{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:00:40Z","timestamp":1792839640114,"version":"4.5.0"},"reference-count":95,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Secondary sclerosing cholangitis (SSC), is one of the phenotypes of DILI first described in the 1980s. Check point inhibitors (CPIs) are currently the most frequent cause of SCC. Aims: To describe the epidemiology, clinical and biochemical features at presentation, differential diagnoses, pathophysiology, imaging, histological characteristics and management associated with SSC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>A language and date\u2010unrestricted Medline literature search was conducted to identify case reports and clinical series on SSC with special emphasis on CPIs (2007\u20102023).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 19 different drugs that have been shown to induce SSC. A total of 64 cases with SSC due to CPIs are presented. This was mostly seen in patients treated with anti\u2010Programmed cell death (PD)\u20101\/PD\u2010L1 inhibitors. The most frequent presenting signs and symptoms were abdominal pain and jaundice. Large\u2010duct cholangitis induced by CPIs is a very rare condition while small\u2010duct cholangitis is more common. Nivolumab and pembrolizumab were the most commonly implicated agents. Biopsies have revealed predominant CD8+ T cell infiltration in biliary strictures. Corticosteroids is linked to a low frequency of success and is the only agent recommended to begin the treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CPIs\u2010induced SSC seems to affect the entire biliary system. Clinicians should consider and suspect SSC when a probable CPIs\u2010induced hepatitis does not respond to corticosteroids. Additionally, further randomized, controlled trials should prospectively investigate alternative therapies for treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.16163","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T07:09:27Z","timestamp":1733123367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Secondary Sclerosing Cholangitis due to Drugs With a Special Emphasis on Checkpoint Inhibitors"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8392-0632","authenticated-orcid":false,"given":"Einar S.","family":"Bjornsson","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of Iceland  Reykjav\u00edk Iceland"},{"name":"Department of Internal Medicine, Division of Gastroenterology Landspitali University Hospital Reykjavik  Reykjav\u00edk Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiana","family":"Arnedillo","sequence":"additional","affiliation":[{"name":"Hospital Provincial del Centenario  Rosario Argentina"},{"name":"Facultad de Ciencias M\u00e8dicas National University of Rosario School of Medicine  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8569-8123","authenticated-orcid":false,"given":"Fernando","family":"Bessone","sequence":"additional","affiliation":[{"name":"Hospital Provincial del Centenario  Rosario Argentina"},{"name":"Facultad de Ciencias M\u00e8dicas National University of Rosario School of Medicine  Rosario Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.10.011"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004836-198612000-00022"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840090209"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00571690"},{"key":"e_1_2_15_6_1","first-page":"1302","article-title":"Extrahepatic Biliary Stenoses After Hepatic Arterial Infusion (HAI) of Floxuridine (FUdR) for Liver Metastases From Colorectal Cancer","volume":"48","author":"Aldrighetti L.","year":"2001","journal-title":"Hepato\u2010Gastroenterology"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crad.2005.01.006"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crad.2006.02.013"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.485"},{"key":"e_1_2_15_10_1","first-page":"e52","article-title":"Cholestasis and Biliary Dilatation Associated With Chronic Ketamine Abuse: A Case Series","volume":"52","author":"Lo R. S.","year":"2011","journal-title":"Singapore Medical Journal"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26459"},{"issue":"78","key":"e_1_2_15_12_1","first-page":"e1","article-title":"Ketamine\u2010Induced Cholangiopathy","volume":"20","author":"Lui K. L.","year":"2014","journal-title":"Hong Kong Medical Journal"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-015-3914-3"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31650"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13256-024-04421-6"},{"issue":"5","key":"e_1_2_15_16_1","first-page":"888","article-title":"A Case of Secondary Sclerosing Cholangitis Caused by Chemotherapy With Nab\u2010Paclitaxel","volume":"112","author":"Matsuo T.","year":"2015","journal-title":"Nihon Shokakibyo Gakkai Zasshi"},{"issue":"3","key":"e_1_2_15_17_1","first-page":"173","article-title":"Aitor Odriozola Herr\u00e1n V\u00edctor Jos\u00e9 Echavarr\u00eda Rodr\u00edguez, Sara Alonso Fern\u00e1ndez Secondary Sclerosing Cholangitis Induced by Systemic Chemotherapy","volume":"116","author":"Ant\u00f3n \u00c1","year":"2024","journal-title":"Revista Espa\u00f1ola de Enfermedades Digestivas"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2015.03.002"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.13986"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.2147\/HMER.S384220"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.06.035"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000398"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1465"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2017-000268"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdw649"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-017-0453-0"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000366"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2017.10.007"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14136"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-017-2062-3"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-0640-2392"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2018.09.016"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000496933"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13329"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2019-232505"},{"key":"e_1_2_15_37_1","article-title":"Clinical Features of Liver Injury Induced by Immune Checkpoint Inhibitors in Japanese Patients","author":"Imoto K.","year":"2019","journal-title":"Canadian Journal of Gastroenterology and Hepatology"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.2591-18"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2019-0121"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-0948-1271"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro-2018-101146"},{"key":"e_1_2_15_42_1","first-page":"439","article-title":"Nivolumab\u2010Induced Cholangitis in Patients With Non\u2010Small Cell Lung cancer: Case Series and a Review of Literature","volume":"11","author":"Izumi H.","year":"2019","journal-title":"Molecular and Clinical Oncology"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2019-0077"},{"key":"e_1_2_15_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2019.04.023"},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.04.022"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30189"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.11.021"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.1981-18"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.2330-18"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14000"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgast-2020-000487"},{"key":"e_1_2_15_52_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v26.i3.353"},{"key":"e_1_2_15_53_1","doi-asserted-by":"publisher","DOI":"10.1159\/000507695"},{"key":"e_1_2_15_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-020-01677-9"},{"key":"e_1_2_15_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/rcr2.560"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12328-020-01178-5"},{"key":"e_1_2_15_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmcr.2020.101197"},{"key":"e_1_2_15_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12328-020-01218-0"},{"key":"e_1_2_15_59_1","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/goz044"},{"key":"e_1_2_15_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2020.100270"},{"key":"e_1_2_15_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2020.09.007"},{"key":"e_1_2_15_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12328-020-01287-1"},{"key":"e_1_2_15_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-021-01136-z"},{"key":"e_1_2_15_64_1","doi-asserted-by":"publisher","DOI":"10.21037\/apm-21-858"},{"key":"e_1_2_15_65_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000025774"},{"key":"e_1_2_15_66_1","first-page":"P820","article-title":"A Case of Steroid Responsive Nivolumab Induced Cholangitis","volume":"54","author":"Kynaston A.","year":"2022","journal-title":"Pathology RCPA"},{"key":"e_1_2_15_67_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v28.i28.3732"},{"key":"e_1_2_15_68_1","first-page":"1652","article-title":"Gastrointestinal: Immune\u2010related sclerosing cholangitis with pembrolizumab: Imaging and histological features","volume":"37","author":"Suzuki N.","year":"2022","journal-title":"Revista de Gastroenterolog\u00eda y Hepatolog\u00eda"},{"issue":"1","key":"e_1_2_15_69_1","first-page":"182","article-title":"Pembrolizumab Induced Sclerosing Cholangitis: Why You Need a Liver Biopsy","volume":"16","author":"Liang I.","year":"2023","journal-title":"Case Reports in Oncology"},{"issue":"10","key":"e_1_2_15_70_1","article-title":"Concurrent Nivolumab\u2010Induced Gastritis and Cholangitis Accompanied by Biliary Tract Hemorrhage in a Patient With Stage IV Lung Adenocarcinoma","volume":"15","author":"Tsukaguchi A.","year":"2023","journal-title":"Cureus"},{"key":"e_1_2_15_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.11.036"},{"key":"e_1_2_15_72_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15340"},{"key":"e_1_2_15_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2023.07.006"},{"key":"e_1_2_15_74_1","doi-asserted-by":"publisher","DOI":"10.2147\/CEG.S115518"},{"key":"e_1_2_15_75_1","doi-asserted-by":"publisher","DOI":"10.1097\/MJT.0b013e3181c9dac6"},{"key":"e_1_2_15_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21685"},{"key":"e_1_2_15_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.05.011"},{"key":"e_1_2_15_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxac.2023.02.001"},{"key":"e_1_2_15_79_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs0820169"},{"key":"e_1_2_15_80_1","first-page":"106","article-title":"A Novel Pathologic Marker, Indoleamine 2,3\u2010Dioxygenase 1, for the Cholangiopathy of Immune Checkpoint Inhibitors\u2010Induced Immune Mediated Hepatotoxicity as Adverse Events and the Prediction of Additional Ursodeoxycholic Acid Treatment. Medical Molecular","volume":"56","author":"Yoshimura K.","year":"2023","journal-title":"Morphology"},{"key":"e_1_2_15_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00261\u2010022\u201003551\u2010z"},{"key":"e_1_2_15_82_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.sult.2022.06.007"},{"key":"e_1_2_15_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-00653-1"},{"key":"e_1_2_15_84_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000002280"},{"key":"e_1_2_15_85_1","first-page":"1","article-title":"Navigating the Liver Landscape: Upcoming Pharmacotherapies for Primary Sclerosing Cholangitis","volume":"31","author":"Pham H. N.","year":"2024","journal-title":"Expert Opinion on Pharmacotherapy"},{"key":"e_1_2_15_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-017-0583-8"},{"key":"e_1_2_15_87_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v14.i7.1269"},{"key":"e_1_2_15_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2022.12.008"},{"key":"e_1_2_15_89_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0013-y"},{"key":"e_1_2_15_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100719"},{"key":"e_1_2_15_91_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005635"},{"key":"e_1_2_15_92_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx225"},{"key":"e_1_2_15_93_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2019.0013"},{"key":"e_1_2_15_94_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000045"},{"key":"e_1_2_15_95_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0044-1779520"},{"key":"e_1_2_15_96_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20110184"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.16163","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.16163","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.16163","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:36:05Z","timestamp":1772973365000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.16163"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,2]]},"references-count":95,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/liv.16163"],"URL":"https:\/\/doi.org\/10.1111\/liv.16163","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,2]]},"assertion":[{"value":"2024-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e16163"}}