Organ transplants are usually done in a hurry, as donor organs quickly become damaged outside the body. Now, however, researchers have managed to keep a donor liver alive for several days by machine. During this time, they were able to treat the organ, which was previously unsuitable for transplantation, with medication and thus make it healthy again. The patient to whom they then transplanted the prepared organ is still doing well a year later.
In the case of a liver transplant, the donor organ is usually cooled down to two to five degrees Celsius immediately after removal from the body, so that the damage caused by the lack of supply outside the body is limited. Nevertheless, the liver must be transplanted within less than twelve hours. In this case, there is no time for more detailed examinations of the liver tissue or even medical treatment. Many livers from potential organ donors therefore have to be discarded as unsuitable for transplantation. Many potential donor organs have also been ruled out due to previous illnesses or liver tumors.
Damaged donor liver
A team led by Pierre-Alain Clavien from the University Hospital Zurich kept such a sorted donor liver alive outside the body for three days with the help of machines and treated it during this time in such a way that it could be transplanted to a cancer patient in May 2021. The patient was able to leave the hospital a few days after the operation and has been doing well ever since, the researchers now report after a one-year follow-up period.
The transplanted liver came from a 29-year-old patient who, before her death, suffered from sepsis caused by multidrug-resistant bacteria. In addition, there was an approximately four centimeter large tumor of unclear nature in the liver. “This potential liver transplant was rejected by all other centers, mainly because it required a diagnostic work-up of the liver damage, which was not immediately possible, and because of the donor’s ongoing sepsis with multidrug-resistant microorganisms,” the authors report.
treatment in the machine
However, Clavien’s team took care of the severely damaged liver. In January 2020, the team presented a self-developed perfusion machine for the first time, which makes it possible to keep potential donor livers alive outside the body at body temperature for several days. They inserted the donor’s liver into this machine. The machine imitates the human body as closely as possible: a pump serves as a replacement heart, an oxygenator replaces the lungs and a dialysis unit replaces the kidneys. In addition, numerous hormone and nutrient infusions take over the functions of the intestine and pancreas. Like the diaphragm in the human body, the machine also moves the liver to the rhythm of human breathing.
While the liver was being cared for in the machine, the researchers treated it with numerous medications, including broad-spectrum antibiotics against the multi-resistant germs. In addition, they took samples of the tumor tissue and determined that it was a benign tissue growth that was not an obstacle to transplantation. Both the treatment and the examination would not have been possible without the mechanical care of the liver.
Liver transplanted successfully
As part of an approved individual treatment attempt, the researchers then transplanted the prepared donor liver to a 62-year-old patient who was suffering from advanced liver cirrhosis and recurrent liver cancer. “Due to my rapidly progressing tumor, I had little chance of getting a liver from the waiting list within a reasonable period of time,” reports the patient. Therefore, he consented to the experimental transplant. The man survived the operation with only minor blood loss and his body accepted the new liver well. One year after the transplantation, the patient is still doing well and the liver is showing good functional values, as the doctors report.
“Our therapy shows that treating livers in the perfusion machine can alleviate the lack of functioning donor organs and save lives,” says Clavien. In the future, the researchers want to test the procedure on other patients and demonstrate its safety and effectiveness with clinical studies. At the same time, they are developing the next generation of perfusion machines and are investigating other ways of treating liver diseases outside the body.
Source: Pierre-Alain Clavien (University Hospital Zurich) et al., Nature Biotechnology, doi: 10.1038/s41587-022-01354-7