肝脏移植治疗纯合型家族性高胆固醇血症的研究进展  

Research progress of liver transplantation for patients with homozygous familial hypercholesterolemia

作　　者：赵量 温军 郭远林[1] ZHAO Liang;WEN Jun;GUO Yuanlin(Chinese Academy of Medical Sciences&Peking Union Medical College&Endocrinology and Cardiovascular Metabolism Center,Fuwai Hospital,Beijing 100037,China)

机构地区：[1]中国医学科学院北京协和医学院阜外医院内分泌与心血管代谢中心,北京市100037

出　　处：《中国动脉硬化杂志》2021年第4期353-358,共6页Chinese Journal of Arteriosclerosis

基　　金：中国心血管健康联盟“2017进•阶研究基金”(T2018-ZX010)。

摘　　要：家族性高胆固醇血症(FH)是一种常染色体遗传代谢性疾病,患者血清中低密度脂蛋白胆固醇(LDLC)水平显著升高,导致早发动脉粥样硬化性心血管疾病(ASCVD)。未经治疗的纯合型家族性高胆固醇血症(HoFH)患者多因动脉粥样硬化性心血管疾病于30岁前死亡。HoFH的降胆固醇治疗包括治疗性生活方式改变、降脂药物治疗、血脂净化和肝脏移植等。降脂药物对HoFH的治疗效果十分有限,血脂净化费用昂贵、有创、需要每1~2周一次的维持,患者依从性差,难以长期应用。90%以上的FH为低密度脂蛋白受体(LDLR)基因突变所致,LDLR主要位于肝脏细胞,肝脏是代谢低密度脂蛋白(LDL)的主要场所。因此,肝脏移植能够实现对功能异常LDLR的替代,是一种纠正胆固醇代谢异常的有效方法。本文主要就肝脏移植的安全性与有效性、目前存在的挑战,应用肝脏移植治疗HoFH的前景进行综述。Familial hypercholesterolemia(FH)is an autosomal dominant inherited metabolic disorder,patient with FH has an elevated serum low density lipoprotein cholesterol(LDLC)and a high incidence of premature atherosclerotic cardiovascular disease(ASCVD).If untreated,patients with homozygous familial hypercholesterolemia(HoFH)develop premature death by the age of 30 years,generally from ASCVD.Cholesterol-lowing therapies for HoFH include therapeutic lifestyle changes,lipid-lowing pharmacologic therapy,lipid apheresis and liver transplantation,etc.However,the curative effect of the traditional lipid-lowering drugs is still very limited in HoFH population.It is difficult to carry out lipid apheresis constantly because of its high cost,invasiveness,long-term maintenance at weekly or biweekly interval and poor adherence.Nearly 90%of FH is caused by mutations in the LDL receptor(LDLR)gene.Since L DLR are located mainly in the hepatocytes,liver transplantation achieves the replacement of dysfunctional hepatic LDLR,and it is considered to be the effective way to correct hepatic cholesterol metabolism.This paper mainly review the efficacy and safety of liver transplantation,current challenges and the prospect of liver transplantation for HoFH.

关 键 词：纯合型家族性高胆固醇血症 肝脏移植 动脉粥样硬化性心血管疾病 

分 类 号：R5[医药卫生—内科学]