For patients with liver failure, the wait for a new liver can be long.
Most of the time, a transplant can’t take place until a suitable liver from a deceased donor is found. And even then, the liver only remains viable for a short time after being removed from the donor.
The countdown for transferring the liver from donor to recipient starts the moment it’s removed from the donor’s body, resulting in a race against the clock to transport the organ to the facility where it will be transplanted.
Now, however, new technologies to maintain organs in a warm, functioning state during transit are extending this window and increasing the supply of available livers that can be used for transplant. The new method, ex vivo normothermic machine perfusion (also called warm perfusion), has been used at UCLA Health since November 2022, shortly after it was approved by the Food and Drug Administration.
(Another method, partial liver donation from a living donor, is less common: Fewer people opt to be living donors, and those who do must be deemed suitable candidates for the operation. The organ also must be compatible with the intended recipient.)
Limitations of cold storage
Donated livers from deceased donors have traditionally been transported via cold storage, which meant being placed in a cooler and maintained at a temperature of 4 degrees Celsius (39.2 degrees Fahrenheit) during transit. In this near-freezing state, livers can last up to 10 to 12 hours outside of the human body. After that, however, ischemia (the lack of blood circulation) and the resulting lack of oxygen and nutrients increases the risk of damage.
“During cold ischemia, there’s no oxygen going to the organ, there’s no blood flow, there’s no nutrients,” explained , chief of the department of liver and pancreas transplantation at UCLA Health and professor of surgery at the David Geffen School of Medicine at UCLA. “All we’re doing is slowing the metabolic activity to just the bare minimum to keep it functional while we’re preparing it for transplant.”
This method, also known as “ice box storage” or “static cold storage,” was the standard for decades. It preserved the organs in a temporary static state, allowing them to be transported. Even so, the method could only be used for the subset of available livers that were deemed suitable for transplant, and for a limited timeframe, before the organ would start to degrade.
Warm perfusion
Unlike cold storage, warm perfusion keeps the liver in a functional condition mirroring that of the human body by pumping it with warm oxygenated blood that’s 37 degrees Celsius (98.6 degrees Fahrenheit).
The technology that enables warm perfusion was first developed for donated hearts, which can only last for six to eight hours via cold storage, and was subsequently expanded to be used for lungs, which have a viability window of eight to 12 hours in a cooled state.
UCLA Health played a leading role in the FDA clinical trials evaluating warm perfusion for both heart and lung transplantation and has continued to use the technology for both since its subsequent FDA approval and to participate in additional FDA trials.
Making more liver transplants possible
In addition to lengthening the viability window for a donated liver, keeping the organ in a warm, functioning state prior to transplantation has other benefits. The first is helping to expand the pool of donated livers, for which demand has long exceeded supply.
Most livers for transplant have traditionally come from patients who have been declared brain-dead and had previously agreed to be donors (or whose family has authorized the donation). With donations following brain death, the organ to be donated is still in a functioning state, Dr. Farmer explained.
However, the vast majority of people die by what’s known as circulatory death (sometimes called cardiac death), in which their heart permanently ceases functioning. In this scenario, all circulation stops, and all of the other functions of the body, including the organs, cease as well.
The complications when using a liver from a circulatory death donor traditionally have been significantly higher, Dr. Farmer explained, which meant that even though the patient may have wished to be a donor, the liver often wasn’t considered usable.
In particular, a liver obtained after circulatory death carries a high likelihood of ischemic cholangiopathy, or bile duct injury, when transplanted into a new recipient.
“Ischemic cholangiopathy would happen in less than 1% of cases with brain-dead donors but in 30 to 50% of cases with circulatory death donors,” Dr. Farmer said. “So, people were very hesitant to use circulatory death donors, because if you get a biliary duct injury in the person who receives the liver, the liver would fail and they’d need another transplant.”
As a result, Dr. Farmer explained, “We became very restrictive on the types of circulatory death patients we would take organs from. We were passing for good reason, because it was a high risk, but people would wait on the waiting list longer, and death rates on the waiting list would be longer. And yet, every day we had patients dying circulatory deaths and families wanting to donate, and we would say no.”
There was a very small subset of livers from circulatory death donors that could be used, Dr. Farmer explained, but even so there was still a 10% risk of ischemic cholangiopathy for the recipient.
Using warm perfusion has dramatically reduced this risk to 1%, so that a liver from someone who’s died a circulatory death now has the same ischemic cholangiopathy risk as one from a brain-dead donor. In 2024, machine perfusion was used for 59 transplants at UCLA Health. Of these, 23 were circulatory death donors and the balance were brain-dead donors.
When to use warm perfusion
With perfusion technology still being relatively new, the UCLA Liver Transplant Program is using it in transplant scenarios that might otherwise carry potential additional risks, Dr. Farmer said.
A subset of livers for donation “are really good organs and can use any mechanism of storage,” he explained. “We tend to use traditional cold, static storage on those.”
As an example, for a liver from a young donor with no risk factors that can be transplanted in under 12 hours, “there’s really no sense in putting it on the machine,” he said.
In other cases, there may be livers available that have potential risk factors, which is where warm perfusion offers clear benefits as a way to vet the organs prior to transplant. These risk factors include advanced age, as well as “a litany of other factors,” Dr. Farmer said.
In these scenarios, the transplant team will first resuscitate the liver using warm perfusion so they can assess how well it functions.
“If it works, you can go ahead and transplant,” he said. “And if it doesn’t work, you can discard it. It makes the organs much safer for the recipient, and it also allows us to use certain organs that we know carry a risk factor, because it mitigates that risk.”
Another key consideration: the organ’s intended recipient. “Certain patients require more surgical time to remove their liver and be able to sew the new liver in,” Dr. Farmer explained. This might be the case for a patient who’s undergoing more than one procedure, such as a coronary bypass as well as a liver transplant, or for a patient who’s had a previous transplant, which takes more time to remove. In these situations, warm perfusion of the liver extends the time window and keeps the liver as functional as possible.
Dr. Farmer characterized warm perfusion as “a revolutionary technology” that’s likely to expand in usage.
“We’re getting to the point where we’re trying to look at other higher-risk donors to see if we can make the organ safer by putting on the machine,” he said. With warm perfusion, “we can resuscitate the organ and stabilize the cellular function outside of someone’s body. And then when you transplant it, it’s a better organ.”
