van Rijn R, Karimian N, Matton A P M, Burlage L C, Westerkamp A C, van den Berg A P, de Kleine R H J, de Boer M T, Lisman T, Porte R J
Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Br J Surg. 2017 Jun;104(7):907-917. doi: 10.1002/bjs.10515. Epub 2017 Apr 10.
Experimental studies have suggested that end-ischaemic dual hypothermic oxygenated machine perfusion (DHOPE) may restore hepatocellular energy status and reduce reperfusion injury in donation after circulatory death (DCD) liver grafts. The aim of this prospective case-control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation.
In consecutive DCD liver transplantations, liver grafts were treated with end-ischaemic DHOPE. Outcome was compared with that in a control group of DCD liver transplantations without DHOPE, matched for donor age, donor warm ischaemia time, and recipient Model for End-stage Liver Disease (MELD) score. All patients were followed for 1 year.
Ten transplantations involving liver grafts treated with DHOPE were compared with 20 control procedures. There were no technical problems. All 6-month and 1-year graft and patient survival rates were 100 per cent in the DHOPE group. Six-month graft survival and 1-year graft and patient survival rates in the control group were 80, 67 and 85 per cent respectively. During DHOPE, median (i.q.r.) hepatic adenosine 5'-triphosphate (ATP) content increased 11-fold, from 6 (3-10) to 66 (42-87) µmol per g protein (P = 0·005). All DHOPE-preserved livers showed excellent early function. At 1 week after transplantation peak serum alanine aminotransferase (ALT) and bilirubin levels were twofold lower in the DHOPE group than in the control group (ALT: median 966 versus 1858 units/l respectively, P = 0·006; bilirubin: median 1·0 (i.q.r. 0·7-1·4) versus 2·6 (0·9-5·1) mg/dl, P = 0·044). None of the ten DHOPE-preserved livers required retransplantation for non-anastomotic biliary stricture, compared with five of 20 in the control group (P = 0·140).
This clinical study of end-ischaemic DHOPE in DCD liver transplantation suggests that the technique restores hepatic ATP, reduces reperfusion injury, and is safe and feasible. RCTs with larger numbers of patients are warranted to assess the efficacy in reducing post-transplant biliary complications.
实验研究表明，缺血末期双低温氧合机器灌注（DHOPE）可能恢复肝细胞能量状态，并减少心脏死亡后供肝（DCD）移植中的再灌注损伤。这项前瞻性病例对照研究的目的是评估DHOPE在DCD肝移植中的安全性和可行性。
在连续的DCD肝移植中，对肝移植供肝采用缺血末期DHOPE处理。将结果与未采用DHOPE的DCD肝移植对照组进行比较，对照组在供体年龄、供体热缺血时间和受体终末期肝病模型（MELD）评分方面相匹配。所有患者随访1年。
对10例采用DHOPE处理肝移植供肝的移植手术与20例对照手术进行了比较。未出现技术问题。DHOPE组所有患者6个月和1年的移植物和患者生存率均为100%。对照组6个月移植物生存率、1年移植物和患者生存率分别为80%、67%和85%。在DHOPE灌注期间，肝组织腺苷三磷酸（ATP）含量中位数（四分位间距）从每克蛋白质6（3 - 10）微摩尔增加11倍至66（42 - 87）微摩尔（P = 0.005）。所有经DHOPE保存的肝脏均显示出良好的早期功能。移植后第1周，DHOPE组血清丙氨酸转氨酶（ALT）峰值和胆红素水平比对照组低两倍（ALT：中位数分别为966和1858单位/升，P = 0.006；胆红素：中位数分别为1.0（四分位间距0.7 - 1.4）和2.6（0.9 - 5.1）毫克/分升，P = 0.044）。10例经DHOPE保存的肝脏中，无一例因非吻合口胆管狭窄需要再次移植，而对照组20例中有5例（P = 0.140）。
这项关于DCD肝移植中缺血末期DHOPE的临床研究表明，该技术可恢复肝脏ATP水平，减少再灌注损伤，且安全可行。有必要开展纳入更多患者的随机对照试验，以评估其在减少移植后胆道并发症方面的疗效。
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