A Case of Acute Liver Failure Following Initiation of Valproic Acid

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Introduction: Valproic acid (VPA), an anticonvulsant used in the treatment of seizure disorders, migraines, and bipolar disorder, has been shown to cause drug-induced liver injury (DILI) in 5-10% of individuals. Effects can range from subclinical transaminase elevations to acute liver failure and death. Herein, we report a case of acute liver failure 18 days following initiation of VPA. Case Report: A 39 year-old woman with a history of a seizure disorder and schizophrenia treated with olanzapine presented to an outside hospital with breakthrough seizures. She was successfully treated with an anti-epileptic regimen including phenytoin, levetiracetam, VPA and lacosamide and discharged. Two days later she was readmitted to our institution with altered mental status and incontinence. Physical exam revealed orientation only to self, flat affect, and icteric sclera. Labs were significant for pH 7.1, lactate 7.1, AST 282, ALT 343, total bilirubin 2.2 and INR 1.1. A non-contrast head CT was normal. She was treated with IV fluids and IV bicarbonate, and was admitted to the medical ICU. By hospital day 5, her labs revealed AST 2129, ALT 1625 and INR 2.4. Initial serologic testing, including levels for acetaminophen, salicylates, alcohol and carbamazepine, a viral hepatitis panel, toxicology screen, anti-mitochondrial antibody, anti-smooth muscle antibody, HIV, CMV, EBV, HSV, RPR, VZV, and AFP, was negative. A transjugular liver biopsy (Figure) was consistent with VPA induced hepatotoxicity. Despite discontinuing all anti-epileptic medications and initiating IV carnitine, the patient developed ventilator-dependent respiratory failure and acute kidney injury requiring hemodialysis and was listed for liver transplantation. Several weeks following the termination of VPA, the patient's liver associated enzymes and renal function normalized. The patient experienced a recurrent seizure and was restarted on levetiracetam prior to being discharged on hospital day 83. Discussion: The absence of other risk factors, the livery biopsy histology, and the timing of liver injury and recovery are all consistent with VPA-induced acute liver failure. A Roussel Uclaf Causality Assessment Method score of 8 was calculated. The mechanism of toxicity is thought to be due to impairment of liver mitochondrial function. Treatment with VPA requires a high index of suspicion for DILI and early discontinuation of this medication may spare patients from liver transplantation or death.Figure 1