Preprint Case Report Version 1 Preserved in Portico This version is not peer-reviewed

A Rare Case of Hepatic Vanishing Bile Duct Syndrome Occurring After Combination Therapy With Nivolumab and Cabozantinib in a Patient With Renal Carcinoma

Version 1 : Received: 18 January 2022 / Approved: 20 January 2022 / Online: 20 January 2022 (11:07:21 CET)

A peer-reviewed article of this Preprint also exists.

Gourari, K.; Catherine, J.; Garaud, S.; Kerger, J.; Lepida, A.; Georgala, A.; Lebrun, F.; Galdon, M.G.; Gil, T.; Willard-Gallo, K.; Fontsa, M.L. A Rare Case of Hepatic Vanishing Bile Duct Syndrome Occurring after Combination Therapy with Nivolumab and Cabozantinib in a Patient with Renal Carcinoma. Diagnostics 2022, 12, 539. Gourari, K.; Catherine, J.; Garaud, S.; Kerger, J.; Lepida, A.; Georgala, A.; Lebrun, F.; Galdon, M.G.; Gil, T.; Willard-Gallo, K.; Fontsa, M.L. A Rare Case of Hepatic Vanishing Bile Duct Syndrome Occurring after Combination Therapy with Nivolumab and Cabozantinib in a Patient with Renal Carcinoma. Diagnostics 2022, 12, 539.

Abstract

Tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) significantly improve the outcomes of patients with advanced clear cell renal cell carcinoma (ccRCC), but high-grade toxicities can occur, particularly during combination therapy. Herein, we report a patient with advanced metastatic ccRCC, who developed grade 4 cholestasis during combined therapy with nivolumab and cabozantinib. After the exclusion of common disorders associated with choles-tasis and a failure of corticosteroids (CS), a liver biopsy was performed that demonstrated severe ductopenia. Consequently, a diagnosis of vanishing bile duct syndrome related to TKI and ICI administration was made, resulting in CS discontinuation and ursodeoxycholic acid administra-tion. After a 7-months follow-up, liver tests had returned to normal values. Immunological studies revealed that our patient had developed robust T-cells and macrophages infiltrates in his lung metastasis, as well as in skin and liver tissues at the onset of toxicities. At the same time, peripheral blood immunophenotyping revealed significant changes in T-cell subsets suggesting their potential role in the pathophysiology of the disease.

Keywords

Checkpoint inhibitors; Immune related adverse events; Cholestasis; Severe ductopenia; Vanishing bile duct syndrome

Subject

Medicine and Pharmacology, Oncology and Oncogenics

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