亲属活体肝移植治疗儿童甲基丙二酸血症30例的临床分析

Clinical analyses of living donor liver transplantation for methylmalonic acidemia in children

目的探讨亲属活体肝移植治疗儿童甲基丙二酸血症(MMA)的临床疗效。方法回顾性总结2016年11月至2019年4月30例MMA患儿接受活体肝移植的临床资料以及术后并发症发生情况和中期随访结果,30例受者中,男性20例(66.7%),女性10例(33.3%),移植时中位年龄为2岁9个月(6个月~12岁4个月),身高和体重中位数分别为87 cm(61~137 cm)和11.0 kg(7.0~29.0 kg);术前Child-Pugh分级均为A级;移植物质量与受者体重比(GRWR)中位数为2.1%(1.0%~3.2%)。供者均为携带致病基因的杂合子父亲或母亲。结果30例儿童受者均为维生素B12无效型,术后中位随访时间为18个月(6~34个月),均未再发生严重不可耐受的代谢性酸中毒失代偿。与术前相比,术后3个月血丙酰肉碱与丙酰肉碱/乙酰肉碱比值均明显下降,尿甲基丙二酸与3-羟基丙酸水平均显著降低。术后发生外科并发症4例(13.3%),包括1例肝动脉血栓,1例胆道并发症,1例肝静脉并发症,以及1例肠穿孔。术后患者生存率与移植物生存率分别为100%与96.3%。结论使用杂合子父母供肝的亲属活体肝移植治疗MMA可显著降低代谢性酸中毒失代偿的发生风险,并明显改善患儿的生存质量。

Objective To explore the clinical efficacy of living donor liver transplantation(LDLT)for children with methylmalonic acidemia(MMA).Methods From November 2016 to April 2019,clinical data,perioperative outcomes,complications and mid-term follow-up data of 30 MMA children receiving LDLT were retrospectively analyzed.Results All recipients were vitamin B12-ineffective.There were 20 boys(66.7%)and 10 girls(33.3%)with a median age of 33(6-144)months at transplantation.And the median values of height and body weight were 87(61-137)cm and 11.0(7.0-29.0)kg respectively.The median graft-to-recipient weight ratio was 2.1%(1.0%-3.2%).All of them belonged to Child-Pugh class A.All donors were biological parents as a heterozygous carrier of pathogenic gene.Surgical complications occurred in 4 cases(13.3%),including hepatic artery thrombosis(n=1),biliary complications(n=1),hepatic vein complications(n=1)and intestinal perforation(n=1).The median follow-up period was 18(6-34)months.The posttransplant survival rates of patients and grafts were 100%and 96.3%respectively.No severe intolerable decompensated metabolic acidosis occurred after transplantation.Compared with pre-transplantation,the levels of propionylcarnitine and the ratios of propionylcarnitine to acetylcarnitine in blood and levels of methylmalonic acid and 3-hydroxypropionic acid in urine decreased markedly at 3 months post-transplantation.Conclusions LDLT using grafts from parental donors as a heterozygous carrier for MMA can significantly reduce the risks of decompensated metabolic acidosis and greatly improve the quality-of-life of children.