Research recently published in JAMA Surgery demonstrates that living-donor liver transplant (LDLT) recipients gain an additional 13 to 17 life-years following their surgery compared with patients who remain on the donor waitlist.
This research also pushes back against long-held standards that patients in need of a liver transplant should have a Model for End-stage Liver Disease incorporating sodium levels (MELD-Na) score of at least 15 to be considered for transplant. Researchers found that patients with MELD-Na scores as low as 11 had a 34% decrease in mortality compared with those who remained on the waitlist.
“The really staggering part of the study was that we determined that the survival benefit is not something that increased by several months or even a year or two. The benefit that the patient can expect to gain is 13 years or more,” says Elizabeth Pomfret, MD, PhD, chief of transplant surgery in the University of Colorado School of Medicine and the senior author of the study.
“For almost two decades, a MELD-Na score of 15 has been the break point for when the benefit outweighs the risk associated with liver transplantation,” she says. "As a result, in many transplant centers, a patient with a MELD-Na score of less than 15 with a suitable and willing living donor would be considered ‘too well’ to justify the risk associated with LDLT.”
Pomfret and her research partners analyzed data from almost 120,000 patients and found that with a score as low as 11, “patients not only derive benefit from LDLT, but big benefit, with more than a decade worth of life-years. This impacts the potential treatment options for hundreds and perhaps thousands of patients with end-stage liver disease since the majority of new candidates added to the waitlist are patients with a MELD score of less than 15.”
Understanding risk
This research was initially inspired by a seminal 2004 study, which found that liver transplant survival benefit at one year was concentrated among patients who were at higher risk for pre-transplant death and had higher MELD scores. The goal of the study was to establish the point at which the risks associated with transplant equal or outweigh the risks of remaining on the waitlist.
“I knew from my own experience and that of my colleagues, that this data still being used today was probably not accurate any longer,” Pomfret says. “There are plenty of patients that we see who have a MELD score of 15 or less who could benefit greatly from transplant but typically are not competitive for a liver from a deceased donor because their MELD score is too low. For example, someone with a low MELD score but who has a belly full of fluid that has to be drained every week is at a much higher risk of dying than a patient with the same MELD score who doesn’t have this complication.”
It was those scenarios – patients with “low” MELD-Na scores who nevertheless were at higher risk of dying – that prompted Pomfret and her research partners to propose repeating the 2004 study, “but let’s go one step further and ask, ‘What is the lowest MELD score where you gain the benefit from LDLT and how many life-years do you gain?’” Pomfret explains.
Pomfret and her research colleagues designed a retrospective, case-control study of 119,275 liver transplant candidates, using data from the Scientific Registry of Transplant Recipients (SRTR). Their objective was to assess the survival benefit, life-years saved, and the MELD-Na score at which that survival benefit was obtained for individuals who received a LDLT compared with that for individuals who remained on the waitlist.
Gaining 13 to 17 life-years
By analyzing patient data, researchers found that those with a MELD-Na score of 11 or higher who received a LDLT gained an additional 13 to 17 life-years, which is a measurement of the additional number of years a person lives as a result of medical treatment.
The research findings illuminate an ethical debate that has been wrestled with for several decades, related to MELD scores and who is “too well” to receive a liver transplant. Some clinicians and researchers have argued that giving a liver to someone with a MELD score of 11 is harming them more than leaving them alone, since the risk of dying as a result of complications from liver transplantation was higher than the person’s chances of dying waiting on the list.
In case of deceased-donor liver transplant (DDLT), the data from the 2004 study have been integrated into longstanding national organ allocation and distribution policy. In 2005, the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) adopted a policy of “Share-15,” in which livers obtained from deceased donors would first be offered to waitlist candidates with MELD scores of 15 or greater.
“Our research team has recently analyzed the SRTR database between 2012-2021 to determine life years saved by DDLT at each interval of MELD-Na score,” Pomfret explains. “Similar to the findings with LDLT, a significant survival advantage of DDLT at MELD-Na scores as low as 12 was found, with nine years or more of life-years saved after liver transplant. This data is in press in the American Journal of Transplantation and will likely open up a whole new discussion of whether the ‘Share 15’ policy should be revised.”
“An important tool in our toolbox”
These research outcomes published in JAMA Surgery contribute important information to help promote widespread acceptance of LDLT, which has been slow to grow in the United States and western Europe despite excellent outcomes.
“This is a really complex discussion because we’re talking about a scarce resource in terms of deceased donor organs and we don’t want to be putting a recipient or a donor through major surgery if there’s not going to be significant benefit,” Pomfret says. “LDLT benefits the entire waiting list in that a patient undergoing LDLT is removed from the wait list, thereby giving another patient a greater chance of matching with a deceased liver.”
Pomfret says that Western countries, including the United States, have been hesitant to accept LDLT as an option for patients, especially those with low MELD scores.
“The risk to any living donor is our paramount concern as transplant surgeons,” Pomfret explains. “A living donor is, by definition, a healthy person who does not need a major operation. Although living kidney and liver donation has become safer with experience and new techniques, the possible risk for a major complication including death can never be zero.”
She adds that “in the setting of LDLT, we may have allowed the pendulum to swing so far to the risk aversion side that we inadvertently deny patients with end-stage liver disease this option despite outstanding outcomes. I think the real importance of this paper is letting people know that not only is LDLT a reasonable thing to consider in low MELD score patients, but it is sorely under-utilized. We need to expand our patient population of who we would do a living donor transplant in, because we have more than a decade of good data to support this as an important tool in our toolbox.”
