Clinical features and pathological findings by liver biopsy in patients with immune-related sclerosing cholangitis induced by immune checkpoint inhibitors

Abstract

Background: Immune-related sclerosing cholangitis (irSC) induced by immune checkpoint inhibitors (ICIs) is relatively rare, and its clinical and pathological features are not well known.

Aims: We aimed to compare the clinical course and pathological findings of irSC with those of non-irSC liver injury.

Methods: Clinical data were retrospectively collected from 2416 patients with advanced malignancies treated with ICIs between September 2014 and October 2023. The data of patients with severe ICI-induced liver injury who underwent liver biopsy were analyzed and compared between patients with irSC and non-irSC.

Results: Ninety-three (3.8 %) patients had severe ICI-induced liver injury, and 38 underwent liver biopsy. Of these, five were diagnosed with irSC. The irSC group had a significantly longer time to onset of ICI-induced liver injury and a lower rate of improvement of liver injury than did the non-irSC group (irSC, 3/5; non-irSC, 32/33). Liver biopsies revealed more moderate-to-severe pathological cholangitis in the irSC group than in the non-irSC group (irSC, n = 5/5; non-irSC, n = 16/33). Other pathological findings were similar between the two groups.

Conclusion: Appropriate management of irSC requires an understanding of its characteristics of late onset and steroid resistance, and liver biopsy, in addition to imaging, may be useful for diagnosing irSC.

Keywords: Drug-induced liver injury; Immune checkpoint inhibitor; Immune-related adverse events.