The effect of portacaval shunt on hepatic lipoprotein metabolism in familial hypercholesterolemia.

The hyperlipidemia observed in familial hypercholesterolemia can be reduced by portacaval anastomosis. We report the effects of a portacaval shunt on hepatic morphology and biosynthetic pathways crucial to hepatic cholesterol homeostasis in homozygous receptor-negative familial hypercholesterolemia. Portacaval anastomosis was associated with a dramatic change in hepatocyte morphology, 28% reduction in plasma low-density lipoprotein concentration, and a decrease in hepatic total and free cholesterol content by 27 and 75%, respectively. Furthermore, the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase was decreased by 56%. Finally, the reduced binding of low-density lipoproteins to hepatic membranes preoperatively was increased following the portacaval shunt. These combined results indicate that the changes in circulating lipoprotein concentrations observed after portacaval shunt are due to alterations in the metabolic consequences of the defective recognition of low-density lipoproteins by the liver of familial hypercholesterolemic subjects.