A poor-quality human liver was repaired inside a machine for 3 days before it was successfully transplanted into a cancer patient with advanced cirrhosis who otherwise had a "near zero" chance of getting a liver in time, according to a new report.
The liver was kept inside a machine that simulated some functions of the human body before it was successfully transplanted. The 62-year-old patient who received it quickly returned to a normal quality of life and after 1 year had no signs of liver damage, according to the report published in Nature Biotechnology.
“Our therapy shows that by treating livers in the perfusion machine, it is possible to alleviate the lack of functioning human organs and save lives,” Pierre-Alain Clavien, MD, with the University Hospital in Zürich, Switzerland, said in a press release.
Expanding the Viability Window
Livers for transplant are routinely preserved in a static cold solution and implanted within a few hours. Most centers limit the time in the cold solution to 12 hours as the organ's viability drops quickly after that time.
This procedure not only gave the medical team time to resolve some of the issues with the damaged liver, but it also opens up the possibility of turning transplants from emergency to elective surgeries.
"This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure," Clavien and colleagues wrote in the report.
The Liver4Life team, made up of physicians, engineers, and biochemists, developed the complex perfusion machine, which replicates human body functions: A pump mimics the heart, an oxygenator replaces the lungs, and a dialysis unit performs as kidneys would. Hormone and nutrient infusions take over the work of the intestines and pancreas. The machine also moves the liver to the rhythm of simulated breathing.
The team had to overcome multiple barriers that limit the usefulness for any solid organ outside the body over a few hours like the breakdown of red blood cells, stable blood flow, and optimal glucose levels in the liver.
Additionally, because the organ would be maintained by a machine for several days, the scientists also had to address the risk of tissue death.
History Behind the Procedure
The process started in 2015 with the support of the Wyss Zürich Translational Center, one the study's main contributors, which developed the machine used in the procedure to long-term to increases the survival of injured liver graft.
As part of the agreement from the Swiss regulatory authority the process would be used only if the organ was rejected by all transplant centers, the recipient had no other options for a donor liver.
On May 19, 2021, the team was offered a liver graft from a 29-year-old female donor who was battling a bacterial infection and had a tumor in one part of the liver.
It was refused by all other centers because of these multiple problems. The team removed the liver, and the graft was connected to the Wyss perfusion device which maintained it near normal body temperature after 4 hours of cold preservation.
A 62-year-old man on the official national transplant list, had earlier agreed to be considered for receiving a liver graft preserved outside the body in the Wyss machine.
The patient, who had advanced cirrhosis and liver cancer, was fully informed about the process and the presence of a benign tumor in the graft and accepted the transplantation procedure.
Recipient Had 'Near-Zero' Chance to Get a Liver in Time
The authors wrote that the patient had "a near-zero chance to receive a graft in time."
For patients like this man, the wait for liver transplant is longer than a year and no living-donor options were available. The operation took about 6 hours, and he left the hospital after 12 days.
Because a biopsy showed no detectable liver injury from the time in the machine or organ rejection by the man, the researchers were able to choose chose a reduced regimen of immune-suppressing treatment which they tapered off 6 weeks after surgery.
"In our experience, the absence or very low degree of reperfusion injury seen in our transplant is observed only in living donation, where 'close-to-perfect' livers from healthy young donors are transplanted immediately as both donors and recipient are operated in parallel,” the authors wrote.
In the press release, the team said the next step is to evaluate the procedure in other patients in a multicenter study.