Portacaval shunt and liver transplantation in treatment of familial hypercholesterolemia.

Portacaval shunt surgery and liver transplantation have been used to treat patients with severe familial hypercholesterolemia (FH). These operations have usually been performed on patients with homozygous FH, but portacaval shunt surgery has also been used in several patients with the heterozygous form of the disease. Portacaval shunt surgery lowers the low density lipoprotein (LDL) cholesterol level by 25% or more in about 80% of patients. The main effect of the operation is to lower the LDL apolipoprotein (apo) B-100 production rate, but there is little effect on the fractional rate of clearance of this apolipoprotein. The operation is only palliative because significant hypercholesterolemia remains after surgery. Liver transplantation restores LDL receptor activity to over 60% of normal, which results in an increase in the fractional catabolic rate (FCR) and a decrease in the synthetic rate of LDL apo B-100. Both metabolic changes cause the LDL cholesterol level to drop by about 80%. After transplantation, homozygotes are also more responsive to certain cholesterol-lowering drugs. It is concluded that liver transplantation is more effective than portacaval shunt surgery for treating homozygous FH. However, liver transplantation should be reserved for those patients who cannot produce functioning LDL receptors and who do not respond to more conservative forms of therapy.