Machine Perfusion: Cold versus Warm, versus Neither. Update on Clinical Trials

Abstract

Machine 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.

Heterogeneous indications and the need for viability assessment: An international survey on the use of machine perfusion in liver transplantation

“…Indeed, early studies have assessed feasibility of MP in a clinical setting or compared MP with SCS. No study comparing different MP techniques head‐to‐head has been published so far 28 . However, results of a large, multicenter study comparing end‐ischemic normothermic versus end‐ischemic hypothermic oxygenated MP from Germany are expected and will hopefully shed some light on the respective benefits and shortcomings of each technique.…”

Implementation and design of customized ex vivo machine perfusion. Analysis of its first results

“…The portal flow obtained was around 50 mL/min/100 g, similar to that reported by others. 19,22,23 It is important to consider that the hyper-flow and excessive dilation of portal vein and hepatic artery is detrimental, generating endothelial disruption and alteration of the vascular architecture. 24 Stable hemodynamic parameters provide adequate conditions for optimal graft recovery and long preservation time.…”

“…The perfusion system was stable and determined by target physiological pressures as has been described by other authors. 15,16,19,20 Flows progressively increased until stabilization as a consequence of targeted pressures. We believe it is mainly due to self-regulation of the hepatic tissue and progressive recruitment of the vascular territory primarily contracted by hypoperfusion, decreased temperature, and vasoconstrictor factors due to associated ischemia.…”

Designer organs: The future of personalized transplantation

“…In light of the donor organ shortage, the research and surgical communities have been motivated to discover novel organ protective strategies to solve this crisis. Previous areas of investigation include pharmacologic methods of graft treatment such as preservation solution additives (i.e., antioxidant and anti‐inflammatory agents) 2 as well as more dynamic and therapeutic approaches including ex situ machine perfusion 3 . However, manipulation of the graft via gene editing and modulation has recently garnered support as a precise method of altering and protecting the graft from damage as well as conferring favorable qualities to suboptimal organs to ensure that they can be transplanted with acceptable outcomes.…”

“…including ex situ machine perfusion. 3 However, manipulation of the graft via gene editing and modulation has recently garnered support as a precise method of altering and protecting the graft from damage as well as conferring favorable qualities to suboptimal organs to ensure that they can be transplanted with acceptable outcomes.…”