Real world data of liver injury induced by immune checkpoint inhibitors in Japanese patients with advanced malignancies

Background Liver injury induced by immune checkpoint inhibitors (ICIs) is an immune-related adverse event (irAE) whose incidence has increased with the broader use of ICIs in clinical practice. However, the incidental risk factors of immune-related liver injury are unknown. We investigated the clinical characteristics of immune-related liver injury. Methods A total of 546 patients treated with ICIs for advanced malignancies between September 2014 and February 2019 were included retrospectively. Factors associated with immune-related liver injury were determined. Results Immune-related liver injury (>= Grade 3) occurred in 29 (5.3%) patients (Grade 3, n = 20; Grade 4, n = 8; Grade 5, n = 1) during the follow-up period (median 153 days). The patterns of liver injuries were hepatocellular, n = 6 (20.7%); cholestatic, n = 17 (58.6%); and mixed, n = 6 (20.7%). The median period between the initial administration of ICIs and the incidence of irAEs was 52 days. Of 29 patients with immune-related liver injury (>= Grade 3), four showed immune-related cholangitis with non-obstructive dilation of the bile ducts. Factors that were significantly associated with the incidence of immune-related liver injury in multivariate analysis were use of ipilimumab, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent [hazard ratio [HR] 4.22, 95% confidence interval (CI) 1.65-10.80, P = 0.003], and fever over 38 degrees C within 24 h of initial ICI administration (HR 6.21, 95% CI 2.68-14.40, P < 0.001). Conclusions We found that the use of ipilimumab and the presence of fever within 24 h of initial ICI administration were predictive factors for immune-related liver injury.