Impact of different subtypes of steatotic liver disease on immune checkpoint inhibitor-related drug-induced liver injury: a retrospective study.

[OBJECTIVE] Programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) inhibitors are increasingly implicated in cases of drug-induced liver injury (DILI). While previous studies have established a correlation between chronic liver diseases and DILI, investigations into the association between steatotic liver disease (SLD) and DILI remain limited. This study aimed to evaluate the clinical characteristics and risk factors associated with PD-(L)1 inhibitor-related DILI, with particular emphasis on the impact of SLD on DILI incidence.

[METHODS] Clinical data from patients with extrahepatic malignancies who received PD-(L)1 inhibitors between January 2020 and December 2024 were retrospectively analysed. Causality between liver injury events and PD-(L)1 inhibitors was assessed using the updated Roussel Uclaf Causality Assessment Method.

[RESULTS] Among the 958 patients treated with PD-(L)1 inhibitors, 62 (6.5%) developed PD-(L)1 inhibitor-related DILI. A total of 364 (38.0%) had SLD, of whom 310 (32.4%) were classified as metabolic dysfunction-associated steatotic liver disease (MASLD), 18 (1.9%) as MASLD with increased alcohol consumption, and 36 (3.8%) as MASLD with chronic hepatitis virus infection. Multivariate analysis demonstrated that patients with SLD had a 5.6-fold increased risk of developing DILI (95% confidence interval: 3.42-9.12, P  < 0.001); however, no association was observed between MASLD and an increased DILI risk. Notably, DILI risk was significantly higher in patients with steatosis combined with chronic hepatitis virus infection or heavy alcohol consumption.

[CONCLUSION] Hepatic steatosis is associated with an increased risk of PD-(L)1 inhibitor-related liver injury in patients with extrahepatic malignancies, particularly in the presence of multiple underlying aetiologies.