Acute hepatic injury in a child with Dravet syndrome: No protective effect of stiripentol

We read with interest the article by Nicolai et al. who described four children with Dravet syndrome treated with valproic acid (VPA) and topiramate (TPM), who all developed transient hepatic injury shortly after introduction of acetaminophen in therapeutic dosage. Based on the time interval between fever, administration of acetaminophen, epileptic status and liver enzyme disturbances, the authors suggested that the accumulation of toxic acetaminophen metabolites due to inhibition of cytochrome P450 enzymes by VPA and TPM was possibly responsible for the hepatotoxicity. We would like to report a similar observation in a 7-year-old girl with Dravet syndrome, who had been on a stable AED regimen of VPA, clobazam and stiripentol for some years. She was admitted after being found by the parents with high fever and sopor which was considered to be due to a postictal state. She was treated with therapeutic dosage of acetaminophen (75 mg/kg/day) to suppress fever. Within 12 h after initiation of acetaminophen therapy, clotting parameters became progressively abnormal (PT 21 s (n < 13 s), APTT 39 s (n < 33 s)) with other liver parameters remaining within normal range except for slightly elevated ASAT (120 U/ l). Twenty-four hours after initiation of acetaminophen biochemical analyses showed LDH 784 U/l, ASAT 1580 U/l, ALAT 372 U/l, total bilirubin 4 mmol/l, albumin 26 g/l, NH3 60 mmol/l, PT 24 s and APTT 42 s. Creatine kinase was also strongly elevated (3354 U/l, n < 50 U/l). Because of suspicion of acetaminophen toxicity, n-acetylcysteine was given twice, even though serum acetaminophen level appeared to be within the therapeutic range (11 mg/l), and acetaminophen was discontinued. Biochemical parameters started to recover within