref95","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A placebo-controlled trial of obeticholic acid in primary biliary cholangitis","volume":"375","author":"F Nevens","year":"2016","journal-title":"N Engl J Med"},{"issue":"06","key":"ref97","first-page":"1254A","article-title":"The AESOP trial: a randomized, double-blind, placebo-controlled, phase 2 study of obeticholic acid in patients with primary sclerosing cholangitis","volume":"66","author":"K VBC Kowdley","year":"2017","journal-title":"Hepatology"},{"issue":"08","key":"ref98","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1002\/hep4.1720","article-title":"Impact of obeticholic acid exposure on decompensation and mortality in primary biliary cholangitis and cirrhosis","volume":"5","author":"B V John","year":"2021","journal-title":"Hepatol Commun"},{"issue":"05","key":"ref99","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1002\/hep.29726","article-title":"Evolving role of obeticholic acid in primary biliary cholangitis","volume":"67","author":"C Levy","year":"2018","journal-title":"Hepatology"},{"issue":"19","key":"ref100","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.2174\/1568026614666141112094430","article-title":"Knocking on FXR's door: the \u201chammerhead\u201d-structure series of FXR agonists - amphiphilic isoxazoles with potent in vitro and in vivo activities","volume":"14","author":"C Gege","year":"2014","journal-title":"Curr Top Med Chem"},{"issue":"11","key":"ref101","doi-asserted-by":"crossref","first-page":"100874","DOI":"10.1016\/j.jhepr.2023.100874","article-title":"Non-steroidal FXR agonist cilofexor improves cholestatic liver injury in the Mdr2\u2212\n               \n               \/\u2212\n                mouse model of sclerosing cholangitis","volume":"5","author":"C D Fuchs","year":"2023","journal-title":"JHEP Rep Innov Hepatol"},{"issue":"03","key":"ref102","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":"M Trauner","year":"2019","journal-title":"Hepatology"},{"issue":"01","key":"ref103","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":"M Trauner","year":"2023","journal-title":"BMC Gastroenterol"},{"issue":"02","key":"ref104","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/s41591-022-02200-8","article-title":"Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a\/b trial","volume":"29","author":"A J Sanyal","year":"2023","journal-title":"Nat Med"},{"issue":"11","key":"ref105","doi-asserted-by":"crossref","first-page":"100544","DOI":"10.1016\/j.jhepr.2022.100544","article-title":"Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis","volume":"4","author":"C Schramm","year":"2022","journal-title":"JHEP Rep Innov Hepatol"},{"issue":"12","key":"ref106","doi-asserted-by":"crossref","first-page":"13575","DOI":"10.18632\/oncotarget.6185","article-title":"FGF19 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3\u03b2\/\u03b2- catenin signaling cascade via FGFR4 activation","volume":"7","author":"H Zhao","year":"2016","journal-title":"Oncotarget"},{"issue":"14","key":"ref107","doi-asserted-by":"crossref","first-page":"18394","DOI":"10.18632\/oncotarget.7817","article-title":"Identification of FGF19 as a prognostic marker and potential driver gene of lung squamous cell carcinomas in Chinese smoking patients","volume":"7","author":"Q Tan","year":"2016","journal-title":"Oncotarget"},{"issue":"24","key":"ref108","doi-asserted-by":"crossref","first-page":"38592","DOI":"10.18632\/oncotarget.16951","article-title":"Multiplexed gene expression profiling identifies the FGFR4 pathway as a novel biomarker in intrahepatic cholangiocarcinoma","volume":"8","author":"C Yoo","year":"2017","journal-title":"Oncotarget"},{"issue":"32","key":"ref109","doi-asserted-by":"crossref","first-page":"52329","DOI":"10.18632\/oncotarget.10750","article-title":"Up-regulation of fibroblast growth factor 19 and its receptor associates with progression from fatty liver to hepatocellular carcinoma","volume":"7","author":"Y Li","year":"2016","journal-title":"Oncotarget"},{"issue":"39","key":"ref110","doi-asserted-by":"crossref","first-page":"25572","DOI":"10.18632\/oncotarget.25385","article-title":"Diminished gallbladder filling, increased fecal bile acids, and promotion of colon epithelial cell proliferation and neoplasia in fibroblast growth factor 15-deficient mice","volume":"9","author":"K Cheng","year":"2018","journal-title":"Oncotarget"},{"issue":"07","key":"ref111","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.ajpath.2021.04.014","article-title":"The role of fibroblast growth factor 19 in hepatocellular carcinoma","volume":"191","author":"Z Chen","year":"2021","journal-title":"Am J Pathol"},{"issue":"03","key":"ref112","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":"G M Hirschfield","year":"2019","journal-title":"J Hepatol"},{"issue":"08","key":"ref113","doi-asserted-by":"crossref","first-page":"2265","DOI":"10.1194\/jlr.M005546","article-title":"Retinoic acid represses CYP7A1 expression in human hepatocytes and HepG2 cells by FXR\/RXR-dependent and independent mechanisms","volume":"51","author":"S Y Cai","year":"2010","journal-title":"J Lipid Res"},{"issue":"01","key":"ref114","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1124\/jpet.113.209353","article-title":"All-trans-retinoic acid improves cholestasis in \u03b1-naphthylisothiocyanate-treated rats and Mdr2-\/- mice","volume":"349","author":"S Y Cai","year":"2014","journal-title":"J Pharmacol Exp Ther"},{"issue":"02","key":"ref115","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1097\/MCG.0000000000000591","article-title":"Combination therapy of all-trans retinoic acid with ursodeoxycholic acid in patients with primary sclerosing cholangitis: a human pilot study","volume":"51","author":"D N Assis","year":"2017","journal-title":"J Clin Gastroenterol"},{"issue":"05","key":"ref116","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1002\/hep.26018","article-title":"Anticholestatic effects of bezafibrate in patients with primary biliary cirrhosis treated with ursodeoxycholic acid","volume":"57","author":"A Honda","year":"2013","journal-title":"Hepatology"},{"issue":"23","key":"ref117","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1056\/NEJMoa1714519","article-title":"A placebo-controlled trial of bezafibrate in primary biliary cholangitis","volume":"378","author":"C Corpechot","year":"2018","journal-title":"N Engl J Med"},{"issue":"01","key":"ref118","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","author":"European Association for the Study of the Liver","year":"2017","journal-title":"J Hepatol"},{"issue":"09","key":"ref119","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa2306185","article-title":"Efficacy and safety of elafibranor in primary biliary cholangitis","volume":"390","author":"K V Kowdley","year":"2024","journal-title":"N Engl J Med"},{"issue":"10","key":"ref120","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/S2468-1253(17)30246-7","article-title":"Seladelpar (MBX-8025), a selective PPAR-\u03b4 agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double-blind, randomised, placebo-controlled, phase 2, proof-of-concept study","volume":"2","author":"D Jones","year":"2017","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"09","key":"ref121","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1056\/NEJMoa2312100","article-title":"A phase 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Gastroenterol Hepatol"},{"issue":"01","key":"ref128","first-page":"235","article-title":"Long term effect of simvastatin in primary sclerosing cholangitits: a placebo-controlled, double-blind, multicenter phase III study (Piscatin)","volume":"4","author":"A MH Bergquist","year":"2022","journal-title":"Br J Gastroenterol"},{"key":"ref129","doi-asserted-by":"crossref","first-page":"931","DOI":"10.3389\/fphar.2018.00931","article-title":"Ileal bile acid transporter inhibition for the treatment of chronic constipation, cholestatic pruritus, and NASH","volume":"9","author":"S Al-Dury","year":"2018","journal-title":"Front Pharmacol"},{"issue":"06","key":"ref130","doi-asserted-by":"crossref","first-page":"e0153","DOI":"10.1097\/HC9.0000000000000153","article-title":"Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: open-label pilot study","volume":"7","author":"C L Bowlus","year":"2023","journal-title":"Hepatol Commun"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1016\/S0140-6736(21)01256-3","article-title":"Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study","volume":"398","author":"E Gonzales","year":"2021","journal-title":"Lancet"},{"issue":"09","key":"ref132","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/S2468-1253(22)00093-0","article-title":"Odevixibat treatment in progressive familial intrahepatic cholestasis: a randomised, placebo-controlled, phase 3 trial","volume":"7","author":"R J Thompson","year":"2022","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"9301","key":"ref133","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/S0140-6736(02)07374-9","article-title":"Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease","volume":"359","author":"A J Grant","year":"2002","journal-title":"Lancet"},{"issue":"02","key":"ref134","doi-asserted-by":"crossref","first-page":"173","DOI":"10.7861\/clinmedicine.4-2-173","article-title":"Lymphocyte homing in the pathogenesis of extra-intestinal manifestations of inflammatory bowel disease","volume":"4","author":"B Eksteen","year":"2004","journal-title":"Clin Med (Lond)"},{"issue":"06","key":"ref135","first-page":"589","article-title":"An overview of recent treatment options for primary sclerosing cholangitis","volume":"36","author":"I Mousavere","year":"2023","journal-title":"Ann Gastroenterol"},{"issue":"06","key":"ref136","doi-asserted-by":"crossref","first-page":"e015081","DOI":"10.1136\/bmjopen-2016-015081","article-title":"Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): a single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol","volume":"7","author":"K Arndtz","year":"2017","journal-title":"BMJ Open"},{"issue":"06","key":"ref137","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1136\/gutjnl-2016-312354","article-title":"Vascular adhesion protein-1 is elevated in primary sclerosing cholangitis, is predictive of clinical outcome and facilitates recruitment of gut-tropic lymphocytes to liver in a substrate-dependent manner","volume":"67","author":"P J Trivedi","year":"2018","journal-title":"Gut"},{"issue":"02","key":"ref138","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1172\/JCI73722","article-title":"Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis","volume":"125","author":"C J Weston","year":"2015","journal-title":"J Clin Invest"},{"issue":"06","key":"ref139","doi-asserted-by":"crossref","first-page":"e0158156","DOI":"10.1371\/journal.pone.0158156","article-title":"Antifibrotic effects of the dual CCR2\/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosis","volume":"11","author":"E Lefebvre","year":"2016","journal-title":"PLoS One"},{"issue":"05","key":"ref140","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1002\/hep.28682","article-title":"Chemokine (C-C motif) receptor 2-positive monocytes aggravate the early phase of acetaminophen-induced acute liver injury","volume":"64","author":"J C Mossanen","year":"2016","journal-title":"Hepatology"},{"issue":"09","key":"ref141","doi-asserted-by":"crossref","first-page":"e0184694","DOI":"10.1371\/journal.pone.0184694","article-title":"Differential impact of the dual CCR2\/CCR5 inhibitor cenicriviroc on migration of monocyte and lymphocyte subsets in acute liver injury","volume":"12","author":"T Puengel","year":"2017","journal-title":"PLoS One"},{"issue":"04","key":"ref142","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1002\/hep.29544","article-title":"Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver 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Med"},{"issue":"05","key":"ref146","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1053\/jhep.2001.24231","article-title":"MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease)","volume":"33","author":"A J Grant","year":"2001","journal-title":"Hepatology"},{"issue":"09","key":"ref147","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1007\/s10620-013-2755-1","article-title":"Mucosal addressin cell adhesion molecule (MAdCAM-1) expression is upregulated in the cirrhotic liver and immunolocalises to the peribiliary plexus and lymphoid aggregates","volume":"58","author":"A Ala","year":"2013","journal-title":"Dig Dis Sci"},{"key":"ref148","doi-asserted-by":"crossref","first-page":"bcr2017220351","DOI":"10.1136\/bcr-2017-220351","article-title":"Vedolizumab: a novel medical intervention in the treatment of primary sclerosing cholangitis","volume":"2017","author":"D Westerveld","year":"2017","journal-title":"BMJ Case Rep"},{"issue":"12","key":"ref149","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1093\/ecco-jcc\/jjx090","article-title":"Successful treatment with vedolizumab in a patient with chronic refractory pouchitis and primary sclerosing cholangitis","volume":"11","author":"M Coletta","year":"2017","journal-title":"J Crohns Colitis"},{"issue":"06","key":"ref150","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/apt.14525","article-title":"Vedolizumab in patients with concurrent primary sclerosing cholangitis and inflammatory bowel disease does not improve liver biochemistry but is safe and effective for the bowel disease","volume":"47","author":"B Christensen","year":"2018","journal-title":"Aliment Pharmacol Ther"},{"issue":"07","key":"ref151","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/acn3.51574","article-title":"A double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis","volume":"9","author":"R J Fox","year":"2022","journal-title":"Ann Clin Transl Neurol"},{"issue":"08","key":"ref152","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.crohns.2012.09.016","article-title":"Efficacy, safety and tolerability of vidofludimus in patients with inflammatory bowel disease: the ENTRANCE study","volume":"7","author":"K R Herrlinger","year":"2013","journal-title":"J Crohns Colitis"},{"issue":"04","key":"ref153","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s40268-019-00286-z","article-title":"The selective oral immunomodulator vidofludimus in patients with active rheumatoid arthritis: safety results from the COMPONENT study","volume":"19","author":"A Muehler","year":"2019","journal-title":"Drugs R D"},{"issue":"07","key":"ref154","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1002\/hep4.1926","article-title":"A pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis","volume":"6","author":"E J Carey","year":"2022","journal-title":"Hepatol Commun"},{"issue":"06","key":"ref157","doi-asserted-by":"crossref","first-page":"e0454","DOI":"10.1097\/HC9.0000000000000454","article-title":"IL-17 signaling in primary sclerosing cholangitis patient-derived organoids","volume":"8","author":"A S Garcia Moreno","year":"2024","journal-title":"Hepatol Commun"},{"volume-title":"IL-17 signaling in primary sclerosing cholangitis patient-derived organoids","year":"2023","author":"A S Garcia Moreno","key":"ref158"},{"issue":"04","key":"ref159","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1056\/NEJMoa1512711","article-title":"Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis","volume":"375","author":"K B Gordon","year":"2016","journal-title":"N Engl J Med"},{"issue":"26","key":"ref160","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1056\/NEJMoa1505066","article-title":"Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis","volume":"373","author":"D Baeten","year":"2015","journal-title":"N Engl J Med"},{"issue":"01","key":"ref161","doi-asserted-by":"crossref","first-page":"e001596","DOI":"10.1136\/bmjgast-2024-001596","article-title":"Assessing brodalumab in the treatment of primary sclerosing cholangitis (SABR-PSC pilot study): protocol for a single-arm, multicentre, pilot study","volume":"12","author":"A Elzubeir","year":"2025","journal-title":"BMJ Open Gastroenterol"},{"issue":"02","key":"ref162","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1080\/14740338.2021.1960981","article-title":"Gastroenterological safety of IL-17 inhibitors: a systematic literature review","volume":"21","author":"B Caron","year":"2022","journal-title":"Expert Opin Drug Saf"},{"issue":"05","key":"ref163","doi-asserted-by":"crossref","first-page":"e0233781","DOI":"10.1371\/journal.pone.0233781","article-title":"Risk for development of inflammatory bowel disease under inhibition of interleukin 17: a systematic review and meta-analysis","volume":"15","author":"J Burisch","year":"2020","journal-title":"PLoS One"},{"issue":"12","key":"ref164","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1136\/gutjnl-2011-301668","article-title":"Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial","volume":"61","author":"W Hueber","year":"2012","journal-title":"Gut"},{"issue":"11","key":"ref165","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1038\/ajg.2016.298","article-title":"A randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn's disease","volume":"111","author":"S R Targan","year":"2016","journal-title":"Am J Gastroenterol"},{"key":"ref166","doi-asserted-by":"crossref","first-page":"1124628","DOI":"10.3389\/fphar.2023.1124628","article-title":"IL-17 inhibitor-associated inflammatory bowel disease: a study based on literature and database analysis","volume":"14","author":"Z Deng","year":"2023","journal-title":"Front Pharmacol"},{"issue":"04","key":"ref167","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 clinical trial","volume":"210","author":"L Lancaster","year":"2024","journal-title":"Am J Respir Crit Care Med"},{"issue":"01","key":"ref168","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":"M L Decaris","year":"2021","journal-title":"Respir Res"},{"key":"ref169","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1016\/S0168-8278(24)00606-8","article-title":"LBP-039 Oral alpha-v\/beta-6 and alpha-v\/beta-1 integrin inhibitor bexotegrast in primary sclerosing cholangitis: updated 12-week interim safety and efficacy analysis of the INTEGRIS-PSC phase 2a trial","volume":"80","author":"M Trauner","year":"2024","journal-title":"J Hepatol"},{"volume-title":"Bexotegrast, an oral inhibitor of \u03b1v\u03b26 and \u03b1v\u03b21 integrins, was shown to improve markers and symptoms of cholestasis and stabilized markers of liver fibrosis in participants with primary sclerosing cholangitis: Week 24 results from the Phase 2 INTEGRIS-PSC trial","author":"K V Kowdley","key":"ref170"},{"issue":"11","key":"ref171","doi-asserted-by":"crossref","first-page":"6042","DOI":"10.3390\/ijms25116042","article-title":"Machine learning identifies key proteins in primary sclerosing cholangitis progression and links high CCL24 to cirrhosis","volume":"25","author":"T Snir","year":"2024","journal-title":"Int J Mol Sci"},{"issue":"04","key":"ref173","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1002\/hep.1840130425","article-title":"Biliary tract disease in rats with experimental small bowel bacterial overgrowth","volume":"13","author":"S N Lichtman","year":"1991","journal-title":"Hepatology"},{"issue":"02","key":"ref174","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/0016-5085(91)90224-9","article-title":"Hepatic injury associated with small bowel bacterial overgrowth in rats is prevented by metronidazole and tetracycline","volume":"100","author":"S N Lichtman","year":"1991","journal-title":"Gastroenterology"},{"issue":"04","key":"ref175","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1136\/gutjnl-2015-310500","article-title":"The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls","volume":"66","author":"M Kummen","year":"2017","journal-title":"Gut"},{"issue":"03","key":"ref176","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41575-022-00690-y","article-title":"The microbiota and the gut-liver axis in primary sclerosing cholangitis","volume":"20","author":"J R Hov","year":"2023","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"03","key":"ref177","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/hep.32773","article-title":"A shared mucosal gut microbiota signature in primary sclerosing cholangitis before and after liver transplantation","volume":"77","author":"M J Hole","year":"2023","journal-title":"Hepatology"},{"issue":"06","key":"ref178","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/apt.12232","article-title":"Randomised clinical trial: vancomycin or metronidazole in patients with primary sclerosing cholangitis - a pilot study","volume":"37","author":"J H Tabibian","year":"2013","journal-title":"Aliment Pharmacol Ther"},{"issue":"10","key":"ref179","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/apt.17936","article-title":"Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): a matched analysis from the Paediatric PSC Consortium","volume":"59","author":"A Ricciuto","year":"2024","journal-title":"Aliment Pharmacol Ther"},{"issue":"01","key":"ref180","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1097\/MJT.0000000000000102","article-title":"Prospective clinical trial of rifaximin therapy for patients with primary sclerosing cholangitis","volume":"24","author":"J H Tabibian","year":"2017","journal-title":"Am J Ther"},{"issue":"8040","key":"ref181","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/s41586-024-08095-4","article-title":"Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin","volume":"635","author":"A M Turner","year":"2024","journal-title":"Nature"},{"issue":"01","key":"ref182","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/ajg.2008.14","article-title":"Minocycline in the treatment of patients with primary sclerosing cholangitis: results of a pilot study","volume":"104","author":"M G Silveira","year":"2009","journal-title":"Am J Gastroenterol"},{"issue":"S 02","key":"ref183","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.cmi.2021.09.038","article-title":"European Society of Clinical Microbiology and Infectious Diseases: 2021 update on the treatment guidance document for Clostridioides difficile infection in adults","volume":"27","author":"J van Prehn","year":"2021","journal-title":"Clin Microbiol Infect"},{"issue":"07","key":"ref184","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.14309\/ajg.0000000000000115","article-title":"Fecal microbiota transplantation in patients with primary sclerosing cholangitis: a pilot clinical trial","volume":"114","author":"J R Allegretti","year":"2019","journal-title":"Am J Gastroenterol"},{"issue":"01","key":"ref185","doi-asserted-by":"crossref","first-page":"e095392","DOI":"10.1136\/bmjopen-2024-095392","article-title":"FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial","volume":"15","author":"S Al-Shakhshir","year":"2025","journal-title":"BMJ Open"},{"issue":"03","key":"ref186","doi-asserted-by":"crossref","first-page":"101431","DOI":"10.1016\/j.xcrm.2024.101431","article-title":"The gut microbiome regulates the clinical efficacy of sulfasalazine therapy for IBD-associated spondyloarthritis","volume":"5","author":"S F Lima","year":"2024","journal-title":"Cell Rep Med"},{"issue":"01","key":"ref187","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1038\/s41467-023-39029-9","article-title":"Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis","volume":"14","author":"M Ichikawa","year":"2023","journal-title":"Nat Commun"},{"issue":"07","key":"ref188","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1097\/MEG.0b013e3282f5197e","article-title":"Probiotics in primary sclerosing cholangitis: a randomized placebo-controlled crossover pilot study","volume":"20","author":"F P Vleggaar","year":"2008","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"05","key":"ref189","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1080\/00365521.2019.1611917","article-title":"Efficacy and safety of curcumin in primary sclerosing cholangitis: an open label pilot study","volume":"54","author":"J E Eaton","year":"2019","journal-title":"Scand J 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