Extending the Ex Vivo Viability of Transplant Organs Using Normothermic Conditions

Abstract

Liver-related disease is a significant health issue globally, accounting for approximately 2 million deaths per year. In the most extreme cases such as end-stage liver disease, the only treatment is liver transplantation. Public health trends, such as an ageing population and rising obesity, are limiting the use of this treatment, increasing demand for transplants and reducing the supply of donated viable organs. This has led to the increasing use of extended criteria donor livers. However, these are known to result in generally worse transplant outcomes.

New technology is required to expand the donor pool, aimed at repairing and regenerating livers before transplantation. This will “retrieve” a large number of the donated livers that are currently discarded, returning them to viability. The core challenge, however, is that the biological processes involved in repairing and regenerating human livers are known to take place over a period of days and weeks.

While short-term normothermic machine perfusion of livers is well-established clinically, defined here as perfusion for a period of less than 24 hours, its primary benefit is improved assessment of livers prior to transplantation. Currently, no long-term normothermic machine perfusion systems are available commercially, meaning the critical solution of organ repair and regeneration has not yet been translated clinically.

This study builds on previous work undertaken by the research team at Royal Prince Alfred Transplant Institute, who developed a long-term normothermic perfusion model for livers that had successfully kept split livers alive for up to 13 days. The current work contributes automated management of critical system parameters, improving system stability and lowering human labour costs. Data from the successful perfusion of five human livers are presented, including a liver maintained ex vivo in a viable state for transplant for three weeks, longer than any organ recorded in the research literature.