Published online Jan 21, 2020. doi: 10.3748/wjg.v26.i3.353
Peer-review started: November 23, 2019
First decision: December 23, 2019
Revised: January 7, 2020
Accepted: January 11, 2020
Article in press: January 11, 2020
Published online: January 21, 2020
Programmed cell death-1 (PD-1) inhibitor has been indicated for many types of malignancies. On the other hands, these inhibitors cause immune-related adverse events (irAEs). Hepatobiliary disorder is a phenotype of irAEs that affect 0%–4.5% of patients treated with PD-1 inhibitors.
Recently, PD-1 inhibitor-related sclerosing cholangitis (SC), one of the irAEs, have been reported. However, the clinical and pathological features of PD-1 inhibitor-related SC are uncertain.
The objective of this study to evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the literature.
We conducted an electronic search through databases of PubMed. The review 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. The reference lists of the identified papers were also scanned to find out further relevant studies. Six cases previously studied by us, including three that have not yet been published, were included in this review.
Thirty-one PD-1 inhibitor-related SC cases were evaluated. 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. Liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes, and a normal level of serum IgG4 were shown in blood serum test. 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. CD8+ T cells were the dominant inflammatory cells in the bile duct or peribiliary tract in 11/23 (47.8%) cases. The response rate of corticosteroids for PD inhibitor-related SC was 11.5% (3/26).
Some clinical features of PD-1 inhibitor-related SC, such as biliary dilation without obstruction, diffuse hypertrophy of the extrahepatic biliary tract and/or multiple strictures of intrahepatic biliary tract, liver dysfunction with a dominant increase in biliary tract enzymes relative to hepatic enzymes, normal level of serum IgG4, and a moderate-to-poor response to steroid therapy, were revealed.
To establish the diagnostic criteria for PD-1 inhibitor-related SC, more cases, for which clinical data including hepatobiliary enzymes, immunological marker, image findings, and pathological evaluation were presented clearly, need to be evaluated. We will have to find more specific features of PD-1 inhibitor-related SC.