Objective: To investigate the impact of orthotopic liver transplantation on serum lipid and growing development in patients with homozygous (HoFH) or compound heterozygotes (cHeFH) familial hypercholesterolemia. Methods: Patients who were treated in Peking Union Medical College Hospital from August 2019 to August 2021, entered the rare disease database and underwent liver transplantation, were included in this single center retrospective cohort study. The height for age Z score (HAZ) and length for age Z score (WAZ) at birth, at the time of transplantation and one year after transplantation were calculated respectively by collecting demographic characteristics, clinical manifestations, echocardiography, lipid-lowering treatment, blood lipid level data and donor characteristics data of liver transplantation. The serum cholesterol level and growing development changes before and after liver transplantation were evaluated. Results: A total of five patients with HoFH or cHeFH, including two females, were included in this study. The median age was 10 years (6-22 years). The median follow up duration was 28 months (24-33 months). All HoFH or cHeFH patients in this study received the maximum daily dosage of the lipid-lowering drug combined with low salt and low-fat diet control treatment for at least 3 months before orthotopic liver transplantation. The average level of total cholesterol (TC) decreased by 27% compared with that before treatment, the level of low-density lipoprotein cholesterol (LDL-C) decreased by 21% after 3 months treatment. There was no intervention of lipid-lowering therapy after operation. One month after liver transplantation, the average levels of TC and LDL-C further decreased rapidly by 68% and 76% respectively. One year after liver transplantation, the level of LDL-C decreased from (17.1±1.6)mmol/L without any intervention before transplantation to (3.0±0.7)mmol/L, and remained stable thereafter. In addition, compared with no intervention before liver transplantation, the serum triglyceride (TG) level decreased after the maximum daily dosage of the lipid-lowering drug and low salt and low-fat diet control for 3 months ((1.88±0.27) mmol/L vs. (1.12±0.55)mmol/L, P=0.031), and the HDL-C level also decreased significantly ((1.95±0.49)mmol/L vs. (0.95±0.30)mmol/L, P=0.006) at the same time period. TG and HDL-C remained stable after liver transplantation during the 24-month follow-up period (P>0.05). One and two years after liver transplantation, there was no significant difference in height and weight, malnutrition and growth retardation between the patients in this cohort and Chinese children of the same age. Conclusion: Early liver transplantation is a feasible and effective treatment option for HoFH or cHeFH patients with extremely high serum low-density lipoprotein cholesterol levels.
目的： 探讨同种原位肝移植对家族性高胆固醇血症纯合型或复合杂合型患者血清胆固醇及生长发育的影响。 方法： 本研究为单中心回顾性队列研究，纳入2019年8月至2021年8月于北京协和医院就诊，进入罕见病数据库并进行同种原位肝移植的家族性高胆固醇血症纯合型（HoFH）或复合杂合型（cHeFH）患者。收集人口统计学特征、临床表现、影像学结果、降脂治疗方式、血脂水平及基因检测结果数据，分别计算出生时、移植时、移植后1年和2年的年龄身高Z评分（HAZ）、年龄体重Z评分（WAZ），并采用t检验评估肝移植术前后血脂水平及生长发育Z评分变化。 结果： 本研究纳入HoFH或cHeFH患者5例，其中，女性2例。中位年龄为10岁（6~22岁），中位随访时间为28个月（24~33个月）。在同种原位肝移植术前进行了可耐受最大剂量降脂药物治疗和低盐低脂饮食方案至少3个月后，总胆固醇（TC）平均水平较未治疗前下降27%，其中低密度脂蛋白胆固醇（LDL-C）平均水平下降21%。肝移植后1个月TC及LDL-C平均水平分别下降了68%和76%，肝移植术后24个月的LDL-C水平已从术前未经任何干预的（17.1±1.6）mmol/L下降至（3.0±0.7）mmol/L，并保持稳定。与肝移植术前未干预相比，血清甘油三酯（TG）水平在进行最大药物剂量及低盐低脂饮食控制后降低［（1.88±0.27）mmol/L比（1.12±0.55）mmol/L，P=0.031］，同期HDL-C水平也明显下降［（1.95±0.49）mmol/L比（0.95±0.30）mmol/L，P=0.006］，而TG及HDL-C在肝移植术后共随访24个月期间差异均无统计学意义（P均>0.05）。患者术后未再进行任何降脂治疗。术后1年及2年WAZ和HAZ与中国同年龄阶段儿童标准值相比差异无统计学意义，无营养不良和生长发育迟缓表现。 结论： 早期同种原位肝移植对极高LDL-C水平的HoFH或cHeFH患者是一种可行、有效的治疗方法。.