Pembrolizumab-Induced Vanishing Bile Duct Syndrome: a Case Report


Immune check-point inhibitors (ICPI) are becoming frequently used as first- or second-line therapy in different types of cancer. ICPI-related hepatotoxicity is usually immune mediated and can vary in severity from mild hepatitis to acute liver failure. We report the case of a patient with non-small cell lung cancer who developed severe hepatotoxicity following the first administration of pembrolizumab. Unexpectedly, pathological findings revealed a non-immune-mediated cholestatic liver injury consistent with vanishing bile duct syndrome (VBDS). VBDS is a rare disease characterized by progressive destruction of intrahepatic bile ducts, which has been associated with different conditions, including adverse drug reactions. Treatment consists in discontinuation of the offending drug while steroid-based treatment is not recommended.

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  1. 1.

    Lleo A, Rimassa L, Colombo M. Hepatotoxicity of immune check-point inhibitors: approach and management. Dig Liver Dis. 2019;51:1074–8.

    CAS  Article  Google Scholar 

  2. 2.

    Ardolino L, Joshua A. Immune check-point inhibitors in malignancy. Aust Prescr. 2019;42(2):62–7.

    Article  Google Scholar 

  3. 3.

    Aivazian K, Long GV, Sinclair EC, Kench JG, McKenzie CA. Histopathology of pembrolizumab-induced hepatitis: a case report. Pathology. 2017;49(7):789–92.

    Article  PubMed  Google Scholar 

  4. 4.

    Cheung V, Gupta T, Payne M, Middleton MR, Collier JD, Simmons A, et al. Immunotherapy-related hepatitis: real-world experience from a tertiary centre. Frontline Gastroenterol. 2019;10:364–71.

    CAS  Article  Google Scholar 

  5. 5.

    Kobayashi K, Nakachi I, Mitsuishi A, Arai D, Sakurai K, Masaki K, et al. Successful retreatment using pembrolizumab for nonsmall lung cell cancer after severe immune-related hepatitis: a case report. Clin Lung Cancer. 2020;21(1):e30–2.

    Article  Google Scholar 

  6. 6.

    Forschner A, Schraml C, Pierchalla K, Weide B, Eigentler TK, Lauer UM, et al. Pembrolizumab-induced hepatitis: diagnosis and treatment. J Dtsch Dermatol Ges. 2017;15(9):933–5.

    Article  PubMed  Google Scholar 

  7. 7.

    Reau NS, Jensen DM. Vanishing bile duct syndrome. Clin Liver Dis. 2008;12:203–17.

    Article  Google Scholar 

  8. 8.

    Bakhit M, McCarthy TR, Park S, et al. Vanishing bile duct syndrome in Hodgkin’s lymphoma: a case report and literature review. World J Gastroenterol. 2017;23(2):366–72.

    Article  Google Scholar 

  9. 9.

    Zhong YY, McLean L, Buckle A, Siva S, Tran B. Vanishing bile duct syndrome associated with pazopanib after progression on pembrolizumab. Can J Urol. 2020;27(4):10339–41.

    PubMed  Google Scholar 

  10. 10.

    Visentin M, Lenggenhager D, Gai Z, Kullak-Ublick GA. Drug-induced bile duct injury. Biochim Biophys Acta Mol basis Dis. 1864;2018:1498–506.

    Google Scholar 

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Conception and design of the work: Lleo, Masetti, Pugliese, Finocchiaro, Di Tommaso, Lancellotti.

Drafting and critical revising of the work: Masetti, Pugliese, Lleo, Aghemo, Rimassa.

Final approval of the version to be published: all authors.

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Correspondence to Ana Lleo.

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Masetti, C., Pugliese, N., Rimassa, L. et al. Pembrolizumab-Induced Vanishing Bile Duct Syndrome: a Case Report. SN Compr. Clin. Med. (2021).

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  • Pembrolizumab
  • Cholestasis
  • Hepatotoxicity
  • Immunotherapy