{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:13:57Z","timestamp":1793121237161,"version":"4.5.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Vanishing bile duct syndrome (VBDS) is a rare but potentially fatal cause of intrahepatic cholestasis, usually associated with autoimmune, infectious or drug-induced etiologies. We present the first documented case of VBDS induced by Atezolizumab, an immune checkpoint inhibitor approved as adjuvant therapy in resected stage II-IIIA non-small cell lung cancer. A 63-year-old man developed cholestatic liver injury after three cycles of Atezolizumab, with progressive jaundice and elevated bilirubin despite immunosuppressive therapy. The diagnosis was confirmed by liver biopsy, which revealed intrahepatic bile duct leakage in more than 50% of the portal tracts. Despite initial stabilization, the patient\u2019s bilirubin levels continued to rise and liver transplantation was contraindicated. He was discharged with immunosuppressive and supportive treatment, under close follow-up. This case highlights the need for greater clinical awareness of rare immunotherapy-associated immune-mediated hepatotoxicities, and underlines the importance of histological confirmation in severe or atypical presentations.<\/jats:p>","DOI":"10.3389\/fonc.2025.1637847","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:13:49Z","timestamp":1757564029000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Atezolizumab-induced vanishing bile duct syndrome: a case report"],"prefix":"10.3389","volume":"15","author":[{"given":"Carlos Tom\u00e1s","family":"Noblejas Quiles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Mac\u00edas Cerrolaza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier David","family":"Benitez Fuentes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"L\u00f3pez G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"S\u00e1nchez C\u00e1novas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Nevado Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Mart\u00edn Casc\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Vigueras Campuzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asunci\u00f3n","family":"Chaves Benito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio David","family":"L\u00e1zaro S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"B1","unstructured":"Surveillance, epidemiology and end results program\n          \n          \n          Cancer Stat Facts: Lung and Bronchus"},{"key":"B2","unstructured":"Las cifras del c\u00e1ncer en Espa\u00f1a\n          \n          \n          \n          2024"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ccm.2019.10.001","article-title":"Lung cancer 2020: epidemiology, etiology, and prevention","volume":"41","author":"Bade","year":"2020","journal-title":"Clin Chest Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.07.001","article-title":"Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial","volume":"34","author":"Felip","year":"2023","journal-title":"Ann Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3390\/antib13030056","article-title":"Immune-related adverse events associated with atezolizumab: insights from real-world pharmacovigilance data","volume":"13","author":"Frey","year":"2024","journal-title":"Antibodies (Basel)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.907591","article-title":"Immune-mediated hepatitis during immune checkpoint inhibitor cancer immunotherapy: lessons from autoimmune hepatitis and liver immunology","volume":"13","author":"Hercun","year":"2022","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.rgmx.2023.12.003","article-title":"Hepatitis inmunomediada: conceptos b\u00e1sicos y tratamiento","volume":"89","author":"Velarde-Ruiz Velasco","year":"2024","journal-title":"Rev Gastroenterolog\u00eda M\u00e9xico"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.3390\/medicina60091422","article-title":"Atezolizumab-induced ulcerative colitis in patient with hepatocellular carcinoma: case report and literature review","volume":"60","author":"Kim","year":"2024","journal-title":"Medicina (Kaunas)"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.10.006","article-title":"EASL clinical practice guidelines: liver transplantation","volume":"64","year":"2016","journal-title":"J Hepatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9610(75)90362-1","article-title":"Spectrum of cholangitis","volume":"130","author":"Saik","year":"1975","journal-title":"Am J Surg"},{"key":"B11","volume-title":"En LiverTox: Clinical and Research Information on Drug-Induced Liver Injury","year":"2016"},{"key":"B12","volume-title":"En LiverTox: Clinical and Research Information on Drug-Induced Liver Injury","year":"2016"},{"key":"B13","volume-title":"En LiverTox: Clinical and Research Information on Drug-Induced Liver Injury","year":"2016"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-101-5-635","article-title":"Prolonged intrahepatic cholestasis secondary to acute hepatitis A","volume":"101","author":"Gordon","year":"1984","journal-title":"Ann Intern Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2006.00416.x","article-title":"Epidemiology and clinical features of sporadic hepatitis E as compared with hepatitis A","volume":"101","author":"Chau","year":"2006","journal-title":"Am J Gastroenterol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.52784\/issn.2711-2330","article-title":"Art\u00edculo de revisi\u00f3n: colangitis esclerosante primaria","volume":"2","author":"Almanza-Hurtado","year":"2021","journal-title":"Hepatolog\u00eda"},{"key":"B17","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.gastro-hep.2010.02.006","article-title":"Colangitis esclerosante primaria: diagn\u00f3stico y pron\u00f3stico","volume":"34","author":"Par\u00e9s","year":"2011","journal-title":"Gastroenterol Hepatol"},{"key":"B18","first-page":"1","article-title":"Colangitis (ex-cirrosis) biliar primaria","volume-title":"Tratado de medicina","author":"Pariente","year":"2021"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0057","article-title":"NCCN guidelines\u00ae insights: management of immunotherapy-related toxicities, Version 2.2024","volume":"22","author":"Thompson","year":"2024","journal-title":"J Natl Compr Canc Netw"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1157\/13074061","article-title":"Recuperaci\u00f3n ductular en el s\u00edndrome de los conductillos biliares evanescentes en paciente con linfoma de Hodgkin","volume":"28","author":"C\u00f3rdoba Iturriagagoitia","year":"2005","journal-title":"Gastroenterol Hepatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000008009","article-title":"Acute vanishing bile duct syndrome after therapy with cephalosporin, metronidazole, and clotrimazole: A case report","volume":"96","author":"Zhao","year":"2017","journal-title":"Med (Baltimore)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2007.11.007","article-title":"Vanishing bile duct syndrome","volume":"12","author":"Reau","year":"2008","journal-title":"Clin Liver Dis"},{"key":"B23","article-title":"Caso anatomocl\u00ednico: s\u00edndrome de los conductos biliares evanescentes","volume":"39","author":"Trejo Estrada","year":"1996","journal-title":"Rev Fac Med UNAM"},{"key":"B24","volume-title":"En LiverTox: Clinical and Research Information on Drug-Induced Liver Injury","year":"2019"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2021-0078","article-title":"Vanishing bile duct syndrome following pembrolizumab infusion: case report and review of the literature","volume":"14","author":"Gemelli","year":"2022","journal-title":"Immunotherapy"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s42399-021-00803-9","article-title":"Pembrolizumab-induced vanishing bile duct syndrome: a case report","volume":"3","author":"Masseti","year":"2021","journal-title":"SN Compr Clin Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1159\/000507695","article-title":"Fatal cholestasic liver injury during treatment with PD1 immune checkpoint inhibitor for Malignant melanoma: a case report","volume":"13","author":"Thorsteindottir","year":"2020","journal-title":"Case Rep Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2017-000268","article-title":"Severe steroid-resistant anti-PD1 T-cell checkpoint inhibitor-induced hepatotoxicity driven by biliary injury","volume":"2","author":"Doherty","year":"2017","journal-title":"ESMO Open"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(88)80482-3","article-title":"Idiopathic adulthood ductopenia. A cause of chronic cholestatic liver disease and biliary cirrhosis","volume":"7","author":"Ludwig","year":"1988","journal-title":"J Hepatol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1097\/MCG.0000000000000548","article-title":"Vanishing bile duct syndrome in Hodgkin\u2019s lymphoma: A single center experience and clinical pearls","volume":"50","author":"Bakhit","year":"2016","journal-title":"J Clin Gastroenterol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.0057","article-title":"Neoadjuvant chemoimmunotherapy for NSCLC: A systematic review and meta-analysis","volume":"10","author":"Sorin","year":"2024","journal-title":"JAMA Oncol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1007\/s00262-024-03869-1","article-title":"Differences in immune-related toxicity between PD-1 and PD-L1 inhibitors: a retrospective cohort study in patients with advanced cancer","volume":"74","author":"Ladjevardi","year":"2024","journal-title":"Cancer Immunol Immunother"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2021.08.1994","article-title":"Early and locally advanced non-small-cell lung cancer: an update of the ESMO Clinical Practice Guidelines focusing on diagnosis, staging and systemic and local therapy","volume":"32","author":"Remon","year":"2021","journal-title":"Ann Oncol"},{"key":"B34","first-page":"1","article-title":"Non-small cell lung cancer, version 7.2025, NCCN clinical practice guidelines in oncology","author":"Riely","year":"2025","journal-title":"J\u00a0Natl Compr Canc Netw"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1637847\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:13:51Z","timestamp":1757564031000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1637847\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":34,"alternative-id":["10.3389\/fonc.2025.1637847"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1637847","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]},"article-number":"1637847"}}