Zheng Caiyun, Huang Shunmin, Lin Meimei, Hong Baohui, Dai Hengfen, Yang Jing
Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Fuqing City Hospital Affiliated to Fujian Medical University, Fuzhou, Fujian, China.
J Clin Transl Hepatol. 2023 Nov 28;11(6):1387-1396. doi: 10.14218/JCTH.2023.00124. Epub 2023 Jul 7.
Immune-mediated liver injury is a fatal side effect of sintilimab. This study aimed to shed light on the associated risk factors and characteristics of this adverse event.
The clinical records of 772 patients treated with sintilimab were retrospectively reviewed to investigate risk factors associated with sintilimab immune-related hepatotoxicity, as well as its incidence and outcome. The Roussel Uclaf Causality Assessment Method was used to identify cases of sintilimab-induced hepatotoxicity. Furthermore, logistic regressions were performed to compare the clinical and bloodwork characteristics of patients with and without immune-mediated liver injury caused by checkpoint inhibitors.
Of the 585 patients included in the study, 71 (12.1%) developed liver injury during sintilimab use. The median RUCAM score with interquartile range was 7 (6, 8). Hypoproteinemia, dyslipidemia, and the presence of thyroid peroxidase antibodies were risk factors for sintilimab-related hepatotoxicity. A nomogram model was constructed for sintilimab-induced immune-mediated liver injury based on these risk factors, which had a C-index value of 0.713 and a good calibration curve. When applied to patients with grade ≥3 and ≥4 sintilimab-induced immune-mediated liver injury, it achieved C-index values of 0.752 and 0.811, respectively. The nomogram model also showed a good prediction potential in patients ≥65 years and males. Six of the patients with sintilimab-related hepatotoxicity showed improved liver function upon treatment with steroids.
This study demonstrated that hypoproteinemia, dyslipidemia, and the presence of thyroid peroxidase antibodies were clinically feasible prognostic biomarkers to predict liver injury in patients treated with sintilimab.
免疫介导的肝损伤是信迪利单抗的一种致命副作用。本研究旨在阐明这一不良事件的相关危险因素及特征。
回顾性分析772例接受信迪利单抗治疗患者的临床记录，以调查与信迪利单抗免疫相关肝毒性相关的危险因素及其发生率和转归。采用乌氏因果关系评估法确定信迪利单抗所致肝毒性病例。此外，进行逻辑回归以比较有和没有由检查点抑制剂引起的免疫介导肝损伤患者的临床和血液学特征。
在纳入研究的585例患者中，71例（12.1%）在使用信迪利单抗期间发生肝损伤。RUCAM评分中位数及四分位数间距为7（6，8）。低蛋白血症、血脂异常和甲状腺过氧化物酶抗体的存在是信迪利单抗相关肝毒性的危险因素。基于这些危险因素构建了信迪利单抗诱导的免疫介导肝损伤的列线图模型，其C指数值为0.713，校准曲线良好。当应用于信迪利单抗诱导的3级及以上和4级免疫介导肝损伤患者时，其C指数值分别为0.
