Can a Nationwide Liver Paired Donation Program Work?

Lucy Hicks

January 30, 2023

For a patient who needs a liver, living donation offers an alternative to staying on a list of over 10,000 people waiting for a liver transplant. But what happens when your donor is not a match? To expand the number of living liver donations in the United States, the United Network for Organ Sharing (UNOS) has launched the first national paired liver donation pilot program in the United States.

"It's an exciting time to be caring for patients who need liver transplants," said Benjamin Samstein, MD, chief of liver transplantation at New York–Presbyterian/Weill Cornell Medical Center, New York City, in an interview with Medscape Medical News. He is also the principal investigator for the UNOS pilot program. "I do believe it is within our grasp to make sure that nobody dies while waiting for an organ," he said.

The initiative involves 15 US transplant centers. So far, one recipient-donor pair has enrolled in the program. The pilot program has three main goals: increase access to living donor transplants; increase access to transplants earlier, when recipients are in better health; and work out how to create and sustain a national program.

What Is Paired Donation?

In 2020, 1095 people died while waiting for a liver transplant, according to a report from the Organ Procurement and Transplant Network (OPTN) — a public-private partnership that includes more than 250 transplant centers and 50 organ procurement organizations across the country.

Most liver transplants involve deceased donors. One way to improve access to lifesaving transplants is through living donation, by which a healthy individual donates part of their liver. Someone can participate in nondirected or "altruistic" donation, in which someone donates a liver to someone they don't know, or they can donate to a specific individual (usually a blood relative or a spouse).

With living liver donation, someone may receive a liver earlier, before they get sick enough to be given priority on the wait-list for deceased donation. Because the recipient is in better health, they also may have an easier time recovering from the surgery, Ruthanne Leishman, who manages paired donation programs at UNOS, told Medscape.

In some cases, an individual will want to donate an organ to a specific person, but testing reveals they would not be a good match. Paired donation allows incompatible donors and recipients to find matches with other incompatible pairs. Each donor matches with the other pairs' recipient, so the organs are essentially swapped or exchanged between the two pairs.

"People who want to donate get excited about the fact that they are not just helping their loved one but they're also helping somebody else," Leishman said.

Paired kidney donation programs have been running since 2002, but paired liver donation is relatively new. Since the first US living-donor liver transplant in 1989, the procedure has become safer and is a viable alternative to deceased liver donation. A growing number of living donor programs are popping up at transplant centers across the country.

Still, living-donor liver donation makes up a small percentage of the liver transplants that are performed every year. In 2022, 603 living-donor liver transplants were performed in the United States, compared to 8925 liver transplants from deceased donors, according to OPTN data. Samstein estimates a couple dozen paired liver exchanges may have been performed in the United States over the past few years within individual hospital systems. A goal of this pilot program, along with increasing access to liver transplants, is to see whether paired liver donation works on a national level, Leishman said.

Challenges to Building a National Program

There are several notable differences between living donor kidney transplants and living donor liver transplants. For example, living donor liver transplant is a more complicated surgery and poses greater risk to the donor. According to the OPTN 2020 Annual Report, from 2015–2019, the rehospitalization rate for living liver donors was twice that of living kidney donors up to 6 weeks after transplant (4.7% vs 2.4%). One year post transplant, the cumulative rehospitalization rate was 11.0% for living liver donors and 4.8% for living kidney donors.

The risk of dying because of living donation is also higher for liver donors compared to kidney donors. The National Kidney Association states that the odds of dying during kidney donation are about 3 in 100,000, while estimates for risk of death for living liver donors range from 1 in 500 to 1 in 1000. But some of these estimates are from 10 or more years ago, and outcomes have likely improved, said Whitney Jackson, MD, the medical director of living donor liver transplant at UCHealth University of Colorado Hospital, Aurora, Colorado. Her program is participating in the UNOS pilot.

More recent data from OPTN provides some idea of risk: of 3967 liver donors who donated between March 1, 2008, to September 30, 2022, three deaths were reported within 30 days after transplant. However, the causes of death were not specified and therefore may be unrelated to the surgery. By comparison, of 74,555 kidney donors during that date range, 10 deaths were reported at 30 days post surgery.

In addition to a more complex surgery, surgeons also have a smaller time window in which to transplant a liver than than they do to transplant a kidney. A kidney can remain viable in cold storage for 24–36 hours, and it can be transported via commercial airlines cross country. Livers have to be transplanted within 8–12 hours, according to the OPTN website. For living donation, the graft needs to be transplanted within about 4 hours, Samstein noted; this poses a logistical challenge for a national organ paired donation program.

"We worked around that with the idea that we would move the donor rather than the organ," he said. The program will require a donor (and a support person) to travel to the recipient's transplant center where the surgery will be performed. While 3 of the 15 pilot paired donation transplant centers are in New York City, the other programs are scattered across the country, meaning a donor may have to fly to a different city to undergo surgery.

Including the preoperative evaluation, meeting the surgical team, the surgery itself, and follow-up, the donor could stay for about a month. The program offers up to $10,000 of financial assistance for travel expenses (for both the donor and support person), as well as lost wages and dependent care (for the donor only). Health insurance coverage will also be provided by the pilot program, in partnership with the American Foundation for Donation and Transplant.

The program requires that transplant candidates (the recipients) be at least 12 years old, be on the waiting list for deceased liver donation at one of the pilot's transplant centers, and have a Model for End-Stage Liver Disease (MELD) score of 25 or less. All potential donors must be 18 years or older and must undergo a medical and psychosocial evaluation. Nondirected donors can register with the program, and they will be paired with a candidate on the liver transplant waiting list at the same transplant center.

The 1-year pilot program is set to begin when the program conducts its first match run — an algorithm will help match pairs who are enrolled in the program. About five to seven enrolled pairs would be ideal for the first match run, a UNOS spokesperson said. It is possible that the 1-year pilot program could run without performing any paired transplants, but that's unlikely if multiple pairs are enrolled in the system, the spokesperson said. At the time of this story's publication, the one enrolled pair are a mother and daughter who are registered at the UCHealth Transplant Center in Colorado.

Is a National Liver Paired Donor Program Feasible?

While the UNOS pilot program offers financial assistance for expenses related to liver donation, some transplant surgeons are skeptical about the potential travel component of the pilot program.

The pilot program requires that the donor bring one support person with them if they need to travel for the surgery, but undergoing major abdominal surgery from a transplant team they are not familiar with may be stressful, said Peter Abt, MD, a transplant surgeon at the Hospital of the University of Pennsylvania and the Children's Hospital of Philadelphia. "That's a big ask," he said, "and I'm not sure many potential donors would be up to that."

John Roberts, MD, a transplant surgeon at the University of California, San Francisco, agreed that the travel component may put additional stress on the donor, but "if it's the only way for the recipient to get a transplant, then the donor might be motivated," he added.

Jackson remains optimistic. "Our experience so far has been that, yes, some people have been hesitant for things like traveling, but a lot of people who seem to be genuinely dedicated to the idea of living donation have been very enthusiastic," she noted.

Leishman agreed that the travel aspect appears to one of the greatest barriers to participants entering the program but noted that a goal of the pilot program is to understand better what works — and what doesn't — when considering a liver paired donation program on a national scale. "[Our] steering committee has put together a really nice framework that they think will work, but they know it's not perfect. We're going to have to tweak it along the way," she said.

More information on the UNOS paired liver donation pilot program can be found on their website.

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