Clarke George, Mao Jingwen, Hann Angus, Fan Yiyu, Gupta Amita, Nutu Anisa, Buckel Schaffner Erwin, Kayani Kayani, Murphy Nicholas, Bangash Mansoor N, Casey Anna L, Wootton Isla, Lawson Alexander J, Dasari Bobby V M, Perera M Thamara P R, Mergental Hynek, Afford Simon C
Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK.
Birmingham Biomedical Research Centre, National Institute for Health Research (NIHR), University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK.
Commun Med (Lond). 2024 Oct 24;4(1):214. doi: 10.1038/s43856-024-00636-2.
Normothermic machine perfusion of donor livers has become standard practice in the field of transplantation, allowing the assessment of organs and safe extension of preservation times. Alongside its clinical uses, there has been expanding interest in extended normothermic machine perfusion (eNMP) of livers as a potential vehicle for medical research. Reproducible extended normothermic machine perfusion has remained elusive due to its increased complexity and monitoring requirements. We set out to develop a reproducible protocol for the extended normothermic machine perfusion of whole human livers.
Human livers declined for transplantation were perfused using a blood-based perfusate at 36 °C using the Liver Assist device (XVIVO, Sweden), with continuous veno-venous haemofiltration in-parallel. We developed the protocol in a stepwise fashion.
Perfusion techniques utilised included: targeted physiological vascular flows, phosphate replacement (to prevent hypophosphataemia), N-acetylcysteine (to prevent methaemoglobin accumulation), and the utilisation of sodium lactate as both a nutritional source and real-time measure of hepatocyte function. All five human livers perfused with the developed protocol showed preserved function with a median perfusion time of 168 h (range 120-184 h), with preserved viability throughout.
Livers can be reproducibly perfused in excess of 120 (range 121-184) hours with evidence of preserved hepatocyte and cholangiocyte function.
供体肝脏的常温机器灌注已成为移植领域的标准做法，有助于评估器官并安全延长保存时间。除了其临床应用外，作为医学研究的潜在载体，对肝脏进行延长常温机器灌注（eNMP）的兴趣也在不断增加。由于其复杂性和监测要求的提高，可重复的延长常温机器灌注一直难以实现。我们着手制定一种可重复的全人肝脏延长常温机器灌注方案。
使用基于血液的灌注液，在36°C下，使用肝脏辅助装置（瑞典XVIVO公司）对因移植而被拒绝的人肝脏进行灌注，并并行连续静脉-静脉血液滤过。我们逐步制定了该方案。
所采用的灌注技术包括：靶向生理性血管流量、磷酸盐替代（以预防低磷血症）、N-乙酰半胱氨酸（以预防高铁血红蛋白积聚）以及利用乳酸钠作为营养来源和肝细胞功能的实时指标。按照所制定的方案灌注的所有五个人肝脏均显示功能得以保留，中位灌注时间为168小时（范围为120 - 184小时），且全程活力得以保留。
肝脏可以被重复灌注超过120（范围为121 - 184）小时，并有肝细胞和胆管细胞功能保留的证据。
