Selzner Markus, Goldaracena Nicolas, Echeverri Juan, Kaths Johan M, Linares Ivan, Selzner Nazia, Serrick Cyril, Marquez Max, Sapisochin Gonzalo, Renner Eberhard L, Bhat Mamatha, McGilvray Ian D, Lilly Leslie, Greig Paul D, Tsien Cynthia, Cattral Mark S, Ghanekar Anand, Grant David R
Departments of Surgery, Toronto General Hospital, Toronto, Ontario, Canada.
Departments of Medicine, Toronto General Hospital, Toronto, Ontario, Canada.
Liver Transpl. 2016 Nov;22(11):1501-1508. doi: 10.1002/lt.24499.
The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non-US Food and Drug Administration-approved, bovine-derived, gelatin-based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin-based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique. Ten liver grafts were perfused for 480 minutes (340-580 minutes). All livers cleared lactate (final lactate 1.46 mmol/L; 0.56-1.74 mmol/L) and produced bile (61 mL; 14-146 mL) during perfusion. No technical problems occurred during perfusion, and all NEVLP-preserved grafts functioned well after LT. NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1-3 without reaching significance. No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio (1.1 [1-1.56] versus 1.1 [1-1.3]; P = 0.5) and bilirubin (1.5; 1-7.7 mg/dL versus 2.78; 0.4-15 mg/dL; P = 0.5). No difference was found in the duration of intensive care unit stay (median, 1 versus 2 days; range, 0-8 versus 0-23 days; P = 0.5) and posttransplant hospital stay (median, 11 versus 13 days; range, 8-17 versus 7-89 days; P = 0.23). Major complications (Dindo-Clavien ≥ 3b) occurred in 1 patient in the NEVLP group (10%) compared with 7 (23%) patients in the CS group (P = 0.5). No graft loss or patient death was observed in either group. Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT. Using US Food and Drug Administration-approved Steen solution will avoid a potential regulatory barrier in North America. Liver Transplantation 22 1501-1508 2016 AASLD.
一项欧洲试验正在研究常温体外肝脏灌注（NEVLP）作为肝移植（LT）的一种保存技术，该试验使用了聚明胶肽，这是一种未获美国食品药品监督管理局批准的、源自牛的、基于明胶的灌注溶液。我们报告了一项使用基于人白蛋白的Steen溶液的NEVLP安全性和可行性临床研究。将10例在Metra设备上于37°C用Steen溶液灌注、外加3单位红细胞的人肝移植物的移植结果，与30例采用冷保存（CS）作为保存技术的匹配历史对照组进行比较。10例肝移植物灌注了480分钟（340 - 580分钟）。所有肝脏在灌注期间清除了乳酸（最终乳酸水平为1.46 mmol/L；0.56 - 1.74 mmol/L）并产生了胆汁（61 mL；14 - 146 mL）。灌注期间未出现技术问题，所有经NEVLP保存的移植物在肝移植后功能良好。在术后第1 - 3天，NEVLP组与CS组相比，天冬氨酸转氨酶和丙氨酸转氨酶值较低，但未达到显著差异。通过第7天的国际标准化比值（1.1 [1 - 1.56] 对 1.1 [1 - 1.3]；P = 0.5）和胆红素（1.5；1 - 7.7 mg/dL对2.78；0.4 - 15 mg/dL；P = 0.5）测量，未检测到NEVLP组和CS组移植物术后功能的差异。在重症监护病房住院时间（中位数，1天对2天；范围，0 - 8天对0 - 23天；P = 0.5）和移植后住院时间（中位数，11天对13天；范围，8 - 17天对7 - 89天；P = 0.23）方面未发现差异。NEVLP组有1例患者（10%）发生了严重并发症（Dindo - Clavien≥3b），而CS组有7例患者（23%）发生（P = 0.5）。两组均未观察到移植物丢失或患者死亡。使用Metra设备并采用Steen溶液进行常温体外灌注保存肝脏是安全的，且肝移植后的结果与CS相当。使用美国食品药品监督管理局批准的Steen溶液将避免在北美可能出现的监管障碍。《肝脏移植》22 1501 - 1508 2016美国肝脏病研究协会
