Idiosyncratic Valproic Acid-Induced Hepatotoxicity in a Sickle Cell Patient

Objective: Suspected idiosyncratic valproic acid-induced hepatotoxicity in a sickle cell patient with chronic migraines is reported. Case Summary: A 32-year-old female with a medical history significant for sickle cell anemia and cerebral palsy was admitted to an inpatient medicine service for moderate to severe right flank pain with worsening transaminitis and hyperbilirubinemia. The patient reported taking valproic acid for approximately 6 years for the prevention of chronic migraines. An extensive workup was inconclusive for an etiology of underlying liver disease for the presenting symptoms. Valproic acid was discontinued on hospitalization day 3, resulting in a rapid improvement of the signs and symptoms of hepatotoxicity. Discussion: Several mechanisms of idiopathic valproic acid-induced hepatotoxicity have been proposed, including the accumulation of hepatotoxic metabolites, induction of oxidative stress, and deficiency of l-carnitine. Drug-induced hepatotoxicity is typically confirmed following improvement on withdrawal of the suspected agent and exclusion of any underlying etiologies. For this particular patient case, the Council for International Organizations of Medical Sciences scale was also used to evaluate the probability of the hepatotoxicity being drug related. Objective causality assessment with this scale revealed a probable adverse drug event. Conclusion: Idiopathic valproic acid-induced hepatotoxicity was suspected in a 32-year-old female with a history of sickle cell anemia and cerebral palsy following improvement of transaminitis and abdominal pain on discontinuation of valproic acid therapy and exclusion of an underlying etiology. This case reveals the clinical significance of prompt pharmacist identification and management of the potential adverse drug event.