Liver transplantation continues to evolve as strategies expand to address organ shortage and optimize outcomes. Normothermic machine perfusion (NMP) offers a novel way to preserve and assess donor livers prior to implantation. In this episode of Behind the Knife, our transplant team at University of Nebraska Medical Center discusses the latest evidence from randomized trials, practical applications in donation after circulatory death (DCD) grafts, and how NMP is shaping clinical decision-making in high-risk transplants. 

Hosts
-  Madeline Cloonan, MD PhD, General Surgery Resident, University of Nebraska Medical Center, @maddie_cloonan  
- Jacqueline Dauch, MD, Assistant Professor, University of Nebraska Medical Center 
-  Shaheed Merani, MD PhD, Associate Professor, University of Nebraska Medical Center 
- Alan Langnas, DO, Professor, University of Nebraska Medical Center 

Learning Objectives
- Describe the principles of normothermic machine perfusion (NMP) and how it differs from static cold storage. 
- Summarize the design and key outcomes of the PROTECT trial and the Chapman et al. trial on NMP in liver transplantation. 
- Recognize the clinical scenarios where NMP provides the greatest benefit, particularly in high-risk grafts (e.g., DCD donors, high donor risk index). 
- Apply a practical viability assessment framework for livers on NMP, including hemodynamics, bile production, lactate trajectory, and histology when indicated. 
- Discuss the implications of NMP for allocation, system logistics, and future adoption trends in transplantation. 

References
 
1.     Markmann JF, Abouljoud MS, Ghobrial RM, et al. Impact of portable normothermic blood-based machine perfusion on outcomes of liver transplant: the OCS Liver PROTECT randomized clinical trial. JAMA Surg. 2022;157(3):189-198. doi:10.1001/jamasurg.2021.6781. https://pubmed.ncbi.nlm.nih.gov/34985503/

2.     Chapman WC, Barbas AS, D’Alessandro AM, et al. Normothermic machine perfusion of donor livers for transplantation in the United States: a randomized controlled trial. Ann Surg. 2023;278(5):e912-e921. doi:10.1097/SLA.0000000000005934. https://pubmed.ncbi.nlm.nih.gov/37389552/

3.     Nasralla D, Coussios CC, Mergental H, et al; Consortium for Organ Preservation in Europe. A randomized trial of normothermic preservation in liver transplantation. Nature. 2018;557(7703):50-56. doi:10.1038/s41586-018-0047-9. https://pubmed.ncbi.nlm.nih.gov/29670285/

4.     Brubaker AL, Sellers MT, Abt PL, et al. US liver transplant outcomes after normothermic regional perfusion vs standard super rapid recovery. JAMA Surg. 2024;159(6):677-685. doi:10.1001/jamasurg.2024.0520. https://pubmed.ncbi.nlm.nih.gov/38568597/

5.     Wall A, Snoddy M, Du J, et al. The current landscape of in situ and ex situ machine perfusion utilization for liver grafts from cardiac donation after circulatory death donors in the US. Am J Transplant. 2025;25(3):574-582. doi:10.1016/j.ajt.2024.09.012. https://pubmed.ncbi.nlm.nih.gov/39293517/

6.     Watson CJE, Gaurav R, Fear C, Swift L, Selves L, Ceresa CDL, Upponi SS, Brais R, Allison M, Macdonald-Wallis C, Taylor R, Butler AJ. Predicting Early Allograft Function After Normothermic Machine Perfusion. Transplantation. 2022 Dec 1;106(12):2391-2398. doi: 10.1097/TP.0000000000004263. https://pubmed.ncbi.nlm.nih.gov/36044364/

7.     Watson CJE, Hunt F, Messer S, Currie I, Large S, Sutherland A, Crick K, Wigmore SJ, Fear C, Cornateanu S, Randle LV, Terrace JD, Upponi S, Taylor R, Allen E, Butler AJ, Oniscu GC. In situ normothermic perfusion of livers in controlled circulatory death donation may prevent ischemic cholangiopathy and improve graft survival. Am J Transplant. 2019 Jun;19(6):1745-1758. doi: 10.1111/ajt.15241. https://pubmed.ncbi.nlm.nih.gov/30589499/

8.     Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010;16(8):943-949. doi:10.1002/lt.22091.https://pubmed.ncbi.nlm.nih.gov/20677285/ 

9.     Kwong AJ, Kim WR, Lake JR, Schladt DP, Handarova D, Howell J, Schumacher B, Weiss S, Snyder JJ, Israni AK. OPTN/SRTR 2023 Annual Data Report: Liver. Am J Transplant. 2025 Feb;25(2S1):S193-S287. doi: 10.1016/j.ajt.2025.01.022. https://pubmed.ncbi.nlm.nih.gov/39947804/

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