König S A, Schenk M, Sick C, Holm E, Heubner C, Weiss A, König I, Hehlmann R
Children's Hospital, Mannheim, Germany.
Epilepsia. 1999 Jul;40(7):1036-40. doi: 10.1111/j.1528-1157.1999.tb00814.x.
Valproate (VPA)-associated hepatotoxicity is usually considered a problem of young children with polytherapy, mental retardation, and underlying metabolic defects.
An adult patient with fatal liver failure during treatment with VPA is presented, and a review of the literature on other adult patients is given.
A 29-year-old female patient with Friedreich's ataxia and partial seizures with acute liver failure during VPA treatment is reported. The first symptoms of liver failure (i.e., apathy during febrile upper airway infection) occurred 2 months after starting VPA therapy. VPA was discontinued 10 days later on hospital admission, when she had hepatic encephalopathy and severe bleeding diathesis. The patient died of severe liver failure and bronchopneumonia after 4 weeks of supportive treatment.
Twenty-six adult patients (>17 years) with VPA-associated fatal hepatotoxicity have been reported in the literature. Of the 26 adult patients, three were receiving VPA monotherapy. The age ranged between 17 and 62 years. The duration of VPA treatment before the first symptom varied between 7 days and 6 years. Twelve of the 26 affected adults had no underlying disease or a clearly nonmetabolic and non-hepatic disease. Therefore VPA-associated severe side effects also must be considered in adult patients without any evidence of a metabolic defect or underlying neurologic disease.
丙戊酸盐（VPA）相关的肝毒性通常被认为是患有多药治疗、智力发育迟缓及潜在代谢缺陷的幼儿所面临的问题。
本文介绍了一名在VPA治疗期间出现致命性肝衰竭的成年患者，并对其他成年患者的文献进行了综述。
报告了一名29岁患有弗里德赖希共济失调和部分性癫痫发作的女性患者，在VPA治疗期间出现急性肝衰竭。肝衰竭的首发症状（即发热性上呼吸道感染时出现淡漠）在开始VPA治疗2个月后出现。10天后因出现肝性脑病和严重出血倾向入院时停用了VPA。在支持治疗4周后，患者死于严重肝衰竭和支气管肺炎。
文献报道了26例（>17岁）与VPA相关的致命性肝毒性成年患者。在这26例成年患者中，3例接受VPA单药治疗。年龄范围在17至62岁之间。首次出现症状前VPA治疗的持续时间在7天至6年之间。26例受影响的成年人中有12例没有潜在疾病或明显的非代谢性和非肝脏疾病。因此，在没有任何代谢缺陷或潜在神经疾病证据的成年患者中，也必须考虑VPA相关的严重副作用。
