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A case with life-threatening secondary sclerosing cholangitis caused by nivolumab

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Abstract

Immune checkpoint inhibitor (ICI) therapy has potent anti-cancer effects but is associated with immune-related adverse events (irAEs). We present a case who developed secondary sclerosing cholangitis following treatment with nivolumab for non-small cell lung cancer who did not respond to immunosuppressive treatments and died of liver failure. A 75 year-old male with lung cancer who had been treated with nivolumab for non-small cell lung cancer developed Grade 3 liver injury with significant elevation of hepatobiliary enzymes. Magnetic resonance cholangiopancreatography (MRCP) revealed diffuse dilatation of the common bile duct and multifocal stenosis with prestenotic dilatation from the perihilar to intrahepatic bile duct, consistent with sclerosing cholangitis. Histological findings represented an infiltration of mainly CD8-positive T cells around the bile ducts in the liver. Despite treatments with ursodeoxycholic acid, prednisolone, and mycophenolate mofetil, the sclerosing cholangitis did not improve, and the patient died due to liver failure and aggravation of lung cancer. These findings suggest that immune checkpoint inhibitors may lead to resistance to immunosuppressive treatment as well as pose a risk of life-threatening sclerosing cholangitis.

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Acknowledgements

We thank Nobuko Yokoyama and Emi Nishio for clerical assistance. This research is partially supported by research funding from the Research Program on Hepatitis from the Japan Agency for Medical Research and Development, AMED (Grant Number: 19fk0210020h0003).

Funding

The study was supported in part by research funding from the Research Program on Hepatitis from the Japan Agency for Medical Research and Development, AMED (Grant Number: 19fk0210020h0003).

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Authors and Affiliations

  1. Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan

    Yuki Yoshikawa, Michio Imamura, Kenji Yamaoka, Yumi Kosaka, Eisuke Murakami, Kei Morio, Hatsue Fujino, Takashi Nakahara, Masami Yamauchi, Tomokazu Kawaoka, Akira Hiramatsu, Clair Nelson Hayes, Hiroshi Aikata & Kazuaki Chayama

  2. Research Center for Hepatology and Gastroenterology, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Yuki Yoshikawa, Michio Imamura, Kenji Yamaoka, Yumi Kosaka, Eisuke Murakami, Kei Morio, Hatsue Fujino, Takashi Nakahara, Masami Yamauchi, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Clair Nelson Hayes, Hiroshi Aikata & Kazuaki Chayama

  3. Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan

    Wataru Okamoto

  4. Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan

    Masataka Tsuge

  5. Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan

    Kazunori Fujitaka & Noboru Hattori

  6. Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan

    Kouji Arihiro

  7. RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Kazuaki Chayama

Authors
  1. Yuki Yoshikawa
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  2. Michio Imamura
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  3. Kenji Yamaoka
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  7. Hatsue Fujino
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  18. Noboru Hattori
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  19. Kazuaki Chayama
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Corresponding author

Correspondence to Kazuaki Chayama.

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Conflict of interest

Michio Imamura has received research funding from Bristol-Myers Squibb and AbbVie. Hiroshi Aikata has received honoraria from Eisai and Bayer. Kazuaki Chayama has received honoraria from Bristol-Myers Squibb and MSD K.K., AbbVie, Gilead Science, Dainippon Sumitomo Pharma and Mitsubishi Tanabe Pharma and research funding from Gilead Science, Dainippon Sumitomo Pharma, MSD K.K., AbbVie, Eisai, TORAY, Otsuka Pharma, Chugai Pharma, Takeda Pharma and Roche.

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All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Informed consent was obtained from all patients for being included in the study.

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Yoshikawa, Y., Imamura, M., Yamaoka, K. et al. A case with life-threatening secondary sclerosing cholangitis caused by nivolumab. Clin J Gastroenterol 14, 283–287 (2021). https://doi.org/10.1007/s12328-020-01287-1

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  • DOI: https://doi.org/10.1007/s12328-020-01287-1

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