Case Report
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2022; 28(28): 3732-3738
Published online Jul 28, 2022. doi: 10.3748/wjg.v28.i28.3732
Delayed immune-related sclerosing cholangitis after discontinuation of pembrolizumab: A case report
Takeshi Tanaka, Arata Sakai, Masahiro Tsujimae, Yasutaka Yamada, Takashi Kobayashi, Atsuhiro Masuda, Yuzo Kodama
Takeshi Tanaka, Arata Sakai, Masahiro Tsujimae, Yasutaka Yamada, Takashi Kobayashi, Atsuhiro Masuda, Yuzo Kodama, Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Hyogo, Japan
Author contributions: All authors contributed to the study conception and design; Tanaka T, Tsujimae M, Yamada Y, and Kobayashi T performed the material preparation, data collection and analysis; Tanaka T wrote the first draft of the manuscript; Sakai A designed the study concept; Masuda A and Kodama Y were involved in study supervision and revised the manuscript; All authors commented on previous versions of the manuscript, read and approved the final manuscript.
Supported by JSPS KAKENHI, No. JP19K07938.
Informed consent statement: Informed consent was obtained from the patient presented in this article.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Arata Sakai, PhD, Doctor, Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Hyogo, Japan.
Received: April 7, 2022
Peer-review started: April 7, 2022
First decision: May 9, 2022
Revised: May 21, 2022
Accepted: June 30, 2022
Article in press: June 30, 2022
Published online: July 28, 2022

Secondary sclerosing cholangitis, characterized by biliary obstruction, can be caused by drugs such as immune checkpoint inhibitors (ICIs). While there a few reports of sclerosing cholangitis after immune checkpoint inhibitor administration, no case has been reported after discontinuation of such drugs.


A 68-year-old man who underwent chemotherapy for lung adenocarcinoma with bone metastasis presented with abdominal pain and fever 4 mo after the final administration of pembrolizumab. Computed tomography revealed thickening of the gallbladder wall and dilatation of the common bile duct. Endoscopic retro-grade cholangiopancreatography revealed an irregularly narrowed intrahepatic bile duct. Biopsy of the bile duct demonstrated that CD8+ T cells were predominant over CD4+ T cells. Liver biopsy showed dominant infiltration of CD8+ T in the portal tract, but onion-skin lesions were not observed. The patient was diagnosed with immune-related sclerosing cholangitis induced by pembrolizumab. Administration of methylprednisolone and endoscopic nasobiliary drainage were performed, but the cholangiography and laboratory test findings did not improve. No further treatment was administered due to disease progression, and the patient was referred for palliative care.


Immune-related sclerosing cholangitis may have a late onset, and such cases occurring after discontinuation of ICIs should be carefully managed.

Keywords: Immune-related adverse events, Sclerosing cholangitis, Delayed immune-related events, Case report

Core Tip: Immune checkpoint inhibitors have become a new standard in cancer treatment, but have often been reported to induce adverse events, called immune-related adverse events (irAEs). Biliary system complications, such as irAEs, remain rare, and the management strategy remains unclear. We present herein, a rare case of delayed immune-related sclerosing cholangitis (SC) after discontinuation of pembrolizumab. Our case emphasizes that immune-related SC can occur later, but the mechanisms have not yet been elucidated. As such, our case contributes to new knowledge in the hopes of being able to establish proper diagnostic criteria and management strategies for similar patients.