Clinical Manifestations and Risk Factors of Liver Injury Induced by PD-1 Inhibitors in Patients with Malignancies: A Case-Control Study

Pengfei Zhao, Lihong Yu, Wenming Ma, Ting Zhao Department of Clinical Pharmacy, Weifang People’s Hospital, Shandong second Medical University, Weifang, Shandong Province, 261000, People’s Republic of ChinaCorrespondence: Ting Zhao, Department of Clinical Pharmacy, Weifang People’s Hospital, 151 Guangwen Street, Kuiwen District, Weifang, Shandong Province, 261000, People’s Republic of China, Tel +/Fax +860536-8192261, Email [email protected]: Hepatic injury induced by immune checkpoint inhibitors (ICPIs) is an inevitable challenge in the era of innovative anti-tumor therapies. However, studies on immune-related liver injury are relatively insufficient, and the associated risk factors are still lacking. The purpose of this study was to explore the incidence and clinical manifestations of immunotherapy-related liver injury.Methods: A retrospective case-control study was conducted involving patients treated with PD-1 inhibitors at Weifang People’s Hospital, a tertiary general hospital in China, from January 1, 2021 and July 31, 2024. Univariate and multivariate logistic regression analyses were employed to identify the potential risk factors. Then, the predictive value of these risk factors was evaluated using receiver operating characteristic (ROC) curve analysis.Results: In total, 300 patients were included. Among these patients, 52 patients experienced liver injury. The mean time from the initiation of immunotherapy to the onset of liver injury was 28.4 days, with a range from 2 to 219 days. 71.15% of patients developed liver injury within the first 30 days. 82.69% presented with mild cases (grade 1), 13.46% with moderate cases (grade 2), and 3.84% with severe cases (grades 3– 4). The overall incidence of PD-1 inhibitors-related liver injury was 0.34%. Specifically, nivolumab exhibited the highest incidence at 2.86%, followed by sintilimab at 0.41%. Both toripalimab and camrelizumab exhibited an incidence of 0.34%, while tislelizumab had the lowest at 0.28%. Multivariate logistic regression analysis showed that GGT and AST were independent risk factors for liver injury. ROC curve analysis revealed that patients with baseline ALT≥ 19.5 U/L, AST≥ 19.5 U/L, and GGT≥ 28.5 U/L were at increased risk of developing liver injury.Conclusion: In clinical therapy, close monitoring of liver function is recommended, especially for patients with baseline ALT≥ 19.5 U/L, AST≥ 19.5 U/L, and GGT≥ 28.5 U/L during immunotherapy with PD-1 inhibitors.Keywords: PD-1 inhibitors, immune-related adverse events, liver injury, incidence, risk factors