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Cloxacillin-induced acute vanishing bile duct syndrome: a case study and literature review
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  • Kyrillos Faragalla,
  • Helena Lau,
  • Hanlin Wang,
  • Jimin Liu
Kyrillos Faragalla
University of Saskatchewan

Corresponding Author:kfaragal@uwo.ca

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Helena Lau
Halton Healthcare Services
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Hanlin Wang
University of California Los Angeles David Geffen School of Medicine
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Jimin Liu
McMaster University Faculty of Health Sciences
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Abstract

Ductopenia is often regarded as a chronic process where ≥50% of portal tracts lack bile ducts, which is also known as vanishing bile duct syndrome (VBDS). One etiology is drug-induced liver injury. Cloxacillin, an anti-staphylococcal penicillin, typically causes “bland” cholestasis. We present the first case of cloxacillin-induced acute ductopenia or VBDS and a review of published cloxacillin-induced liver injuries. A 66-year-old woman with no prior liver disease, but known penicillin allergy, was treated for post-carotid angioplasty staphylococcal infection with 6 weeks of cloxacillin. She presented with a two-week history of weakness and jaundice. Laboratory work-up showed elevated liver enzymes, hyperbilirubinemia, and eosinophilia. She required ICU transfer for hypotension and was started empirically on prednisone. Liver biopsy revealed severe centrilobular cholestasis, mild necroinflammation, and ductopenia with epithelial injury, but no ductular reaction. Two-months later, she was discharged on hydrocortisone and ursodiol with persistently elevated alkaline phosphatase and bilirubin. She was considered for liver transplantation but died of liver failure four months later. Four additional articles were found with histopathologic descriptions of cloxacillin-related liver injury. These included portal inflammation, cholestasis and mild necroinflammation. Clinical features were reported in two cases; both had mild symptoms with cholestatic liver enzymes and hyperbilirubinemia. Both patients recovered completely within 10-60 days. Cloxacillin-induced cholestasis can be secondary to acute ductopenia, which can result in worse clinical outcomes than previously described “bland” cholestasis. Liver biopsy is recommended to identify cases with acute VBDS.
22 Feb 2022Submitted to British Journal of Clinical Pharmacology
22 Feb 2022Submission Checks Completed
22 Feb 2022Assigned to Editor
03 Mar 2022Reviewer(s) Assigned
01 Apr 2022Review(s) Completed, Editorial Evaluation Pending
07 Apr 2022Editorial Decision: Revise Minor
15 May 20221st Revision Received
16 May 2022Submission Checks Completed
16 May 2022Assigned to Editor
16 May 2022Review(s) Completed, Editorial Evaluation Pending
16 May 2022Reviewer(s) Assigned
07 Jun 2022Editorial Decision: Accept
14 Jul 2022Published in British Journal of Clinical Pharmacology. 10.1111/bcp.15445