Design, Analysis, and Pitfalls of Clinical Trials Using Ex Situ Liver Machine Perfusion: The International Liver Transplantation Society Consensus Guidelines

2021 ◽  
Vol 105 (4) ◽  
pp. 796-815 ◽  
Author(s):  
Paulo N. Martins ◽  
Michael D. Rizzari ◽  
Davide Ghinolfi ◽  
Ina Jochmans ◽  
Magdy Attia ◽  
...  
2020 ◽  
Vol 40 (03) ◽  
pp. 264-281 ◽  
Author(s):  
E. Bonaccorsi-Riani ◽  
I.M.A. Brüggenwirth ◽  
J.E. Buchwald ◽  
S. Iesari ◽  
P.N. Martins

AbstractMachine perfusion (MP) preservation is potentially one of the most significant improvements in the field of liver transplantation in the last 20 years, and it has been considered a promising strategy for improved preservation and ex situ evaluation of extended criteria donor (ECD) organs. However, MP preservation adds significant cost and logistical considerations to liver transplantation. MP protocols are mainly classified according to the perfusion temperature with hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) being the two categories most studied so far. After extensive preclinical work, MP entered the clinical setting, and there are now several studies that demonstrated feasibility and safety. However, because of the limited quality of clinical trials, there is no compelling evidence of superiority in preservation quality, and liver MP is still considered experimental in most countries. MP preservation is moving to a more mature phase, where ongoing and future studies will bring new evidence in order to confirm their superiority in terms of clinical outcomes, organ utilization, and cost-effectiveness. Here, we present an overview of all preclinical MP studies using discarded human livers and liver MP clinical trials, and discuss their results. We describe the different perfusion protocols, pitfalls in MP study design, and provide future perspectives. Recent trials in liver MP have revealed unique challenges beyond those seen in most clinical studies. Randomized trials, correct trial design, and interpretation of data are essential to generate the data necessary to prove if MP will be the new gold standard method of liver preservation.


2019 ◽  
Vol 103 (10) ◽  
pp. 2003-2011
Author(s):  
Arash Nickkholgh ◽  
Mohammadsadegh Nikdad ◽  
Saeed Shafie ◽  
Sepehr Abbasi Dezfouli ◽  
Arianeb Mehrabi ◽  
...  

2021 ◽  
Vol 2 (2) ◽  
pp. 149-161
Author(s):  
Rebecca Panconesi ◽  
Mauricio Flores Carvalho ◽  
Matteo Mueller ◽  
Philipp Dutkowski ◽  
Paolo Muiesan ◽  
...  

Although machine perfusion is a hot topic today, we are just at the beginning of understanding the underlying mechanisms of protection. Recently, the first randomized controlled trial reported a significant reduction of ischemic cholangiopathies after transplantation of livers donated after circulatory death, provided the grafts were treated with an endischemic hypothermic oxygenated perfusion (HOPE). This approach has been known for more than fifty years, and was initially mainly used to preserve kidneys before implantation. Today there is an increasing interest in this and other dynamic preservation technologies and various centers have tested different approaches in clinical trials and cohort studies. Based on this, there is a need for uniform perfusion settings (perfusion route and duration), and the development of general guidelines regarding the duration of cold storage in context of the overall donor risk is also required to better compare various trial results. This article will highlight how cold perfusion protects organs mechanistically, and target such technical challenges with the perfusion setting. Finally, the options for viability testing during hypothermic perfusion will be discussed.


2021 ◽  
Vol 7 (3) ◽  
pp. e666
Author(s):  
Adam M. Thorne ◽  
Veerle Lantinga ◽  
Silke Bodewes ◽  
Ruben H. J. de Kleine ◽  
Maarten W. Nijkamp ◽  
...  

2018 ◽  
Vol 17 (5) ◽  
pp. 387-391 ◽  
Author(s):  
Jun-Jun Jia ◽  
Jian-Hui Li ◽  
Hao Yu ◽  
Yu Nie ◽  
Li Jiang ◽  
...  

2019 ◽  
Vol 70 (1) ◽  
pp. 203-205 ◽  
Author(s):  
Vincent Erwin de Meijer ◽  
Masato Fujiyoshi ◽  
Robert Jack Porte

2008 ◽  
Vol 291 (6) ◽  
pp. 735-740 ◽  
Author(s):  
Katrien Vekemans ◽  
Qiang Liu ◽  
Jacques Pirenne ◽  
Diethard Monbaliu

2017 ◽  
Vol 23 (5) ◽  
pp. 679-695 ◽  
Author(s):  
Hazel Marecki ◽  
Adel Bozorgzadeh ◽  
Robert J. Porte ◽  
Henri G. Leuvenink ◽  
Korkut Uygun ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Nikolaos Serifis ◽  
Rudy Matheson ◽  
Daniel Cloonan ◽  
Charles G. Rickert ◽  
James F. Markmann ◽  
...  

Although efforts have been made by transplant centers to increase the pool of available livers by extending the criteria of liver acceptance, this practice creates risks for recipients that include primary non-function of the graft, early allograft dysfunction and post-operative complications. Donor liver machine perfusion (MP) is a promising novel strategy that not only decreases cold ischemia time, but also serves as a method of assessing the viability of the graft. In this review, we summarize the data from liver machine perfusion clinical trials and discuss the various techniques available to date as well as future applications of machine perfusion. A variety of approaches have been reported including hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP); the advantages and disadvantages of each are just now beginning to be resolved. Important in this effort is developing markers of viability with lactate being the most predictive of graft functionality. The advent of machine perfusion has also permitted completely ischemia free transplantation by utilization of in situ NMP showed promising results. Animal studies that focus on defatting steatotic livers via NMP as well as groups that work on regenerating liver tissue ex vivo via MP. The broad incorporation of machine perfusion into routine clinical practice seems incredible.


2021 ◽  
Vol 8 ◽  
Author(s):  
Joseph A. Attard ◽  
Daniel-Clement Osei-Bordom ◽  
Yuri Boteon ◽  
Lorraine Wallace ◽  
Vincenzo Ronca ◽  
...  

Background:Ex situ donor liver machine perfusion is a promising tool to assess organ viability prior to transplantation and platform to investigate novel therapeutic interventions. However, the wide variability in donor and graft characteristics between individual donor livers limits the comparability of results. We investigated the hypothesis that the development of a split liver ex situ machine perfusion protocol provides the ideal comparative controls in the investigation of machine perfusion techniques and therapeutic interventions, thus leading to more comparable results.Methods: Four discarded human donor livers were surgically split following identification and separation of right and left inflow and outflow vessels. Each lobe, on separate perfusion machines, was subjected to normothermic perfusion using an artificial hemoglobin-based oxygen carrier solution for 6 h. Metabolic parameters as well as hepatic artery and portal vein perfusion parameters monitored.Results: Trends in hepatic artery and portal vein flows showed a general increase in both lobes throughout each perfusion experiment, even when normalized for tissue weight. Progressive decreases in perfusate lactate and glucose levels exhibited comparable trends in between lobes.Conclusion: Our results demonstrate comparability between right and left lobes when simultaneously subjected to normothermic machine perfusion. In the pre-clinical setting, this model provides the ideal comparative controls in the investigation of therapeutic interventions.


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