Hepatotoxicity of valproic acid treatment

Hepatotoxicity of valproic acid (VPA) is reported in a psychomotor retarded boy. A four-month antiepileptic therapy was followed by a combined VPA/phenytoin treatment where-upon, two months later, the patient died in a hepatic coma. In the final state the metabolic pattern of VPA was still found within the normal range with the exception of the two abnormal metabolites 4-en-VPA) (2-propyl-4-pentenoic acid) and 4.4'-dien-VPA (2-(2-propenyl-4-pentenoic acid) detected only in low concentration. The amino acid pattern in plasma was characterized by a decrease or branched chain amino acids by 50% in contrast to the increase of the aromatic amino acids. Methionine, however, was in the normal range. Due to lack of a biochemical parameter indicating a possibly irreversible development of VPA induced hepatotoxicity stopping of VPA therapy should be obligatory if abnormal unsaturated VPA metabolites are detected or if dien-VPA/3, a normal metabolic compound, is increased above the normal range. L-carnitine treatment is recommended as a prophylactic therapy.