Changes induced in human liver by long-term anticonvulsant therapy. Functional and ultrastructural data

The study reports functional and morphological findings in eight male subjects undergoing anticonvulsant therapy for periods from 20 days up to 15 years. All subjects showed an increased activity of the hepatic microsomal NADPH cytochrome c reductase and an increased amount of smooth membranes in hepatocytes. The enzymatic activity was higher in the first years of treatment. Quantitative ultrastructural analysis showed that a twofold increase of the smooth membranes of hepatocytes had already been reached after 20 days of therapy, with a modest additional increase occurring thereafter. Both enzymatic and structural changes appear to be related to therapy. In addition, abnormal lipofuscin-related cytoplasmic formations were present in the hepatocytes of five subjects. Such formations are thought to represent an accumulation of abnormal degradation products, possibly related to an interaction of the drug(s) metabolites with cellular components.