The occurrence of intramitochondrial Ca2+ granules in valproate-induced liver injury.

Two epileptic patients treated with anticonvulsants of valproic acid, phenobarbital, nitrazepam, and diphenylhydantoin developed anorexia, convulsions, and unconsciousness. The liver biopsy samples showed degenerated hepatocytes containing enlarged mitochondria with a distorted matrix. The matrix granules in the mitochondria were enlarged in size as compared with those of chronic hepatitis (Po = 0.0009). X-ray microanalysis has revealed the presence of calcium in large mitochondrial matrix granules. Both patients were thought to have valproic acid intoxication because they recovered quickly after the withdrawal of valproic acid.