Life sciences · Journal article
Frontiers in Oncology · October 7, 2026
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Background and aims Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) differs from chemotherapy- or targeted drug-related hepatotoxicity in pathogenesis and management. Biomarkers to distinguish ILICI from other anticancer agent-induced liver injuries are lacking. We compared the clinicopathological features, treatments, and outcomes of ILICI versus other anticancer agent-related liver injuries to identify distinguishing biomarkers. Methods We retrospectively included patients with liver injury during anticancer therapy at Fujian Cancer Hospital between June 2022 and November 2024. Cases were classified as ILICI or non-ILICI using the Common Terminology Criteria for Adverse Events v5.0 and the Roussel Uclaf Causality Assessment Method. Results Sixty-seven patients were enrolled, including 30 ILICI and 37 non-ILICI. ILICI was associated with more high-grade liver injury than non-ILICI ( P = 0.001), with similar latency, recovery time, and prognosis. Corticosteroids were administered in 70% of ILICI vs. 5.4% of non-ILICI patients ( P < 0.001). Among 29 liver biopsies (19 ILICI, 10 non-ILICI), ILICI showed a higher focal necrosis score ( P = 0.031) and programmed death-ligand 1 (PD-L1) expression in liver sinusoidal endothelial cells (LSECs), lymphocytes, and Kupffer cells (KCs) ( P = 0.007). Receiver operating characteristic analysis showed that a PD-L1 positivity cutoff of >30% in LSECs, lymphocytes, and KCs discriminated ILICI with an AUC of 0.811 (95%CI: 0.641–0.980). Sensitivity analyses and Firth penalized logistic regression confirmed that this finding remained robust after adjustment for confounders including pre-biopsy corticosteroid use and inactive HBV carrier status. Conclusions ILICI was associated with more severe hepatic inflammatory necrosis and a greater need for immunosuppressive therapy than non-ILICI. The PD-L1 positivity rate >30% in LSECs, lymphocytes, and KCs may serve as a potential diagnostic biomarker for ILICI.