Characteristics of Immune Checkpoint Inhibitor (ICI)-Related Hepatotoxicity Based on the Baseline Liver Function.

Purpose: This study estimated the incidence of immune checkpoint inhibitor-related hepatotoxicity (ICH), identified risk factors, and characterized patients who developed ICH.

Materials and methods: Adult patients treated with ICIs from January 2015 to June 2022 in a tertiary hospital were included, excluding those without liver function tests or those with liver cancer but normal baseline liver function. Patients were stratified by baseline liver function status; in overall and each of stratified cohorts ICH incidence was calculated as the number of events per 100 person-years with grade 3 hepatotoxicity as the primary outcome. Patient characteristics were assessed using descriptive statistics, and risk factors were identified through multivariable Cox regression. Causality between ICI use and hepatotoxicity was assessed using the Naranjo Algorithm.

Results: Among 803 patients, the ICH incidence was 19.5 cases per 100 person-years, with a higher incidence (47.3 vs. 9.3 cases per 100 person-years) and earlier onset (13 vs. 15 days) in the abnormal compared to the normal group. Significant risk factors for ICH included female sex in the normal group and liver cancer in the abnormal group. According to the Naranjo Algorithm, all the 60 ICH cases were classified as "probable" or "possible". Among the 60 cases, 62% (n=37) resulted in ICI discontinuation. The baseline liver function did not impact on the severity or the likelihood of ICI discontinuation.

Conclusion: Future studies are needed to evaluate whether the impact of ICI discontinuation on survival outcomes in patients with ICH varies based on baseline liver function abnormalities.