Eliminating Wait List Mortality: New Strategies for Organ Utilization in Liver Transplantation

Although outcomes after pediatric liver transplantation have improved substantially over the last several decades, making sure every child has access to life saving transplantation remains a key priority. Transplant programs across the country continue to pursue new strategies to expand organ availability and make better use of every liver that becomes available.

At UPMC Children's Hospital of Pittsburgh, use of living donor liver transplantation, split liver transplantation, broader utilization of deceased donor organs, and new approaches to organ preservation and assessment prior to transplant have allowed the program to nearly eliminate waitlist mortality. Finding ways to maximize the use of every organ that becomes available is of the highest priority.

Recent advances in organ preservation and perfusion technologies are providing transplant teams with additional opportunities to evaluate donor organs, extend preservation times, and support more complex utilization strategies, including split liver transplantation. These developments are happening along with efforts to expand the donor pool and increase access to transplantation for children.

George Mazariegos, MD, chief, Pediatric Transplantation at UPMC Children’s and director, Thomas E. Starzl Transplantation Institute, has helped lead many of these efforts at the national level. In the discussion below, Dr. Mazariegos shares his perspectives on the continuing challenge of pediatric waitlist mortality, the evolution of organ utilization strategies, and how advances in organ preservation may influence the future of pediatric liver transplantation.

Q: Even with advances in pediatric liver transplantation, some children in the U.S. continue to die while waiting for donor organs. How do you view the challenge of waitlist mortality?

A: Pediatric waitlist mortality remains a reality in the United States, but I view it as a fixable problem. I believe we have the tools and strategies to continue reducing that number and ultimately eliminate it nationwide, just as we have done here in Pittsburgh.

The challenge is not just in finding more donor organs. It is making sure we use every appropriate organ that becomes available. At UPMC Children's, we have focused on a comprehensive approach that includes living donor liver transplantation, increased use of deceased donor organs, and increased use of split liver transplantation.

Each of those strategies addresses a different aspect of the problem. Living donation creates an additional source of grafts. Split liver transplantation allows a single donor organ to benefit both a child and an adult recipient. Improved utilization of deceased donor organs helps ensure that potentially transplantable livers are not lost unnecessarily.

The common goal is to make certain that every graft is considered thoughtfully and used whenever it can be done safely and effectively. If we continue expanding those opportunities, I believe pediatric waitlist mortality can be brought close to zero.

Q: Why has organ preservation become such an important area of innovation in transplantation?

A: Since the beginning of transplantation, organ preservation has largely depended on static cold storage. The basic principle is straightforward: by cooling the organ, you reduce its metabolic activity and limit the ischemic injury that occurs while it is outside the body.

That approach has served transplantation extraordinarily well for decades, but it has always imposed a fixed preservation window. Once an organ is recovered, transplant teams are working against the clock. Hearts typically have only a few hours of preservation time. Livers have longer preservation times, but they are still constrained. Every aspect of transplantation, from transportation and recipient preparation to surgical planning is built around those limitations.

At the same time, the field has been trying to find ways to safely use organs that historically were viewed as higher risk. Donation after circulatory death organs are one example. These grafts undergo an additional ischemic insult before recovery and were often associated with greater concern regarding function and long-term outcomes.

Those two realities, the limitations of traditional preservation and the need to use more donor organs have driven many of the innovations we see today. New preservation technologies are giving transplant teams additional time, information, and flexibility in how donor organs are evaluated and used.

Q: How has the growing use of donation after circulatory death (DCD) organs changed the field?

A: DCD organs have been available since the early days of transplantation, but they were traditionally used much more cautiously. Because circulation has stopped before recovery, these organs experience an additional period of warm ischemia that can affect subsequent function. DCD livers were often considered extended-criteria organs and were generally used only in selected circumstances. Many transplant programs approached them with significant caution.

What has changed over the last several years is that preservation technologies have given us new ways to evaluate and support these grafts. That has contributed to a substantial increase in DCD liver utilization across the United States. Thousands of additional liver transplants are now being performed using organs that previously may not have been considered viable. For patients awaiting transplantation, that represents a meaningful expansion of the donor pool and an important opportunity to increase access to transplant care.

Q: Where do machine perfusion technologies fit into broader efforts to expand organ utilization?

A: The current technologies available in the United States fall into two general categories: normothermic machine perfusion, in which the organ is maintained at near-physiologic temperatures, and hypothermic oxygenated perfusion, in which the organ is preserved at much lower temperatures while continuing to receive oxygenation.

The common goal is to move beyond static preservation and create an environment that better supports the organ during the period between recovery and transplantation. With normothermic machine perfusion, the liver is functioning under near-normal physiologic conditions, allowing transplant teams to observe how the organ performs before implantation.

That is an important shift. Historically, decisions about donor organs relied heavily on donor characteristics, laboratory data, and visual assessment. Machine perfusion provides another layer of information by allowing clinicians to monitor the organ itself during preservation.

The technology also changes the logistics of transplantation. Rather than rushing to complete every step within the constraints imposed by static cold storage, transplant teams may have additional flexibility in how they evaluate organs and coordinate complex procedures. That additional time can be extremely valuable when making decisions about organ utilization.

The field is still determining where these technologies provide the greatest benefit and how different approaches compare with one another. Those questions will be answered through clinical experience and outcomes data. What is already clear is that machine perfusion has created opportunities that did not previously exist.

Q: One area you highlighted was split liver transplantation. How could machine perfusion help support that approach?

A: Split liver transplantation has always been one of the most effective ways to increase access to transplantation for children. When performed appropriately, a single donor liver can provide a graft for a pediatric recipient and a graft for an adult recipient. Few interventions have the potential to increase organ availability to that extent.

Despite its advantages, split liver transplantation has significant technical and logistical challenges. Splitting often occurs under circumstances that are far from ideal. The organ has been recovered at a distant hospital, transported under time constraints, and must be divided while everyone is working within a limited preservation window.

In many cases our expert surgical team has to perform the split procedure in the middle of the night under conditions dictated largely by time pressure rather than by what is most convenient or efficient for the surgical teams involved.

Machine perfusion creates the possibility of a different model. The liver can be returned to a center, placed on perfusion, monitored, and evaluated before a decision is made regarding splitting. The procedure can then potentially be performed in a more controlled setting with the appropriate personnel, equipment, and institutional support available.

Another important consideration is confidence in the organ itself. If the liver is being actively monitored during perfusion, teams may have greater assurance regarding graft function before proceeding with a split.

For pediatric transplantation, this is particularly important. Increasing the use of split liver transplantation is one of the most promising opportunities to expand access to donor organs for children. Technologies that make splitting more practical or reproducible could have a significant impact.

Q: UPMC Children's serves as the hub of a pediatric liver transplant network extending beyond Pittsburgh. How does that model help advance these efforts?

A: One of the unique aspects of our program is that the expertise developed at UPMC Children's is being applied across a broader regional network. In addition to Pittsburgh, we direct pediatric liver transplant programs at the University of Virginia, Atrium Health in Charlotte, NC; and AdventHealth in Orlando, FL.

The objective is straightforward: children receiving care at those institutions should have access to the same level of transplant expertise available at UPMC Children's.

That includes not only surgical expertise, but also the adoption of new technologies, new preservation strategies, and evolving approaches to donor utilization. As our experience grows, those lessons can be shared across all participating centers.

The network also provides an opportunity to evaluate innovations across different environments while maintaining a common clinical philosophy and standard of care. Our experience with machine perfusion, for example, extends across these sites rather than being limited to a single institution. Another way we disseminate best practice is by our leadership in the Starzl Network for Excellence in Pediatric Transplantation, a learning network launched by UPMC to bring together leading centers in the U.S. to work with urgency on solving the biggest challenges in pediatric transplantation- including eliminating wait list deaths.

Ultimately, the goal is to bring advanced pediatric transplant care closer to where patients live while maintaining the expertise and infrastructure necessary to support complex transplantation.

Q: What has been UPMC Children's experience with pediatric normothermic machine perfusion thus far?

A: We have now performed more than 20 pediatric liver transplant cases utilizing normothermic machine perfusion with pediatric donors. To our knowledge, this represents one of the larger experiences reported in pediatric transplantation.

An important aspect of this work has been demonstrating that these technologies can be applied in a pediatric setting, including in very small donors and recipients. Much of the early development of machine perfusion occurred in adult transplantation, so adapting these systems for pediatric use has required thoughtful implementation and experience.

Our experience has been sufficiently encouraging that we are currently preparing a manuscript that will summarize these cases and contribute to the growing pediatric literature on machine perfusion.

We are still early in the process, and many questions remain regarding optimal use, patient selection, and long-term outcomes. Nevertheless, the initial experience suggests that these technologies can be successfully integrated into pediatric liver transplantation and may provide important opportunities moving forward.

Q: Where is the field headed in terms of organ preservation, optimization, and expanding what may always be a finite pool of available organs?

A: Preservation is only the beginning of the story. One of the most exciting possibilities is the potential to use machine perfusion not simply to maintain organs, but to actively improve them before transplantation.

A great example is the challenge posed by steatotic livers. Many donor organs are currently underutilized because excessive fat accumulation raises concerns about function after transplantation. If machine perfusion can be used to allow clinicians to reduce that fat content or otherwise improve the condition of the organ, entirely new categories of donor livers may become available.

Beyond that, machine perfusion may provide a platform for delivering therapies directly to the organ outside the body. Because the liver is isolated within a controlled environment, it becomes possible to consider interventions that would be difficult to perform after transplantation.

Looking even further ahead, there may be opportunities to use these technologies in conjunction with gene-based therapies. One can envision modifying biologic pathways, addressing specific genetic defects, or reducing the likelihood of rejection before the organ is ever transplanted.

Many of these concepts remain investigational today, but they illustrate how quickly the field is evolving. What began as a preservation technology may ultimately become a platform for organ rehabilitation, organ optimization, and entirely new therapeutic approaches in transplantation.

Patient Referrals, Case Consultations, and Additional Information

To refer a patient to the Hillman Center for Pediatric Transplantation at UPMC Children’s Hospital of Pittsburgh for transplant evaluation, please send an email to PedsTXInquiry@chp.edu.