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Hepatotoxicity as a result of valproic acid therapy is well documented. Elevation in aminotransferase activities is rarely associated with symptoms. It sometimes manifests as acute liver failure. Here, we report a 8-year-old girl who was referred for unresolving jaundice and itching for 3 months. Past history revealed afebrile convulsion 5 months previously and beginning of valproic acid treatment. Valproic acid was discontinued after the development of jaundice. Physical examination revealed ichterus, xanthomas on extensor surfaces of extremities, and hepatomegaly without any sign of chronic liver disease. Total and direct bilirubin levels were 20.2 and 12.9 mg/dL, respectively. Enzyme activities indicating cholestasis were increased together with blood cholesterol. Tests for infectious and autoimmune, metabolic, and genetic disorders were not informative. Liver biopsy revealed portal inflammation, severe bile duct loss, and cholestasis. The patient was considered to have valproic acid-associated vanishing bile duct syndrome, which has not been reported previously.

Objective: The aim of this study was to evaluate bone mineral density (BMD) in epileptic children receiving valproic acid (VPA) and to determine differences between osteopenic and non-osteopenic children., Methods: Thirty-three epileptic children, receiving VPA for at least 6 months, were compared with 33 healthy children for BMD. BMD was measured by dual-energy X-ray absorptiometry at lumbar vertebrae, femoral neck and greater trochanter. Serum calcium, phosphorus, alkaline phosphates, osteocalcin and VPA levels were also determined., Results: Patient's osteocalcin levels were significantly higher (P = 0.02) and femur and trochanter BMD values were significantly lower (P = 0.04 and P = 0.03, respectively). Duration of VPA therapy was significantly longer and doses of VPA were significantly higher in seven osteopenic patients compared with 26 non-osteopenic patients. Osteopenic patients (4.6 +/- 2.4 years) were younger than non-osteopenic patients (7.8 +/- 3.2 years) (P = 0.01)., Conclusion: Long-term and high dose VPA therapy may cause osteopenia, primarily in younger epileptic children. These patients should be followed closely by BMD measurements.