Liver test pattern and histologic bile duct injury do not predict response to treatment of immunotherapy hepatotoxicity.

[BACKGROUND AND AIMS] Immune checkpoint inhibitor (ICI) cholangitis is an uncommon immune-related adverse event affecting the biliary ducts that is considered distinct from ICI hepatitis. This study examines whether the liver injury pattern or presence of histologic bile duct damage determines response to immunosuppression.

[METHODS] This multicenter retrospective cohort study includes 298 consecutive patients with cancer who received immunotherapy between 2010 and 2021 and were originally classified as grade 3 or higher ICI-related hepatitis [alanine aminotransferase (ALT) ≥ 200 U/L]. Response to immunosuppression was stratified by pattern of liver injury (hepatocellular, cholestatic, or mixed) as defined by R-value, the presence of histologic bile duct damage, and the Drug-Induced Liver Injury Network (DILIN) severity score. The primary outcome was time to normalization of ALT (≤40 U/L). Secondary outcomes included time to grade 1 liver injury (ALT ≤ 100 U/L), need for additional immunosuppression, hospitalization, and death.

[RESULTS] The pattern of liver injury was hepatocellular in 60%, cholestatic in 13%, and mixed in 27%. All patients received corticosteroids as first-line therapy. There was no difference in corticosteroid dose, need for an additional immunosuppressive agent, time to normalization of ALT, or time to grade 1 liver injury between groups. Outcomes were similar among patients with or without histologic bile duct damage and between those with a DILIN severity score of 3+ versus a lower score.

[CONCLUSIONS] The response of high-grade ICI hepatotoxicity to standard immunosuppression is similar regardless of the pattern of liver injury or the presence of bile duct damage.