Department of Pharmacy, Shanxi Provincial People's Hospital, Taiyuan, China.
Department of Neurosurgery, Shanxi Provincial People's Hospital, Taiyuan, China.
Ann Pharmacother. 2022 Aug;56(8):888-897. doi: 10.1177/10600280211055508. Epub 2021 Nov 8.
Valproic acid (VPA) has been widely used to prevent epileptic seizures after neurosurgery in China. We have found that the incidence of liver injury (LI) in patients using VPA after neurosurgery is higher than that in other patients.
The objective of this study was to investigate the risk factors of LI in patients using VPA after neurosurgery.
A nested case-control study was conducted in patients using VPA after neurosurgery between September 2019 and March 2021. Cases of LI were matched to controls by age and body mass index (BMI). Conditional logistic regression was used to estimate matched odds ratios representing the odds of LI. A receiver operating characteristic curve was used to analyze the optimal cutoff condition.
A total of 248 people (62 LI and 186 control) were enrolled. Among patients with vs without LI, the matched odds ratio for trough concentration of VPA was significant (matched odds ratio [OR], 1.09; 95% confidence interval [CI]: 1.01-1.19). The course of treatment (OR: 1.17, 95% CI: 1.02-1.33), Glasgow score (OR: 0.26, 95% CI: 0.10-0.67), gene polymorphisms of CYP2C19 (OR: 2.09, 95% CI: 1.03-146.93), and UGT1A6 (OR: 34.61, 95% CI: 1.19-1003.23) were all related to the outcome. The optimal cutoff of the course of treatment was 10 days, while the trough concentration of VPA was determined to be 66.16 mg/L.
Length of treatment, VPA trough concentration, and Glasgow score were associated with LI in patients after neurosurgery. A gene test may be necessary for people who are prescribed VPA for a long time.
在中国，丙戊酸（VPA）已广泛用于神经外科手术后预防癫痫发作。我们发现，神经外科手术后使用 VPA 的患者发生肝损伤（LI）的发生率高于其他患者。
本研究旨在探讨神经外科手术后使用 VPA 的患者发生 LI 的危险因素。
本研究采用巢式病例对照研究，纳入 2019 年 9 月至 2021 年 3 月期间神经外科手术后使用 VPA 的患者。将 LI 病例与年龄和体重指数（BMI）相匹配的对照进行匹配。采用条件 logistic 回归估计代表 LI 发生概率的匹配比值比。采用受试者工作特征曲线分析最佳截断条件。
共纳入 248 人（62 例 LI 和 186 例对照）。与无 LI 患者相比，VPA 谷浓度的匹配比值比有统计学意义（匹配比值比[OR]，1.09；95%置信区间[CI]：1.01-1.19）。疗程（OR：1.17，95%CI：1.02-1.33）、格拉斯哥评分（OR：0.26，95%CI：0.10-0.67）、CYP2C19 基因多态性（OR：2.09，95%CI：1.03-146.93）和 UGT1A6（OR：34.61，95%CI：1.19-1003.23）均与结局相关。疗程的最佳截断值为 10 天，VPA 谷浓度为 66.16mg/L。
神经外科手术后患者的治疗时间、VPA 谷浓度和格拉斯哥评分与 LI 相关。对于长期服用 VPA 的患者，可能需要进行基因检测。
