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… Click to show full abstract
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 °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.
               
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