Cargando…

Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review

BACKGROUND: Programmed cell death-1 (PD-1) inhibitor has been indicated for many types of malignancies. However, these inhibitors also cause immune-related adverse events. Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%–4.5% of patients treated with PD-1 inhibitors...

Descripción completa

Detalles Bibliográficos
Autores principales: Onoyama, Takumi, Takeda, Yohei, Yamashita, Taro, Hamamoto, Wataru, Sakamoto, Yuri, Koda, Hiroki, Kawata, Soichiro, Matsumoto, Kazuya, Isomoto, Hajime
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969883/
https://www.ncbi.nlm.nih.gov/pubmed/31988594
http://dx.doi.org/10.3748/wjg.v26.i3.353
_version_ 1783489402491633664
author Onoyama, Takumi
Takeda, Yohei
Yamashita, Taro
Hamamoto, Wataru
Sakamoto, Yuri
Koda, Hiroki
Kawata, Soichiro
Matsumoto, Kazuya
Isomoto, Hajime
author_facet Onoyama, Takumi
Takeda, Yohei
Yamashita, Taro
Hamamoto, Wataru
Sakamoto, Yuri
Koda, Hiroki
Kawata, Soichiro
Matsumoto, Kazuya
Isomoto, Hajime
author_sort Onoyama, Takumi
collection PubMed
description BACKGROUND: Programmed cell death-1 (PD-1) inhibitor has been indicated for many types of malignancies. However, these inhibitors also cause immune-related adverse events. Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%–4.5% of patients treated with PD-1 inhibitors. Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis (SC); however, the associated clinical and pathological features are unclear. AIM: To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature. METHODS: The review, conducted using electronic databases in PubMed, was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English. We scanned the references of the selected literature to identify any further relevant studies. Six cases previously studied by us, including three that have not yet been published, were included in this review. RESULTS: Thirty-one PD-1 inhibitor-related SC cases were evaluated. Median age of patients was 67 years (range, 43–89), with a male to female ratio of 21:10. The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer. Agents that caused PD-1 inhibitor-related SC were nivolumab (19 cases), pembrolizumab (10 cases), avelumab (1 case), and durvalumab (1 case). The median number of cycles until PD-1 inhibitor-related SC onset was 5.5 (range, 1–27). Abdominal pain or discomfort (35.5%, 11/31) was the most frequent symptom. Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes, and a normal level of serum immunoglobulin G4. Biliary dilation without obstruction (76.9%, 20/26), diffuse hypertrophy of the extrahepatic biliary tract (90.5%, 19/21), and multiple strictures of the intrahepatic biliary tract (30.4%, 7/23) were noted. In 11/23 (47.8%) cases, pathological examination indicated that CD8+ T cells were the dominant inflammatory cells in the bile duct or peribiliary tract. Although corticosteroids were mainly used for PD inhibitor-related SC treatment, the response rate was 11.5% (3/26). CONCLUSION: Some clinical and pathological features of PD-1 inhibitor-related SC were revealed. To establish diagnostic criteria for PD-1 inhibitor-related SC, more cases need to be evaluated.
format Online
Article
Text
id pubmed-6969883
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Baishideng Publishing Group Inc
record_format MEDLINE/PubMed
spelling pubmed-69698832020-01-28 Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review Onoyama, Takumi Takeda, Yohei Yamashita, Taro Hamamoto, Wataru Sakamoto, Yuri Koda, Hiroki Kawata, Soichiro Matsumoto, Kazuya Isomoto, Hajime World J Gastroenterol Systematic Reviews BACKGROUND: Programmed cell death-1 (PD-1) inhibitor has been indicated for many types of malignancies. However, these inhibitors also cause immune-related adverse events. Hepatobiliary disorder is a phenotype of immune-related adverse event affecting 0%–4.5% of patients treated with PD-1 inhibitors. Recent studies have reported PD-1 inhibitor-related sclerosing cholangitis (SC); however, the associated clinical and pathological features are unclear. AIM: To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature. METHODS: The review, conducted using electronic databases in PubMed, was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in English. We scanned the references of the selected literature to identify any further relevant studies. Six cases previously studied by us, including three that have not yet been published, were included in this review. RESULTS: Thirty-one PD-1 inhibitor-related SC cases were evaluated. Median age of patients was 67 years (range, 43–89), with a male to female ratio of 21:10. The main disease requiring PD-1 inhibitor treatment was non-small cell lung cancer. Agents that caused PD-1 inhibitor-related SC were nivolumab (19 cases), pembrolizumab (10 cases), avelumab (1 case), and durvalumab (1 case). The median number of cycles until PD-1 inhibitor-related SC onset was 5.5 (range, 1–27). Abdominal pain or discomfort (35.5%, 11/31) was the most frequent symptom. Blood serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes, and a normal level of serum immunoglobulin G4. Biliary dilation without obstruction (76.9%, 20/26), diffuse hypertrophy of the extrahepatic biliary tract (90.5%, 19/21), and multiple strictures of the intrahepatic biliary tract (30.4%, 7/23) were noted. In 11/23 (47.8%) cases, pathological examination indicated that CD8+ T cells were the dominant inflammatory cells in the bile duct or peribiliary tract. Although corticosteroids were mainly used for PD inhibitor-related SC treatment, the response rate was 11.5% (3/26). CONCLUSION: Some clinical and pathological features of PD-1 inhibitor-related SC were revealed. To establish diagnostic criteria for PD-1 inhibitor-related SC, more cases need to be evaluated. Baishideng Publishing Group Inc 2020-01-21 2020-01-21 /pmc/articles/PMC6969883/ /pubmed/31988594 http://dx.doi.org/10.3748/wjg.v26.i3.353 Text en ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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.
spellingShingle Systematic Reviews
Onoyama, Takumi
Takeda, Yohei
Yamashita, Taro
Hamamoto, Wataru
Sakamoto, Yuri
Koda, Hiroki
Kawata, Soichiro
Matsumoto, Kazuya
Isomoto, Hajime
Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review
title Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review
title_full Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review
title_fullStr Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review
title_full_unstemmed Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review
title_short Programmed cell death-1 inhibitor-related sclerosing cholangitis: A systematic review
title_sort programmed cell death-1 inhibitor-related sclerosing cholangitis: a systematic review
topic Systematic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969883/
https://www.ncbi.nlm.nih.gov/pubmed/31988594
http://dx.doi.org/10.3748/wjg.v26.i3.353
work_keys_str_mv AT onoyamatakumi programmedcelldeath1inhibitorrelatedsclerosingcholangitisasystematicreview
AT takedayohei programmedcelldeath1inhibitorrelatedsclerosingcholangitisasystematicreview
AT yamashitataro programmedcelldeath1inhibitorrelatedsclerosingcholangitisasystematicreview
AT hamamotowataru programmedcelldeath1inhibitorrelatedsclerosingcholangitisasystematicreview
AT sakamotoyuri programmedcelldeath1inhibitorrelatedsclerosingcholangitisasystematicreview
AT kodahiroki programmedcelldeath1inhibitorrelatedsclerosingcholangitisasystematicreview
AT kawatasoichiro programmedcelldeath1inhibitorrelatedsclerosingcholangitisasystematicreview
AT matsumotokazuya programmedcelldeath1inhibitorrelatedsclerosingcholangitisasystematicreview
AT isomotohajime programmedcelldeath1inhibitorrelatedsclerosingcholangitisasystematicreview