Evaluation of immune checkpoint inhibitor-associated hepatotoxic adverse events: A pharmacovigilance analysis based on the FAERS database

Objective: To investigate the comprehensive landscape of hepatotoxic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs), with a special focus on evaluating the potential risk of lethal hepatotoxic AEs. Introduction: The widespread adoption of ICIs has markedly improved the prognosis for patients with advanced cancer. However, this therapeutic advance is accompanied by the risk of immune-related adverse events (irAEs), especially hepatotoxic AEs, which particularly affect patients with pre-existing liver diseases or hepatobiliary cancers. Methods: Reports in the FAERS database from Q1 2014 to Q3 2024 were collected. The characteristics of ICI-related hepatotoxic AEs were summarized. Disproportionality analysis was conducted to calculate reported odds ratios for assessing signals of hepatotoxic AEs. Additionally, logistic regression was employed to evaluate patient-related factors contributing to an increased risk of these AEs. Results: Hepatotoxic AEs increased yearly and occurred primarily in patients with hepatobiliary tumors. CTLA-4 inhibitors exhibited the highest incidence of AEs. In contrast, PD-1 inhibitors had the shortest median time to AE onset. Abnormal hepatic function was a common AE, whereas Stauffer’s syndrome was identified as a rare AE. The risk of hepatotoxic AEs was notably elevated by combination immunotherapy and the concurrent use of specific drugs. Despite variations in the safety profiles of different ICI regimens, these differences did not significantly influence the risk of fatal hepatotoxicity. Furthermore, older men who experienced other AEs were found to be at higher risk for developing fatal hepatotoxicity. Conclusion: The safety profiles of different ICIs vary widely, necessitating individualized drug selection based on patient-specific factors.