Department of Surgery, Division of Hepato-Pancreato- Biliary and Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Curr Opin Organ Transplant. 2024 Aug 1;29(4):248-254. doi: 10.1097/MOT.0000000000001151. Epub 2024 May 10.
With changing donor characteristics (advanced age, obesity), an increase in the use of extended criteria donor (ECD) livers in liver transplantation is seen. Machine perfusion allows graft viability assessment, but still many donor livers are considered nontransplantable. Besides being used as graft viability assessment tool, ex situ machine perfusion offers a platform for therapeutic strategies to ameliorate grafts prior to transplantation. This review describes the current landscape of graft repair during machine perfusion.
Explored anti-inflammatory therapies, including inflammasome inhibitors, hemoabsorption, and cellular therapies mitigate the inflammatory response and improve hepatic function. Cholangiocyte organoids show promise in repairing the damaged biliary tree. Defatting during normothermic machine perfusion shows a reduction of steatosis and improved hepatobiliary function compared to nontreated livers. Uptake of RNA interference therapies during machine perfusion paves the way for an additional treatment modality.
The possibility to repair injured donor livers during ex situ machine perfusion might increase the utilization of ECD-livers. Application of defatting agents is currently explored in clinical trials, whereas other therapeutics require further research or optimization before entering clinical research.
随着供体特征(年龄较大、肥胖)的变化,肝移植中越来越多地使用扩展标准供体(ECD)肝脏。机器灌注允许评估移植物的活力,但仍有许多供体肝脏被认为不适合移植。除了用作移植物活力评估工具外,离体机器灌注还为在移植前改善移植物的治疗策略提供了一个平台。本综述描述了机器灌注过程中目前的移植物修复情况。
探索抗炎治疗,包括炎症小体抑制剂、血液吸附和细胞治疗,减轻炎症反应并改善肝功能。胆管细胞类器官在修复受损的胆管树方面显示出前景。与未处理的肝脏相比,在常温机器灌注过程中脱脂可减少脂肪变性并改善肝胆功能。在机器灌注过程中摄取 RNA 干扰疗法为另一种治疗方式铺平了道路。
在离体机器灌注过程中修复受损供体肝脏的可能性可能会增加 ECD 肝脏的利用率。目前正在临床试验中探索使用脱脂剂,而其他治疗方法在进入临床研究之前需要进一步研究或优化。