Frontiers in oncology · 2026
Clinicopathologic characteristics and diagnostic value of PD-L1 in immune checkpoint inhibitor-related liver injury: a single-center retrospective study.
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Lai Huaying, Zhao Xinyan, Zhou Dongmei, Lin Luping, Zhang Jianwei, Chen Yu, Huang Sha
Аннотация
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.
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.