Immune-related cholangitis induced by immune checkpoint inhibitors: a systematic review of clinical features and management

Background aims: Immune checkpoint inhibitors (ICIs) improve the survival of patients with advanced tumors. However, immune-related adverse events limit the use of ICIs. Although liver toxicity has been concerned gradually, little is known about bile duct injury associated with ICIs. Hence, this review aims to describe clinicopathological features, imaging, and management of immune-mediated cholangitis (IMC) induced by ICIs.

Methods: We retrieved the literature from the PubMed database for case reports and series of IMC induced by ICIs. IMC was then classified as small-ducts type, large-ducts type and mixed type. Biochemical parameters, pathological characteristics, imaging features, treatment and response were evaluated and compared among three patterns.

Results: Fifty-three cases of IMC were enrolled. The median values of alkaline phosphatase and alanine transaminase of IMC were 1328 and 156 IU/L. The ALP level of the large-ducts type was higher than that of the small-ducts type (P = 0.021). The main pathological characteristics of small-ducts cholangitis were portal inflammation, bile duct injury and ductular reaction. The imaging features of large-duct cholangitis were bile duct dilatation, stenosis and bile duct wall thickening and irregularity. Forty-eight (90%) cases received immunosuppression therapy. Biliary enzymes reduced in 79% of cases receiving immunosuppression therapy, but only 8.5% of cases returned to normal. It took a long time for biliary enzymes to recover.

Conclusions: The clinicians should be aware of the possibility of IMC if the biliary enzymes increase significantly after the use of ICIs. The liver function can be improved partially by immunosuppressive therapy in the majority of IMC.