Clinicopathologic characteristics and diagnostic value of PD-L1 in immune checkpoint inhibitor-related liver injury: a single-center retrospective study

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: = 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.