L-Carnitine as Treatment for Valproic Acid Induced Acute Liver Failure

Abstract

Acute Liver Failure (ALF) is defined by the presence of acute liver injury, hepatic encephalopathy and elevated prothrombin time/international normalized ratio (INR) in a patient without cirrhosis or preexisting liver disease, with duration of illness less than 26 weeks. The disease often has a poor outcome. The causes of ALF include drug induced liver injury, viral, ischemic, and autoimmune hepatitis. Valproic acid, a commonly used anticonvulsant, has been associated with ALF in children and adults. A 54 year old African American male was transferred from inpatient psychiatry to the Coronary Care Unit because of acute chest pain and dyspnea secondary to non-ST elevation myocardial infarction complicated by new onset heart failure with reduced ejection fraction. The patient had been admitted to psychiatry for the management of schizophrenia with valproic acid and haldol three months prior to transfer to medicine. One day after the transfer he developed altered mental status. Laboratory tests were notable for elevated ProBNP 3401 pg/ml (normal range (NR) 0-1200), INR 2.59 (NR 0.8-1.2), ammonia 103 Mmol/L (NR 11-32), aspartate transaminase (AST) 8128 U/L (NR 15-37), alanine transaminase (ALT) 5296 U/L (NR 30-65). The patient was moved to the medical intensive care unit with the diagnosis of ALF secondary to valproic acid. An N-acetylcysteine infusion was started as this has been shown to have potential benefit in non-acetaminophen induced ALF. L-carnitine, which has been reported to interrupt the mechanism by which valproic acid causes liver toxicity, was started. The patient showed significant improvement in clinical and laboratory status after 48 hours of N-acetylcysteine drip and 120 hours of L-carnitine treatment. ALF is an uncommon but, known complication of valproic acid, regardless of serum drug levels. It has been reported that early treatment with L-carnitine can be beneficial especially, in cases of severe hepatotoxicity, coma, serum valproic acid levels > 450 mpg/ml or hyperammonemic encephalopathy. Valproic acid combines with carnitine leading to carnitine depletion. Supplementation of L-carnitine is postulated to increase the beta-oxidation of valproic acid, interrupting the mechanism by which valproic acid causes liver toxicity. Although ischemia might have contributed to ALF in this patient, there was a clear improvement within the time frame in which L-carnitine was administered. Therefore, monitoring liver function test is crucial.