丙戊酸钠致严重急性肝损伤的回顾性分析

目的：探讨丙戊酸类药物致急性严重肝损伤的特点、相关因素及临床转归,为临床合理用药提供依据。方法：关键词以"丙戊酸"分别搭配"肝损害"肝损伤" "肝炎"肝毒性",检索CNKI期刊全文数据库和万方医学网相关文献,就药物不良反应（ADR）相关情况进行统计、分析。统计患者年龄、性别、日剂量、是否合并肝脏相关疾病、发生ADR时的用药时间、血药浓度、肝酶变化、临床表现与转归等情况。结果：共检索到丙戊酸类药物致严重肝损害的病例报告13篇,共15例。1）女性（占66.67%）患者占比较高;2）儿童（占40%）及老年人（占26.67%）是丙戊酸肝损伤的高危人群;3）丙戊酸初次用药后的前两个月是发生肝损伤的高危期;4）临床转归与肝损伤始发表现中的转氨酶水平高低无必然联系;5）肝脏相关疾病史不是丙戊酸钠导致急性肝损伤的影响因素,但肝脏疾病史与临床转归是否有必然联系尚有待临床进一步观察;6）肝损伤的发生与剂量过大、血药浓度过高无必然联系;7）多见皮肤/眼睑黄染、恶心/食欲不振等,也可见腹泻、水肿、发热、皮疹,偶见头晕头痛、皮肤红斑。结论：丙戊酸类药物可致急性肝损伤,严重时可致死。临床用药前应慎重选择用药人群,对患者既往肝脏疾病史、儿童、老人要慎重选用,使用过程中要密切监测肝功能;加强患者及家属用药教育,一旦发生疑似肝损伤症状,要及时就医,尽可能避免出现致死性结局。

Retrospective Analysis of Severe Acute Liver Injury Induced by Sodium Valproate

Objective: To discuss the characteristics, related factors and clinical outcomes of severe acute liver injury induced by sodium valproate so as to provide a basis for clinical rational drug use. Methods: The ages, sexes, daily dose, combination of liver related diseases, medication time of ADR, blood drug concentration, alteration of liver enzymes, clinical manifestations as well as prognosis were analyzed by searching CNKI and Wanfang databases with keywords of "sodium valproate" combined with "liver damage", "liver injury", "hepatitis", and "liver toxicity" respectively. Results: A total of 13 case reports including 15 cases of severe liver injury induced by sodium valproate were obtained. 1) Women (66.67%) accounted for a relatively high proportion of patients; 2) Children (40%) and the elderly (26.67%) were at high risk for liver injury; 3) The frst two months after the initial use of the drug was the high-risk period of liver injury; 4) There was no necessary association between the clinical outcome and the level of transaminase of the initial manifestations of liver injury; 5) The history of liver-related disease was not the influencing factor of acute liver injury caused by sodium valproate, but whether the clinical outcome and liver disease history were correlated or not had yet to be further clinically observed; 6) There was no necessary association between the live injury and the high dose as well as the high blood drug concentration; 7) Skin/eyelid yellow dye, nausea, loss of appetite, etc. were more common; diarrhea, edema, fever, rash, occasional dizziness headache, and skin erythema were also seen. Conclusion: Sodium valproate can cause acute liver injury and can be fatal. Patient population should be carefully selected before the clinical use of the drug. Patients with previous history of liver disease, children, and the elderly should carefully use the drug. The liver function should be closely monitored during the use of the drug. Education of patients and family members should be strengthened. Whenever suspected liver injury symptoms occur, patients should be given timely medical treatment as soon as possible to prevent the occurrence of fatal outcome.