Central Laboratory, the First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, 150001, Heilongjiang, China.
Department of Hematology, Southern University of Science and Technology Hospital, Shenzhen, China.
Biol Trace Elem Res. 2024 Jan;202(1):122-132. doi: 10.1007/s12011-023-03676-2. Epub 2023 Apr 25.
Arsenic trioxide (ATO)-induced hepatotoxicity is often observed in acute promyelocytic leukemia (APL) patients and decreases therapeutic effect of ATO. Thus, concerns over hepatotoxicity have been raised. The aim of this study was to explore some noninvasive clinical indicators that can be used to guide the individualized application of ATO in the future. APL patients treated with ATO were identified retrospectively via electronic health records at our hospital from August 2014 through August 2019. APL patients without hepatotoxicity were selected as controls. The association between putative risk factors and ATO-induced hepatotoxicity was estimated with ORs and 95% CIs, which were calculated using the chi-square test. The subsequent multivariate analysis was performed using logistic regression analysis. In total, 58.04% of patients experienced ATO-induced hepatotoxicity during the first week. Elevated hemoglobin (OR 8.653, 95% CI, 1.339-55.921), administration of nonprophylactic hepatoprotective agents (OR 36.455, 95% CI, 7.409-179.364), non-single-agent ATO to combat leukocytosis (OR 20.108, 95% CI, 1.357-297.893) and decreased fibrinogen (OR 3.496, 95% CI, 1.127-10.846) were found to be statistically significant risk factors for ATO-induced hepatotoxicity. The area under the ROC curve values were 0.846 for "overall ATO-induced hepatotoxicity" and 0.819 for "early ATO-induced hepatotoxicity." The results revealed that hemoglobin ≥ 80 g/L, nonprophylactic hepatoprotective agents, and non-single-agent ATO and fibrinogen < 1 g/L are risk factors for ATO-induced hepatotoxicity in newly diagnosed APL patients. These findings can enhance the clinical diagnosis of hepatotoxicity. Prospective studies should be performed in the future to validate these findings.
三氧化二砷（ATO）诱导的肝毒性在急性早幼粒细胞白血病（APL）患者中经常观察到，并降低 ATO 的治疗效果。因此，人们对肝毒性表示关注。本研究旨在探索一些可用于指导未来 ATO 个体化应用的非侵入性临床指标。通过我院电子病历回顾性识别 2014 年 8 月至 2019 年 8 月期间接受 ATO 治疗的 APL 患者，选择无肝毒性的 APL 患者作为对照。使用 OR 和 95%CI 估计潜在危险因素与 ATO 诱导的肝毒性之间的关系，使用卡方检验进行计算。随后的多变量分析使用逻辑回归分析进行。在第一周内，58.04%的患者发生 ATO 诱导的肝毒性。血红蛋白升高（OR 8.653，95%CI，1.339-55.921）、使用非预防性肝保护剂（OR 36.455，95%CI，7.409-179.364）、非单一 ATO 治疗白细胞增多（OR 20.108，95%CI，1.357-297.893）和纤维蛋白原降低（OR 3.496，95%CI，1.127-10.846）被发现是 ATO 诱导的肝毒性的统计学显著危险因素。ROC 曲线下面积分别为 0.846（“总 ATO 诱导的肝毒性”）和 0.819（“早期 ATO 诱导的肝毒性”）。结果表明，血红蛋白≥80g/L、非预防性肝保护剂、非单一 ATO 和纤维蛋白原<1g/L 是新诊断的 APL 患者 ATO 诱导的肝毒性的危险因素。这些发现可以增强肝毒性的临床诊断。未来应进行前瞻性研究来验证这些发现。
