• Yuya Hirasawa, Kiyoshi Yoshimura, Hiroto Matsui, Yutaro Kubota, Hiroo Ishida, Jun Arai, Masashi Sakaki, Nao Oguro, Midori Shida, Makoto Taniguchi, Kazuyuki Hamada, Hirotsugu Ariizumi, Tomoyuki Ishiguro, Ryotaro Ohkuma, Takehiko Sambe, Atsushi Horiike, Chiyo K Imamura, Eisuke Shiozawa, Satoshi Wada, Junji Tsurutani, Sanju Iwamoto, Naoki Uchida, Yuji Kiuchi, Genshu Tate, Shinichi Kobayashi, and Takuya Tsunoda.
• Division of Medical Oncology, Department of Medicine, Showa University School of Medicine.
• Medicine (Baltimore). 2021 Jun 11; 100 (23): e25774e25774.

IntroductionImmune checkpoint inhibitors (ICIs), particularly anti-PD-1 antibody, have dramatically changed cancer treatment; however, fatal immune-related adverse events (irAEs) can develop. Here, we describe a severe case of sclerosing cholangitis-like irAE. We report the use of 3 immunosuppressive agents that resulted in the death of the patient due to treatment inefficacy. According to a postmarketing study of nivolumab, the frequency of ICI-related sclerosing cholangitis is 0.27% and that of ICI-related cholangitis is 0.20%. There have been 4 case reports of sclerosing cholangitis-like irAE, with imaging findings, including typical intrahepatic bile duct beaded constriction in primary sclerosing cholangitis. Treatment starts with prednisolone and is combined with an immunosuppressant in refractory cases. There are no reports of severe cases that ultimately led to death.Patients ConcernsThe patient is a 64-year-old male with Stage IV squamous cell lung carcinoma; he was hospitalized with abdominal pain and elevation of aspartate transaminase and alanine transaminase, approximately 4 months after ICI administration was suspended. This occurred because the patient treated with nivolumab as the second-line chemotherapy and developed type 1 diabetes mellitus after 11 courses.DiagnosisA grade 3 increase in bilirubin was observed and he was diagnosed with sclerosing cholangitis, based on magnetic resonance cholangiopancreatography imaging and pathological findings of the liver and bile duct.InterventionsPrednisolone, mycophenolate mofetil, and tacrolimus combination therapy was administered.OutcomesThe treatment was difficult and failed. He died from liver failure 8 months after diagnosis. In this case, hepatitis and cholangitis, mainly alanine transaminase-dominant liver disorder, developed in the early stages of irAEs. Although he showed some improvement after prednisolone administration, bilirubin levels began rising again, and sclerosing cholangitis did not improve even with the use of 3 immunosuppressive agents recommended by the ESMO Clinical Practice Guidelines for immune-related hepatotoxicity management. Although the antitumor effect showed a complete response, liver failure led to death.ConclusionThis is the first case report on the ineffectiveness of triple immunosuppressant combination therapy recommended by the guidelines for immune-related hepatotoxicity. It is necessary to develop more appropriate treatment for severe sclerosing cholangitis-like irAE based on the robust evidence.Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

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