Treatment of valproic acid-associated hepatic failure with orthotopic liver transplantation

OBJECTIVE: To report a case of valproic acid (VPA)-induced hepatotoxicity and to discuss the incidence rates, risk factors, possible etiologies, preventive measures, and treatment courses for this severe reaction. DATA SOURCES: Case reports, review articles, and relevant laboratory studies identified by MEDLINE. DATA EXTRACTION: Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors. DATA SYNTHESIS: The case of a 23-year-old woman with VPA-associated hepatic failure was successfully treated with orthotopic liver transplantation. Hepatic failure is a rare, often fatal, adverse effect of VPA. Most cases of VPA-associated hepatic failure have occurred within several months of initiation of therapy. Initial symptoms of presentation often include nausea and vomiting, lethargy, or loss of seizure control. Laboratory values to be monitored include serum concentrations of hepatic enzymes, and, in some patients, tests indicative of the liver's synthetic capabilities. The exact mechanism of VPA-associated hepatic failure has not been clearly established; however, it is postulated to involve the formation of toxic metabolites. Major risk factors include age less than two years and concomitant treatment with more than one anticonvulsant. Other significant risk factors include underlying metabolic or serious neurologic disorders. CONCLUSIONS: Caution should be taken when initiating VPA therapy and clinicians should be familiar with the risk factors and clinical presentation of this reaction.