Evaluation of risk for atherosclerosis in Alagille syndrome and progressive familial intrahepatic cholestasis: two congenital cholestatic diseases with different lipoprotein metabolisms.

Abstract

To evaluate the risk for atherosclerosis in Alagille syndrome (AGS) and progressive familial intrahepatic cholestasis (PFIC) on the basis of lipoprotein metabolism and by ultrasonography. Five patients with AGS and 5 with PFIC, ages 3 to 4 years, were enrolled. Intimal-medial thickness and wall stiffness of the common carotid artery were examined by ultrasonography. Serum levels of lipids and lipoproteins were determined. Further, the chemical composition of LDL and its ability to transform macrophages into foam cells were determined. Intimal-medial thickness and wall stiffness were increased in patients with PFIC but not in patients with AGS. Total cholesterol, LDL cholesterol, HDL cholesterol, and lipoprotein X were remarkably increased in patients with AGS, whereas in patients with PFIC, an increase in triglyceride and a decrease in HDL cholesterol were the prominent findings. However, despite the normal LDL cholesterol level, oxidized LDL level was strikingly high in patients with PFIC. LDLs from patients with PFIC had high TG contents and exhibited high abilities to transform macrophages into foam cells. These findings suggest that patients with PFIC are at high risk for cardiovascular disorders involving atherosclerosis.