Abstract
More than 20 deaths due to hepatotoxicity associated with VPA have occurred in the USA. We report 2 autopsied cases of fatal hepatotoxicity associated with VPA. In both cases the signs of hepatotoxicity appeared after 3-4 weeks VPA therapy and in 1 case consisted of persistent elevation of serum phenytoin (PHT) level for 5 days despite stopping VPA and PHT. By light microscopy, the liver showed nodular architecture with pseudoductular proliferation of periportal hepaocytes in both cases. The remaining pericentral liver cells had a granular cytoplasm which on electron microscopy in 1 case was due to closely packed mitochondria. Fat globules were seen in some cells but the appearance was clearly distinct from that in Reye syndrome.
The earliest laboratory signs of VPA hepatotoxicity were derangements of hepatic synthetic and/or detoxification processes. The transaminases in our patients overlapped those in epileptic children without serious toxicity. Other parameters are needed to predict which patients might develop fatal hepatotoxicity. Unexplained fluctuations of anticonvulsant levels might be an early sign of significant VPA toxicity.
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Taylor, D., Deschryver, K., Keating, J. et al. 1614 FATAL VALPROIC ACID (VPA) HEPATOTOXICITY. Pediatr Res 15 (Suppl 4), 712 (1981). https://doi.org/10.1203/00006450-198104001-01631
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DOI: https://doi.org/10.1203/00006450-198104001-01631
