Long-term normothermic machine perfusion of the liver: a world of opportunities

Liver transplantation is the only curative treatment option for end-stage liver disease. Transplantation requires donor livers, which are scarce. The global shortage of donor organs, coupled with the increasing demand for liver transplantation, has led to a worldwide crisis in transplantation medicine, with a waiting list mortality approaching 20%. This shortage has resulted in the use of donor livers that are at high risk for complications during and after transplantation. Ex situ normothermic machine perfusion for several hours is increasingly used to recondition such livers and assess viability prior to transplantation. However, the organ shortage can be further diminished by extending normothermic machine perfusion to days when damaged, compromised livers can be cured/recovered, rendering them suitable for transplantation. To achieve this, perfusion machines must be adapted to support and maintain liver metabolism and homeostasis. Therefore, the new machine must mimic the human body by replacing the various organ systems, including an artificial kidney, pancreas, heart, and lungs. At the same time, the liver and its surroundings need continuous monitoring and protection. This machine will eventually allow for an increase in the number of donor livers, which will lead to a reduction in waiting list mortality for people with end-stage liver disease. During this PhD research, we laid the foundation for this machine and a protocol to keep donor livers viable and functional for up to 7 days. The next step will be to develop a clinically approved perfusion machine and therapies to heal/repair damaged donor livers.