Celik Neslihan, Squires James E, Soltys Kyle, Vockley Jerry, Shellmer Diana A, Chang Wonbae, Strauss Kevin, McKiernan Patrick, Ganoza Armando, Sindhi Rakesh, Bond Geoffrey, Mazariegos George, Khanna Ajai
Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh of UPMC Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine Pittsburgh Pennsylvania.
Pediatric Hepatology Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania.
JIMD Rep. 2019 Jun 19;48(1):83-89. doi: 10.1002/jmd2.12053. eCollection 2019 Jul.
Domino liver transplantation (DLT) involves transplanting liver from a patient with metabolic disease into a patient with end-stage liver disease with the expectation that the recipient will not develop the metabolic syndrome or the recurrent syndrome will have minimal affect. The domino donor gets a deceased donor or a segment of live-donor liver through the deceased donor organ allocation system. Waitlist mortality for the domino recipient exceeds morbidity associated with getting the donor disease. Between 2015 and 2017, four patients with three metabolic disorders at UPMC Children's Hospital of Pittsburgh underwent DLT with domino allografts from maple syrup urine disease (MSUD) patients. These included patients with propionic acidemia (PA) (n = 1), Crigler-Najjar (CN) syndrome type-1 (n = 2), and carbamoyl phosphate synthetase deficiency (CPSD) (n = 1). Mean follow-up was 1.6 years (range 1.1-2.1 years). Total bilirubin levels normalized postoperatively in both CN patients and they maintain normal allograft function. The PA patient had normal to minimal elevations of isoleucine and leucine, and no other abnormalities on low protein diet supplemented with a low methionine and valine free formula. No metabolic crises have occurred. The patient with CPSD takes normal baby food. No elevation in ammonia levels have been observed in any of the patients. DLT for a select group of metabolic diseases alleviated the recipients of their metabolic defect with minimal evidence of transferrable-branched chain amino acid elevations or clinical MSUD despite increased protein intake. DLT using allografts with MSUD expands the live donor liver pool and should be considered for select metabolic diseases that may have a different enzymatic deficiency.
多米诺肝移植(DLT)是指将患有代谢性疾病患者的肝脏移植给终末期肝病患者,期望受者不会发生代谢综合征或复发性综合征的影响最小。多米诺供体通过已故供体器官分配系统获得已故供体或活体供肝的一部分。多米诺受者的等待名单死亡率超过了患供体疾病的发病率。2015年至2017年期间,匹兹堡大学医学中心儿童医院的4例患有3种代谢紊乱的患者接受了来自枫糖尿症(MSUD)患者的多米诺同种异体肝移植。其中包括丙酸血症(PA)患者(n = 1)、1型克里格勒 - 纳贾尔(CN)综合征患者(n = 2)和氨甲酰磷酸合成酶缺乏症(CPSD)患者(n = 1)。平均随访时间为1.6年(范围1.1 - 2.1年)。两名CN患者术后总胆红素水平恢复正常,且同种异体肝移植功能保持正常。PA患者异亮氨酸和亮氨酸水平正常至轻度升高,在补充低蛋氨酸和无缬氨酸配方的低蛋白饮食下无其他异常。未发生代谢危机。CPSD患者食用正常婴儿食品。所有患者均未观察到氨水平升高。对于一组特定的代谢性疾病进行DLT可减轻受者的代谢缺陷,尽管蛋白质摄入量增加,但可转移的支链氨基酸升高或临床MSUD的证据很少。使用MSUD同种异体移植物进行DLT扩大了活体供肝库,对于可能存在不同酶缺乏的特定代谢性疾病应考虑采用。