Fatal liver failure associated with valproate therapy in a patient with Friedreich's disease: Review of valproate hepatotoxicity in adults

Purpose: Valproate (VPA)-associated hepatotoxicity is usually considered a problem of young children with polytherapy, mental retardation, and underly ing metabolic defects. Methods: An adult patient with fatal liver failure during treatment with VP A is presented, and a review of the literature on other adult patients is g iven. Results: A 29-year-old female patient with Friedreich's ataxia and partial seizures with acute liver failure during VPA treatment is reported. The fir st symptoms of liver failure (i.e., apathy during febrile upper airway infe ction) occurred 2 months after starting VPA therapy. VPA was discontinued 1 0 days later on hospital admission, when she had hepatic encephalopathy and severe bleeding diathesis. The patient died of severe liver failure and br onchopneumonia after 4 weeks of supportive treatment. Conclusions: Twenty-six adult patients (>17 years) with VPA-associated fata l hepatotoxicity have been reported in the literature. Of the 26 adult pati ents, three were receiving VPA monotherapy. The age ranged between 17 and 6 2 years. The duration of VPA treatment before the first symptom varied betw een 7 days and 6 years. Twelve of the 26 affected adults had no underlying disease or a clearly nonmetabolic and nonhepatic disease. Therefore VPA-ass ociated severe side effects also must be considered in adult patients witho ut any evidence of a metabolic defect or underlying neurologic disease.