Hypothermic Machine Perfusion Prevents Complications in Donated-After-Cardiac-Death Liver Allografts

By Gene Emery

February 25, 2021

(Reuters Health) - When preparing livers for transplant, hypothermic oxygenated machine perfusion (HMP) slashes the odds of nonanastomotic biliary stricture (NAS) by two thirds, cuts the chance of post-reperfusion syndrome by more than half, and lowers the risk of early allograft dysfunction by more than 40% compared to conventional cold storage, according to a European test of 156 recipients.

The study, published online by The New England Journal of Medicine, "provides the first and convincing scientific evidence" of a dramatic difference between the two techniques, senior author Dr. Robert Porte of the University Medical Center Groningen in the Netherlands told Reuters Health in an email. "This is a clinically very relevant finding."

The study involved donors who suffered circulatory death instead of brain death, meaning the livers were exposed to longer warm ischemia times and were three times more likely to develop NAS than livers taken from brain-dead donors.

All the livers were stored and transported in the conventional way -- in a bag with a cold preservation fluid that is packed in ice. But in the experimental group, the liver underwent at least two hours of hypothermic oxygenated perfusion at the end of static cold storage and before implantation.

"Especially the bile ducts of a liver are very susceptible to this warm ischemia, and the injury caused by ischemia-reperfusion during the transplant procedure is the main cause of NAS after transplantation, said Dr. Porte, a transplant surgeon and professor of surgery. "Despite an ongoing organ shortage, many transplant centers (especially in the U.S.) are reluctant to accept such livers for their patients on the waitlist due to the high risk of NAS and subsequent morbidity and risk of early graft loss."

"Now that we have the scientific evidence that the risk of NAS after circulatory death liver transplantation can be reduced significantly, it is expected that more of these livers will be accepted for transplantation," he said.

Not only will hypothermic oxygenated machine perfusion likely become standard for livers taken after circulatory death, the technique will probably be used for other types of livers that might be challenging to transplant, he said.

The new study, known as DHOPE-DCD, was done at six transplant centers. The perfusion was through the portal vein and the hepatic artery, using separate pumps that pulsed at 60 beats per minutes and a fluid kept at 10 degrees C.

Within the first six months after transplant, nonanastomotic biliary strictures occurred in 6% of the patients whose livers were prepared with machine perfusion versus 18% of the patients whose livers received conventional storage (P=0.03).

The rates of postreperfusion syndrome were 12% and 27% respectively.

Early allograft dysfunction was seen in 26% of livers where machine perfusion was used compared with 40% in the conventional storage group.

Dr. Porte said that both hypothermic and normothermic devices are being tested in clinical trials.

"While NMP (the normothermic device) may sound most appealing as the liver is preserved at body temperature, it is more complex and riskier than HMP (the hypothermic device)," he said.

"Although some pilot studies and single center case series have suggested that (oxygenated) HMP reduces the incidence of biliary complications (especially the occurrence of nonanastomotic biliary strictures or NAS) after liver transplantation, formal scientific evidence from a randomized controlled trial was lacking" until this study, said Dr. Porte. "At the same time, studies on NMP have failed to demonstrate a significant reduction in the incidence of NAS."

Doctors are also testing whether hypothermic machine perfusion improves the success of livers obtained from brain-dead donors.

SOURCE: https://bit.ly/3qNiC7z The New England Journal of Medicine, online February 24, 2021.