Bilheimer D W
Department of Internal Medicine, University of Texas Health Science Center, Dallas 75235.
Arteriosclerosis. 1989 Jan-Feb;9(1 Suppl):I158-63.
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.
门腔分流术和肝移植已被用于治疗重度家族性高胆固醇血症（FH）患者。这些手术通常在纯合子FH患者身上进行，但门腔分流术也已应用于数例杂合子形式疾病的患者。门腔分流术可使约80%的患者低密度脂蛋白（LDL）胆固醇水平降低25%或更多。该手术的主要作用是降低LDL载脂蛋白（apo）B-100的生成率，但对这种载脂蛋白的清除率影响很小。该手术只是姑息性的，因为术后仍存在显著的高胆固醇血症。肝移植可使LDL受体活性恢复至正常的60%以上，这导致LDL apo B-100的分解代谢率（FCR）增加，合成率降低。这两种代谢变化都会使LDL胆固醇水平下降约80%。移植后，纯合子对某些降胆固醇药物也更敏感。得出的结论是，肝移植在治疗纯合子FH方面比门腔分流术更有效。然而，肝移植应仅用于那些无法产生有功能的LDL受体且对更保守治疗形式无反应的患者。
