Abstract

Donation after circulatory death (DCD) is a promising solution to the critical shortage of donor graft tissue. Maintaining organ viability after donation until transplantation is essential for optimal graft function and survival. To date, static cold storage is the most widely used form of preservation in clinical practice. However, ischemic damage present in DCD grafts jeopardizes organ viability during cold storage, and whether static cold storage is the most effective method to prevent deterioration of organ quality in the increasing numbers of organs from DCD is unknown. Here we describe the historical background of DCD liver grafts and a new preservation method for experimental and clinical transplantation. To prevent ischemia-reperfusion injury in DCD liver grafts, a hypothermic machine perfusion (HMP) technique has recently been developed and may be superior to static cold preservation. We present evidence supporting the need for improving liver perfusion performance and discuss how doing so will benefit liver transplantation recipients.

Highlights

  • 100,000 patients worldwide undergo organ transplantation annually, but many other patients remain on waiting lists

  • We summarize the historical background of liver transplantation from donation after circulatory death (DCD), the subsequent development of clinical donor criteria for DCD liver grafts, and the progress of machine perfusion (MP) for DCD kidney and liver in cold storage are introduced

  • DCD livers were flushed with warm Ringer’s solution containing streptokinase and a vasodilator prior to simple cold storage (SCS); recipients received glycine, a mitogen activated protein (MAP) kinase inhibitor, α-tocopherol, glutathione, and an iron chelator intravenously. This approach was effective and eliminated primary non-function, improving graft function [45]. In another temperature-associated strategy, we have developed a temperature-controlled preservation machine (Figure 1) and demonstrated beneficial functional recovery in a porcine liver transplantation model after 30 minutes of Donor warm ischemic time (DWIT) plus 4 to 5 hours of total ischemic time in the hypothermic machine perfusion (HMP) group compared with the SCS-only group [46]

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Summary

Introduction

100,000 patients worldwide undergo organ transplantation annually, but many other patients remain on waiting lists. As mandated in the Declaration, each country or region, guided by the ethical principles of the World Health Organization (WHO), should strive to provide a sufficient number of organs for its recipients from its own population [1] In another strategy, the use of marginal donors is a promising way to increase the supply of graft tissue. Controlled Controlled have been reduced considerably due to the use of better selection criteria, livers from controlled DCD, and shorter warm and cold ischemic times Even this improved strategy does not always significantly increase the numbers of potential donors. Additional studies are needed to identify clinical and policy strategies to reduce the incidence and improve the outcome of primary nonfunction and ischemic cholangiopathy in recipients of DCD liver grafts One means to this end is to improve organ preservation methods and techniques. Recipient factors significantly (P ≤0.05) predictive of graft failure included: age 55 years or older; male; African-American; positivity for hepatitis C virus (HCV); presence of metabolic liver disorders; transplant Model for End-stage Liver Disease

Conclusions
Findings
Steering Committee of the Istanbul Summit
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