{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:25:03Z","timestamp":1791559503118,"version":"4.3.4"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vanishing bile duct syndrome (VBDS) is an uncommon but clinically important form of cholestatic liver injury, defined by progressive loss of intrahepatic bile ducts and persistent cholestasis. Drug-induced liver injury is one of its recognized causes, and antibiotics are among the most frequently implicated agents. Cephalosporin-associated VBDS remains rare, and cefadroxil has been only exceptionally considered in this context.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 72-year-old man developed jaundice and pruritus after completing a 21-day course of cefadroxil for a mild skin infection. Initial liver tests showed a predominantly cholestatic pattern, with marked elevation of gamma-glutamyl transferase and conjugated hyperbilirubinaemia. Viral, autoimmune, and IgG4-related causes were excluded, and magnetic resonance imaging showed no biliary obstruction. As cholestasis persisted despite withdrawal of the suspected drug, liver biopsy was performed and showed intrahepatic cholestasis with bile duct injury and ductopenic features, consistent with VBDS. The patient was treated with ursodeoxycholic acid, with gradual biochemical recovery and subsequent normalization of liver tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This case illustrates a rare but relevant presentation of antibiotic-associated VBDS after cefadroxil exposure. Although cephalosporins are widely used and generally safe, they can exceptionally be associated with clinically significant cholestatic drug-induced liver injury. The diagnosis of VBDS requires careful exclusion of mechanical obstruction, viral hepatitis, autoimmune cholangiopathies, and other systemic causes, and liver biopsy remains central when cholestasis is prolonged or unexplained. Treatment is mainly supportive, centered on withdrawal of the suspected agent and management of cholestasis; ursodeoxycholic acid is frequently used, although responses are variable across reported cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cefadroxil-associated VBDS appears to be a rare manifestation of cholestatic drug-induced liver injury. Clinicians should consider this diagnosis in patients who develop persistent jaundice and pruritus after antibiotic exposure, particularly when imaging is normal and competing causes have been excluded. Early recognition, drug withdrawal, close biochemical follow-up, and timely biopsy in persistent cases are essential to avoid delayed diagnosis of this potentially severe condition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1866580","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:26:34Z","timestamp":1785212794000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cefadroxil-associated cholestatic liver injury presenting as vanishing bile duct syndrome: a case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Jonathan","family":"Soldera","sequence":"first","affiliation":[{"name":"Acute Medicine and Gastroenterology, University of South Wales in association with Learna Ltd","place":["Cardiff, United Kingdom"]},{"name":"Post Graduation Program in Pathology, Universidade Federal de Ci\u00eancias da Sa\u00fade de Porto Alegre (UFCSPA)","place":["Porto Alegre, Brazil"]},{"name":"Department of Gastroenterology, Logan Hospital","place":["Brisbane, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Salgado","sequence":"additional","affiliation":[{"name":"Post Graduation Program in Pathology, Universidade Federal de Ci\u00eancias da Sa\u00fade de Porto Alegre (UFCSPA)","place":["Porto Alegre, Brazil"]},{"name":"ICAP Pathology","place":["Caxias do Sul, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref1","volume-title":"LiverTox: Clinical and Research Information on Drug-Induced Liver Injury","year":"2012"},{"key":"ref2","volume-title":"LiverTox: Clinical and Research Information on Drug-Induced Liver Injury","year":"2012"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.3390\/jcm11123253","article-title":"Vanishing bile duct syndrome in an adult patient: case report and review of the literature","volume":"11","author":"Izzo","year":"2022","journal-title":"J Clin Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/s0168-8278(05)80476-3","article-title":"Antibiotic-associated acute vanishing bile duct syndrome: a pattern associated with severe, prolonged, intrahepatic cholestasis","volume":"20","author":"Davies","year":"1994","journal-title":"J Hepatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1007\/s15010-023-02132-6","article-title":"Antibiotic-associated vanishing bile duct syndrome: a real-world retrospective and pharmacovigilance database analysis","volume":"52","author":"Wang","year":"2023","journal-title":"Infection"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"102015","DOI":"10.1016\/j.clinre.2022.102015","article-title":"Vanishing bile duct syndrome after drug-induced liver injury","volume":"46","author":"Wasuwanich","year":"2022","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"300060520937842","DOI":"10.1177\/0300060520937842","article-title":"Meropenem-induced vanishing bile duct syndrome: a case report","volume":"48","author":"Zubarev","year":"2020","journal-title":"J Int Med Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1592\/phco.30.9.953","article-title":"Meropenem-induced vanishing bile duct syndrome","volume":"30","author":"Schumaker","year":"2010","journal-title":"Pharmacotherapy"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e8009","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":"Medicine (Baltimore)"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e32262","DOI":"10.7759\/cureus.32262","article-title":"Severe Cholestatic drug-induced liver injury with cephalosporin use","volume":"14","author":"Yang","year":"2022","journal-title":"Cureus"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/j.1742-7843.2009.00474.x","article-title":"Vanishing bile duct syndrome associated with azithromycin in a 62-year-old man","volume":"106","author":"Juricic","year":"2010","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"4633","DOI":"10.1111\/bcp.15445","article-title":"Cloxacillin-induced acute vanishing bile duct syndrome: a case study and literature review","volume":"88","author":"Faragalla","year":"2022","journal-title":"Br J Clin Pharmacol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1007\/s12328-019-01022-5","article-title":"Vanishing bile duct syndrome arising in a patient with HIV infection sequentially treated with trimethoprim\/sulfamethoxazole and dapsone","volume":"13","author":"Kathi","year":"2020","journal-title":"Clin J Gastroenterol"},{"key":"ref14","first-page":"167","article-title":"Trimethoprim-sulfamethoxazole-induced vanishing bile duct syndrome","volume":"92","author":"Yao","year":"1997","journal-title":"Am J Gastroenterol"},{"key":"ref15","first-page":"1230","article-title":"Cholestatic liver disease with ductopenia (vanishing bile duct syndrome) after administration of clindamycin and trimethoprim-sulfamethoxazole","volume":"89","author":"Altraif","year":"1994","journal-title":"Am J Gastroenterol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1097\/00042737-200211000-00019","article-title":"Vanishing bile duct syndrome associated with elevated pancreatic enzymes after short-term administration of amoxicillin","volume":"14","author":"Schwarze","year":"2002","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1097\/01.mpg.0000178086.44155.73","article-title":"Vanishing bile duct syndrome: amoxicillin-clavulanic acid associated intra-hepatic cholestasis responsive to ursodeoxycholic acid","volume":"41","author":"Smith","year":"2005","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1055\/s-0034-1375964","article-title":"Severe ductopenia and cholestasis from levofloxacin drug-induced liver injury: a case report and review","volume":"34","author":"Levine","year":"2014","journal-title":"Semin Liver Dis"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"223","DOI":"10.3109\/00313029309066576","article-title":"Flucloxacillin induced liver disease: histopathological findings at biopsy and autopsy","volume":"25","author":"Eckstein","year":"1993","journal-title":"Pathology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1097\/MCG.0b013e3181a51af9","article-title":"Moxifloxacin associated vanishing bile duct syndrome","volume":"44","author":"Robinson","year":"2010","journal-title":"J Clin Gastroenterol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"5490","DOI":"10.12998\/wjcc.v9.i20.5490","article-title":"Herb-induced liver injury: systematic review and meta-analysis","volume":"9","author":"Ballotin","year":"2021","journal-title":"World J Clin Cases"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1002\/hep.28967","article-title":"Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements","volume":"65","author":"Bonkovsky","year":"2017","journal-title":"Hepatology"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1002\/hep.1840200610","article-title":"Chlorpromazine-induced vanishing bile duct syndrome leading to biliary cirrhosis","volume":"20","author":"Moradpour","year":"1994","journal-title":"Hepatology"},{"key":"ref24","first-page":"1038","article-title":"Cholestasis secondary to Hodgkin's disease: report of 2 cases of vanishing bile duct syndrome","volume":"83","author":"de Medeiros","year":"1998","journal-title":"Haematologica"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1097\/MEG.0b013e3282b9e6c2","article-title":"Severe jaundice, due to vanishing bile duct syndrome, as presenting symptom of Hodgkin's lymphoma, fully reversible after chemotherapy","volume":"20","author":"Leeuwenburgh","year":"2008","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"ref26","first-page":"1456","article-title":"Drug-induced vanishing bile duct syndrome: response to ursodiol","volume":"91","author":"O'Brien","year":"1996","journal-title":"Am J Gastroenterol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"117573","DOI":"10.12998\/wjcc.v14.i4.117573","article-title":"Mixed hepatocellular-cholestatic liver injury from cefepime: a case report","volume":"14","author":"Garcia","year":"2026","journal-title":"World J Clin Cases"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1111\/apt.70284","article-title":"Clinical and genetic associations in cephalosporin-induced liver injury: insights from the drug-induced liver injury network","volume":"62","author":"Vuppalanchi","year":"2025","journal-title":"Aliment Pharmacol Ther"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"120","DOI":"10.4254\/wjh.v16.i2.120","article-title":"Insights into skullcap herb-induced liver injury","volume":"16","author":"Soldera","year":"2024","journal-title":"World J Hepatol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"867","DOI":"10.4254\/wjh.v16.i6.867","article-title":"Immunological crossroads: the intriguing dance between hepatitis C and autoimmune hepatitis","volume":"16","author":"Soldera","year":"2024","journal-title":"World J Hepatol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"29","DOI":"10.21037\/dmr-22-83","article-title":"Post-COVID-19 cholangiopathy","volume":"6","author":"Graciolli","year":"2023","journal-title":"Dig Med Res"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.3390\/diagnostics16121821","article-title":"Autoimmune hepatitis induced by immune checkpoint inhibitors in adults: a systematic review","volume":"16","author":"Chonat","year":"2026","journal-title":"Diagnostics"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"4075","DOI":"10.12998\/wjcc.v8.i18.4075","article-title":"Primary sclerosing cholangitis and autoimmune hepatitis overlap syndrome associated with inflammatory bowel disease: a case report and systematic review","volume":"8","author":"Ballotin","year":"2020","journal-title":"World J Clin Cases"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.4240\/wjgs.v15.i10.2305","article-title":"Hepatobiliary tuberculosis in the developing world","volume":"15","author":"Esguerra-Paculan","year":"2023","journal-title":"World J Gastrointest Surg"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"151","DOI":"10.13105\/wjma.v11.i5.151","article-title":"Pulmonary cytomegalovirus infection: a case report and systematic review","volume":"11","author":"Kanika","year":"2023","journal-title":"World J Meta-Anal"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"101481","DOI":"10.4291\/wjgp.v16.i1.101481","article-title":"Evaluation of biological therapies in autoimmune hepatitis: a case-based systematic review","volume":"16","author":"Eldew","year":"2025","journal-title":"World J Gastrointest Pathophysiol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"302","DOI":"10.3855\/jidc.16983","article-title":"Haemophagocytic lymphohistiocytosis following a COVID-19 infection: case report","volume":"17","author":"Soldera","year":"2023","journal-title":"J Infect Dev Ctries"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"296","DOI":"10.5662\/wjm.v13.i4.296","article-title":"Post-COVID-19 cholangiopathy: systematic review","volume":"13","author":"Rasheed","year":"2023","journal-title":"World J Methodol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.3390\/diagnostics16101548","article-title":"Beyond the tipping point: advances in the diagnosis and Management of Acute-on-Chronic Liver Failure and end-Stage Liver Disease","volume":"16","author":"Soldera","year":"2026","journal-title":"Diagnostics"},{"key":"ref40","first-page":"e24065","article-title":"Performance of six predictive models of death of patients hospitalized for decompensated cirrhosis: a multicenter study","volume":"62","author":"Brand\u00e3o","year":"2025","journal-title":"Arq Gastroenterol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1866580\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T04:26:36Z","timestamp":1785212796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1866580\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":40,"alternative-id":["10.3389\/fmed.2026.1866580"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1866580","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]},"article-number":"1866580"}}