FATAL LIVER-FAILURE IN 16 CHILDREN WITH VALPROATE THERAPY

被引:132
作者
SCHEFFNER, D
KONIG, S
RAUTERBERGRULAND, I
KOCHEN, W
HOFMANN, WJ
UNKELBACH, S
机构
[1] UNIV HEIDELBERG, INST PATHOL, D-6900 HEIDELBERG, FED REP GER
[2] UNIV HOMBURG, CHILDRENS HOSP, D-6650 HOMBURG, FED REP GER
关键词
D O I
10.1111/j.1528-1157.1988.tb03757.x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The data of 16 children who died while receiving valproate (VPA) therapy in West Germany were analyzed. Five were normally developed, 5 were receiving VPA-monotherapy, and only 2 patients were aged <3 years. The first clinical symptoms of impending hepatotoxicity usually included nausea, vomiting, and apathy; pathologic laboratory tests reflected liver failure. Liver histology revealed microvesicular steatosis, cell necrosis, and bile duct proliferation of varying degree. An abnormal metabolite, 4-ene-VPA, was detected in all examined patients (six of six) and persisted after drug withdrawal. The pathogenesis of fatal liver failure during VPA treatment remains unknown. World-wide, .apprx.100 fatalities have been reported in relation to VPA treatment. More than 90% were aged <20 years, 95% developed their first symptoms within the first 6 months of treatment, and 16 were treated with VPA alone. Since it is difficult precisely to define a group at risk for fatalities with VPA, careful clinical and laboratory monitoring with a special focus on vomiting and apathy, liver enzymes, and coagulation tests seem mandatory during the first 6 months after introduction of VPA. Taking into account the considerable number of fatalities during VPA treatment, the indication for its use requires careful reevaluation.
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收藏
页码:530 / 542
页数:13
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