A retrospective analysis of liver dysfunction and its risk factors in lung cancer patients receiving PD-1/PD-L1 inhibitor therapy

Primary lung cancer remains one of the most common and lethal malignancies worldwide, with especially high incidence and mortality in China. Although advancements in targeted therapies and immunotherapy have significantly improved patient outcomes, immune-related adverse events-notably hepatotoxicity-pose increasing clinical challenges. This retrospective study investigated the frequency and contributing factors of liver dysfunction in patients with primary lung cancer undergoing programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy in a resource-constrained setting. Medical records of 82 individuals treated with PD-1/PD-L1 inhibitors at our institution between June 2022 and June 2024 were analyzed. Hepatic impairment was defined based on the National Cancer Institute's Common Terminology Criteria for Adverse Events. Liver dysfunction was observed in 16 patients (19.51%). Multivariate logistic regression identified 5 independent predictors of liver impairment: age > 60 years (odds ratio [OR] = 3.802; 95% CI: 1.217-11.888; P = .021), alcohol use (OR = 2.709; 95% CI: 1.063-6.879; P = .037), ECOG performance status of 2 (OR = 2.865; 95% CI: 1.044-7.885; P = .041), PD-1 inhibitor administration (OR = 3.916; 95% CI: 1.228-12.426; P = .021), and combination treatment regimens (OR = 3.409; 95% CI: 1.169-9.930; P = .025). These findings highlight that approximately one-fifth of patients experienced hepatic toxicity during immune checkpoint blockade, with advanced age, alcohol intake, reduced functional status, PD-1 agent use, and multidrug protocols significantly elevating risk. Enhanced vigilance and personalized treatment strategies are essential to minimize toxicity and ensure safer immunotherapy delivery in vulnerable populations.