Liver ex situ machine perfusion preservation: A review of the methodology and results of large animal studies and clinical trials

Abstract

Ex vivo machine perfusion (MP) is a promising way to better preserve livers prior to transplantation. Currently, no methodology has a verified benefit over simple cold storage. Before becoming clinically feasible, MP requires validation in models that reliably predict human performance. Such a model has been found in porcine liver, whose physiological, anatomical, and immunological characteristics closely resemble the human liver. Since the 1930s, researchers have explored MP as preservation, but only recently have clinical trials been performed. Making this technology clinically available holds the promise of expanding the donor pool through more effective preservation of extended criteria donor (ECD) livers. MP promises to decrease delayed graft function, primary nonfunction, and biliary strictures, which are all common failure modes of transplanted ECD livers. Although hypothermic machine perfusion (HMP) has become the standard for kidney ex vivo preservation, the precise settings and clinical role for liver MP have not yet been established. In research, there are 2 schools of thought: normothermic machine perfusion, closely mimicking physiologic conditions, and HMP, to maximize preservation. Here, we review the literature for porcine ex vivo MP, with an aim to summarize perfusion settings and outcomes pertinent to the clinical establishment of MP. Liver Transplantation 23 679-695 2017 AASLD.

The ultrastructural characteristics of porcine hepatocytes donated after cardiac death and preserved with warm machine perfusion preservation

“…The relatively high level of the LDH and AST in perfusate of MMP suggest that the considerable hepatocellular damage exist even in the more protective method, MMP in this study. The warm MP with rewarming is promising, as more and more researchers are publishing results preferring these temperature settings [82]. However it has not been sufficiently defined the rewarming velocity of liver grafts, the critical temperature the liver should reach, and the period of warm MP needed to adjust metabolic parameters [82].…”

“…The warm MP with rewarming is promising, as more and more researchers are publishing results preferring these temperature settings [82]. However it has not been sufficiently defined the rewarming velocity of liver grafts, the critical temperature the liver should reach, and the period of warm MP needed to adjust metabolic parameters [82]. Therefore, it is necessary that our morphological analysis should be done on the more protective modified WMP to clarify the protective mechanism of the MP on the liver graft in future.…”

Gene Silencing With siRNA (RNA Interference): A New Therapeutic Option During Ex Vivo Machine Liver Perfusion Preservation

“…In addition to HMP, normothermic machine perfusion (NMP) allows for viability assessment of the organ prior to transplantation. Hemodynamic, synthetic, and metabolic parameters can be used to assess the viability of the graft . Administering chemically stabilized siRNA (2’O‐methylation) leads to cellular uptake of the siRNA by the hepatocytes .…”

Implementing an innovated preservation technology: The American Society of Transplant Surgeons’ (ASTS) Standards Committee White Paper on Ex Situ Liver Machine Perfusion

“…Dr. At the present time three main types of devices are being evaluated in clinical trials in the United States and abroad: hypothermic machine perfusion using oxygenated perfusate (HOPE), hypothermic nonactively oxygenated perfusion (HMP), and normothermic machine perfusion (NMP) 5,6,28,29 (Table 1). 26 Although rapidly gaining acceptance and interest, machine liver preservation is still in its infancy.…”