Can we prevent fatal liver failure under valproate

Valproic acid (VPA) has been used as an anticonvulsant for more than 30 years. Meanwhile, VPA has also been approved by the FDA for the treatment of bipolar disorders. We report the case of a 58-year-old female patient, who died from liver failure, probably due to treatment with VPA. The patient was admitted for bipolar affective disorder, currently depressed. Duloxetine was introduced as an antidepressant, VPA as a prophylactic treatment. 18 days after starting VPA treatment, the patient was admitted to a medical emergency unit due to diarrhea, gait ataxia and elevated temperature. Liver enzymes and creatinine were massively elevated. Due to acute hepatic failure, liver transplantation was performed. Histologically, extensive necrosis was demonstrated, with less than 5% of liver tissue preserved. The patient died of sepsis and multi-organ failure after five months. In this patient, liver failure occurred within less than three weeks after introduction of VPA and duloxetine. No other risk factors could be identified. The present case suggests that careful attention to clinical symptoms related to liver failure is of prime importance in VPA therapy to avoid a fatal outcome. A more intensive monitoring of liver enzymes as currently recommended after initiating VPA therapy might be considered.