Abdominal pain accompanied by elevated serum inflammatory markers and biliary enzymes for diagnosing immune checkpoint inhibitor-induced sclerosing cholangitis

Immune-related sclerosing cholangitis (irSC) is relatively rare and its clinical characteristics are not well known. In this study, we aimed to summarize the clinical features of irSC. Clinical data were collected retrospectively from 1,393 patients with advanced malignancy treated with immune-checkpoint inhibitors (ICIs) between August 2014 and October 2021. We analyzed patients with immune-related adverse events of liver injury (liver-irAEs) and compared irSC and non-irSC groups. Sixty-seven patients (4.8%) had a liver-irAE (>= grade 3) during the follow-up period (median, 262 days). Among these, irSC was observed in eight patients (11.9%). All patients in the irSC group were treated with anti-PD-1/PD-L1 antibodies. Compared with the non-irSC group, the irSC group showed mainly non-hepatocellular liver injury (87.5 % vs 50.8 %, P = 0.065), and had elevated serum inflammatory markers (e.g., CRP and NLR) and biliary enzymes (e.g., GGTP and ALP) at the onset of liver-irAEs. Furthermore, most patients with irSC had abdominal pain. In the non-irSC group, the liver injury of 23 patients improved only with the discontinuation of ICIs, and 22 patients improved with medication including prednisolone (PSL). Conversely, almost all patients (n=7) in the irSC group were treated with PSL, but only two patients experienced an improvement in liver injury. We found that irSC is characterized by a non-hepatocellular type of liver injury with abdominal pain and a high inflammatory response and is refractory to treatment. Further examination by imaging is recommended to detect intractable irSC in cases with these characteristics.

Automated summary

Immune-related sclerosing cholangitis (irSC) is a rare disease with unclear clinical characteristics. This study aimed to summarize the clinical features of irSC. Retrospective analysis of clinical data from 1,393 advanced malignancy patients treated with immune-checkpoint inhibitors revealed that eight patients (11.9%) developed irSC as an immune-related adverse event. Compared to the non-irSC group, patients with irSC had a non-hepatocellular liver injury, elevated inflammatory markers, and biliary enzymes at the onset of liver injury. Additionally, abdominal pain was a common symptom in irSC patients. Treatment for irSC was found to be refractory, with only two patients experiencing improvement in liver injury. Further imaging examination is recommended for detecting intractable irSC in cases with these characteristics.