Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China.
Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing, China.
Transplant Rev (Orlando). 2021 Jan;35(1):100592. doi: 10.1016/j.trre.2020.100592. Epub 2020 Dec 18.
Background-objectives: Liver transplantation (LT) and combined liver and kidney transplantation (CLKT) have been proposed as enzyme replacement therapies for methylmalonic aciduria (MMA). We aimed to synthesize the available evidence on their safety and efficacy.
Medline, Embase and Cochrane library were searched to identify studies that reported post-LT/CLKT clinical outcomes of MMA from their inception to February 1, 2020. The pooled rate was calculated using random-effects model with Freeman-Tukey double arcsine transformation method.
Thirty-two studies involving 109 patients were included. The pooled estimate rates were 99.9% (95% CI 95.3-100.0) for patient survival, 98.5% (95% CI 91.5-100.0) for graft survival after LT/CLKT. The combined incidence of biliary, vascular complications and rejection were 0.2% (95% CI 0.0-6.6), 7.7% (95% CI 0.1-22.1) and 18.4% (95% CI 4.6-36.3), respectively. The pooled estimate rates were 100.0% (95% CI 99.4-100.0) for metabolic eradication, 61.5% (95% CI: 33.4-87.0) for normalization of kidney function. Chronic kidney disease (CKD) remission is more promising after CLKT (70.3% VS 37.6% in LT group). The pooled estimate rates for neurodevelopmental status improvement and protein intake liberalization were 52.0% (95% CI 2.8-98.8) and 36.3% (95% CI 6.3-71.7), respectively.
This first quantitative systematic review confirms favorable survival outcomes and partially improved disease-related complications in transplanted MMA patients, although some results should be interpreted with caution. Future studies with detailed description of long-term outcomes and consensus on neurodevelopmental evaluation method can help provide a more accurate picture.
肝移植（LT）和肝肾联合移植（CLKT）已被提议作为甲基丙二酸血症（MMA）的酶替代疗法。我们旨在综合现有证据评估其安全性和疗效。
从建库至 2020 年 2 月 1 日，检索 Medline、Embase 和 Cochrane 图书馆，以确定报道 MMA 患者 LT/CLKT 后临床结局的研究。采用随机效应模型和 Freeman-Tukey 双反正弦变换法计算汇总率。
纳入 32 项研究共 109 例患者。LT/CLKT 后患者存活率、移植物存活率的汇总估计率分别为 99.9%（95%CI 95.3-100.0）、98.5%（95%CI 91.5-100.0）。胆管、血管并发症和排斥反应的合并发生率分别为 0.2%（95%CI 0.0-6.6）、7.7%（95%CI 0.1-22.1）和 18.4%（95%CI 4.6-36.3）。代谢清除率的汇总估计率为 100.0%（95%CI 99.4-100.0），肾功能正常化的汇总估计率为 61.5%（95%CI：33.4-87.0）。CLKT 后慢性肾脏病（CKD）缓解更有希望（LT 组为 37.6%，CLKT 组为 70.3%）。神经发育状态改善和蛋白质摄入放宽的汇总估计率分别为 52.0%（95%CI 2.8-98.8）和 36.3%（95%CI 6.3-71.7）。
本项首次定量系统评价证实，移植 MMA 患者具有良好的生存结局，部分改善了疾病相关并发症，但部分结果应谨慎解读。未来需要更详细地描述长期结局，并就神经发育评估方法达成共识，以提供更准确的结果。
