[Acute fatal liver insufficiency due to valproic acid therapy]

Fatal hepatic failure associated with valproic acid therapy is a rare side effect occurring in 1:5000-10,000 of the patients exposed to this antiepileptic drug. Its relevance arises from its fatal outcome and the high number of patients who are treated with this drug (one million worldwide in 1988). 112 cases were published up to 1988. Most of the affected patients were young (less than 10 years old), male, and mentally retarded. Many were under antiepileptic polytherapy. The children of this age group constituted only 23% of the patients treated with valproic acid but 73% of all fatalities. 90% of the patients developed hepatic failure in the first 5 months of therapy. Low doses or therapeutic serum levels of valproic acid do not prevent this dramatic event. Specific therapy is not known. In addition to the case report we review the literature and make recommendations for monitoring therapy with valproic acid.