肝移植在儿童单基因遗传病中的疗效分析

发布时间：2018-04-17 08:08

本文选题：儿童肝移植 + 单基因遗传病　；参考：《上海交通大学》2015年博士论文

【摘要】：目的:儿童单基因遗传病(Monogenic diseases,MDs)主要指由于单基因突变引起的遗传病,可导致患儿器官功能受损、代谢紊乱和发育滞后等临床表现,甚至死亡。I类MDs中突变基因主要表达在肝脏中,其有害代谢产物在肝脏积累并引起肝损,从而导致肝硬化、肝衰甚至肝癌,全身其他脏器较少受累。肝移植广泛应用于I类MDs的治疗中,其可以纠正代谢紊乱并解除继发性肝病。本研究旨在分析和总结儿童肝移植治疗MDs的最佳手术时间、总体生存率、手术疗效及术后并发症等相关情况方法:本研究回顾性分析我中心自2006年10月至2014年12月期间因单基因遗传病接受肝移植治疗儿童的临床资料,选取Alagille综合征(AGS,6名)、糖原累积症Ia型(GSD Ia,5名)、酪氨酸血症I型(HTI,4名)和进行性家族性肝内胆汁淤积症(PFIC,6名)四种常见MDs,共21名患儿(15男6女),平均年龄6.18岁,其中1名接受经典原位肝移植手术治疗,20名接受活体肝移植手术治疗,供体均为患儿父母。分别分析患儿疾病的临床表现,诊断方法和术前治疗方案等相关情况,并对肝移植治疗MDs的最佳手术时间、总体生存率、手术疗效及术后随访等进行分析讨论。结果:肝移植可以有效的纠正MDs的代谢紊乱表现,恢复全身正常脏器功能,患儿术后1年生存率达90%以上,且生活质量明显提高。MDs患儿接受肝移植的主要指征为严重的代谢紊乱伴发育滞后、终末期肝病或者存在肝癌可能。1名GSD Ia型患儿接受经典原位肝移植后1月因移植物抗宿主免疫排斥反应死亡,1名AGS患儿接受活体肝移植后2周因持续性腹腔感染死亡,其余患儿均存活至今。存活患儿术后肝肾功能均恢复正常,生长发育迟缓得以纠正,追长现象明显,社会活动能力达到正常同龄儿童水平,且无严重并发症出现。同时,接受了活体肝移植术的患儿均未出现供肝相关的代谢异常,供体父母术后均恢复良好并出院,无严重并发症出现。结论:肝移植尤其是活体肝移植是治疗I类MDs的有效手段,可以有效纠正患儿代谢紊乱和肝功能异常,并取得良好的近期生存率。对MDs的准确诊断和合适的治疗方案是影响MDs患儿长期预后的关键,对于术前存在肾功能不全或其他脏器先天发育异常患儿,术后仍应密切监测肾功能及相关脏器情况。
[Abstract]:Objective: Monogenic disease (MDS) in children mainly refers to the hereditary diseases caused by monogenic mutations, which can lead to organ dysfunction, metabolic disorder and developmental retardation in children.Even the mutational genes in death class I MDs are mainly expressed in the liver, and their harmful metabolites accumulate in the liver and cause liver damage, which leads to liver cirrhosis, liver failure and even liver cancer, and other organs of the whole body are less involved.Liver transplantation is widely used in the treatment of class I MDs, which can correct metabolic disorder and relieve secondary liver disease.The purpose of this study was to analyze and summarize the optimal operative time and overall survival rate of liver transplantation in children with MDs.Methods: this study retrospectively analyzed the clinical data of children receiving liver transplantation for single gene hereditary disease from October 2006 to December 2014.Six patients with Alagille syndrome, five patients with type Ia of glycogen accumulation, 4 patients with tyrosinemia type I and 6 patients with progressive familial intrahepatic cholestasis were selected.One patient received classic orthotopic liver transplantation and 20 received live liver transplantation.The clinical manifestations, diagnostic methods and preoperative treatment were analyzed, and the optimal operation time, overall survival rate, operative effect and postoperative follow-up of liver transplantation for MDs were analyzed and discussed.Results: liver transplantation could effectively correct the metabolic disorder of MDs and restore the normal organ function of the whole body. The 1 year survival rate of the children was more than 90%.The main indications of liver transplantation in children with higher quality of life were severe metabolic disorder and delayed development.One patient died of graft versus host immune rejection in 1 month after classic orthotopic liver transplantation and one patient died of persistent intraperitoneal infection 2 weeks after living donor liver transplantation in patients with end-stage liver disease or hepatocellular carcinoma.The rest survived until now.After operation, the liver and kidney function recovered, the growth retardation was corrected, the ability of social activities reached the normal level of children of the same age, and no serious complications occurred.At the same time, the donor liver related metabolic abnormalities were not found in all the children receiving live liver transplantation, the donor parents recovered well and were discharged from hospital after operation, and no serious complications occurred.Conclusion: liver transplantation, especially in vivo liver transplantation, is an effective method for the treatment of class I MDs. It can effectively correct metabolic disorders and liver dysfunction in children, and obtain a good short-term survival rate.Accurate diagnosis and appropriate treatment of MDs is the key to long-term prognosis of MDs children. For children with renal insufficiency or other organ congenital dysplasia before operation, renal function and related organs should be closely monitored after operation.
【学位授予单位】：上海交通大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R726.5

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