Until now, livers could be stored safely outside the body for only a few hours. With the novel perfusion technology, livers – and even injured livers – can now be kept alive outside of the body for an entire week. This is a major breakthrough in transplantation medicine, which may increase the number of available organs for transplantation and save many lives of patients suffering from severe liver disease or a variety of cancers.
Injured cadaveric livers, initially not suitable for use in transplantation, may regain full function while perfused in the new machine for several days. The basis for this technology is a complex perfusion system, mimicking most core body functions close to physiology.
"The success of this unique perfusion system – developed over a four-year period by a group of surgeons, biologists and engineers – paves the way for many new applications in transplantation and cancer medicine helping patients with no liver grafts available" explains Professor Pierre-Alain Clavien, chair of the department of surgery and transplantation at the University Hospital Zurich (USZ). When the project started in 2015, livers could only be kept on the machine for 12 hours.
The seven-day successful perfusion of poor-quality livers now allows for a wide range of strategies – the repair of pre-existing injury, cleaning of fat deposits in the liver or even regeneration of partial livers.
The Liver4Life project was developed under the umbrella of Wyss Zurich Institute, which brought together the highly specialized technical know-how and biomedical knowledge of experts from the University Hospital Zurich (USZ), ETH Zurich and the University of Zurich (UZH).
"The biggest challenge in the initial phase of our project was to find a common language that would allow communication between the clinicians and engineers," explains Professor Philipp Rudolf von Rohr, professor of process engineering at ETH Zurich and co-leader with Clavien of the study.
The inaugural study shows that six of ten perfused poor-quality human livers, declined for transplantation by all centres in Europe, recovered to full function within one week of perfusion on the machine. The next step will be to use these organs for transplantation. The proposed technology opens a large avenue for many applications offering a new life for many patients with end stage liver disease or cancer.
Abstract
The ability to preserve metabolically active livers ex vivo for 1 week or more could allow repair of poor-quality livers that would otherwise be declined for transplantation. Current approaches for normothermic perfusion can preserve human livers for only 24 h. Here we report a liver perfusion machine that integrates multiple core physiological functions, including automated management of glucose levels and oxygenation, waste-product removal and hematocrit control. We developed the machine in a stepwise fashion using pig livers. Study of multiple ex vivo parameters and early phase reperfusion in vivo demonstrated the viability of pig livers perfused for 1 week without the need for additional blood products or perfusate exchange. We tested the approach on ten injured human livers that had been declined for transplantation by all European centers. After a 7-d perfusion, six of the human livers showed preserved function as indicated by bile production, synthesis of coagulation factors, maintained cellular energy (ATP) and intact liver structure.
Authors
Dilmurodjon Eshmuminov, Dustin Becker, Lucia Bautista Borrego, Max Hefti, Martin J Schuler, Catherine Hagedorn, Xavier Muller, Matteo Mueller, Christopher Onder, Rolf Graf, Achim Weber, Philipp Dutkowski, Philipp Rudolf von Rohr, Pierre-Alain Clavien
[link url="https://www.sciencedaily.com/releases/2020/01/200113111147.htm"]University of Zurich material[/link]
[link url="https://www.nature.com/articles/s41587-019-0374-x"]Nature Biotechnology abstract[/link]