Laufende Studie

HOPE for the Liver

Hypothermic Oxygenated liver machine PErfusion (HOPE) – Better organ quality saves lifes

Concept of Hypothermic Oxygenated liver PErfusion (HOPE)

PrincipleIn an attempt to improve preservation of liver grafts, the concept of endischemic hypothermic oxygenated machine liver perfusion presents a simple, efficient and practical strategy to be used exclusively after organ transport at the site of organ transplantation.

Following standard back table preparation the provided disposable connects the liver with the perfusion machine (ECOPS system in human settings), which is a simple approach, since perfusion, done while recipient hepatectomy, proceeds exclusively over the portal vein. Importantly, during 1 to 2 hours of perfusion portal pressure needs to be constantly monitored, aiming for values below 3 mmHg. Furthermore, the perfusate recquires full saturation with oxygen, while perfusate and liver temperature is maintained between 4 and 10 ° C. After hepatectomy of the recipient the perfused graft is disconnected and transplanted.

Protective MechanismThe mechanisms of protection by hypothermic machine perfusion appear to be twofold.

First, oxygenation under hypothermic conditions protects from mitochondrial and nuclear injury by down regulation of mitochondrial activity before reperfusion. After 1 hour of perfusion, mitochondrial respiration appears significantly reduced in the presence of an oxygenated perfusate, suggesting that more than 1 h of HOPE treatment may not become necessary.

Second, cold perfusion itself, under low pressure conditions (≤ 3mmHg), cleans glycocalix and endothel, while preventing endothelial damage. Therefore, one h HOPE in the transplant center, during recipient hepatectomy is enough, indiciating a very good liver function after reperfusion (Ref.: Schlegel A, de Rougemont O, Graft R, Clavien PA, Dutkowski P. Protective mechanism of end-ischemic cold machine perfusion in DCD liver grafts.

Publications
  • Philipp Dutkowski et al. Hypothermic oxygenated machine perfusion (HOPE) down-regulates the immune response in a rat model of liver transplantation. Ann Surg 2014; 260(5): 931-938.
  • Philipp Dutkowski, Pierre A. Clavien et al.First Comparison of Hypothermic Oxygenated Perfusion (HOPE) Versus Static Cold storage of Human DCD Liver Transplants – An International Matched Case Analysis. Ann Surg 2015; 262: 764-771.
Website

Hypothermic Oxygenated liver PErfusion (HOPE)      >>  Homepage (Swiss National fonds Project)


Human Trial  –  Study Design
Hypothermic Oxygenated liver PErfusion (HOPE)

To test machine liver perfusion against standard cold storage before liver transplantation.

The suggested study will demonstrate, for the first time, in a randomized trial the effect of a highly simplified endischemic perfusion technique in human liver grafts in terms of graft dysfunction and biliary injury. In case of convincing success, we postulate a high acceptance rate among transplant surgeons, since this approach can be easily applied in any centre worldwide.

Study design – The study population consist of patients undergoing liver transplantation (University Hospital Zürich, Switzerland).

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