Chen Yue, Wang Yadong, Xia Runan, Chen Yi, Xie Xuefeng
School of Pharmacy, Anhui Medical University, Hefei, China; Department of Pharmacy, Lu'an People's Hospital, Lu'an, China.
School of Pharmacy, Anhui Medical University, Hefei, China; Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, China.
Biomol Biomed. 2025 Apr 26;25(6):1335-1344. doi: 10.17305/bb.2024.11258.
The risk factors for liver injury induced by valproic acid (VPA) are not well understood, and no predictive tool currently exists to identify patients at risk. This study aims to explore these risk factors and develop a predictive model. We collected medical data from patients treated with VPA between January 1, 2020, and October 31, 2023. Prescription sequence analysis was used to identify patients with suspected VPA-induced liver injury, and the Roussel Uclaf Causality Assessment Method was applied to confirm the diagnosis. Risk factors were analyzed using logistic regression, and a nomogram model was developed and evaluated. A total of 256 cases were included in the study: 64 in the VPA-induced liver injury group and 192 in the control group. The incidence of liver injury was 5.3%. Multivariate logistic regression analysis revealed that dysglycemia (odds ratio [OR] = 5.171; 95% confidence interval [CI]: 1.254-21.325), hyperlipidemia (OR = 4.903; 95% CI: 1.400-17.173), surgery (OR = 10.020; 95% CI: 1.737-57.805), and hypokalemia (OR = 10.407; 95% CI: 2.398-45.173) were significant independent risk factors for VPA-induced liver injury. The area under the receiver operating characteristic curve was 0.904 (95% CI: 0.860-0.947), indicating excellent model performance. The Hosmer-Lemeshow test yielded a P value of 0.2671, and the calibration plot slope was close to one, further supporting the model's accuracy. The findings suggest that patients with dysglycemia, hyperlipidemia, a history of surgery, and hypokalemia are at higher risk for VPA-induced liver injury. The nomogram model provides a reliable method for predicting the likelihood of liver injury in these patients.
丙戊酸（VPA）所致肝损伤的危险因素尚不清楚，目前也没有预测工具来识别有风险的患者。本研究旨在探讨这些危险因素并建立预测模型。我们收集了2020年1月1日至2023年10月31日期间接受VPA治疗患者的医疗数据。采用处方序列分析来识别疑似VPA所致肝损伤的患者，并应用鲁塞尔乌克拉夫因果关系评估法来确诊。使用逻辑回归分析危险因素，并建立和评估列线图模型。本研究共纳入256例病例：VPA所致肝损伤组64例，对照组192例。肝损伤发生率为5.3%。多因素逻辑回归分析显示，血糖异常（比值比[OR]=5.171；95%置信区间[CI]：1.254 - 21.325）、高脂血症（OR = 4.903；95% CI：1.400 - 17.173）手术（OR = 10.020；95% CI：1.737 - 57.805）和低钾血症（OR = 10.407；95% CI：2.398 - 45.173）是VPA所致肝损伤的显著独立危险因素。受试者工作特征曲线下面积为0.904（95% CI：0.860 - 0.947），表明模型性能良好。Hosmer-Lemeshow检验的P值为0.2671，校准图斜率接近1，进一步支持了模型的准确性。研究结果表明，血糖异常、高脂血症、有手术史和低钾血症的患者发生VPA所致肝损伤的风险更高。列线图模型为预测这些患者肝损伤的可能性提供了一种可靠的方法。
