Incremental impact of organ allocation changes and machine perfusion technology on liver transplant waitlist and volumes

The waitlist for liver transplants continues to grow due to a better understanding of the lifesaving role of liver transplantation in patients with end-stage liver disease. To facilitate access to transplants for these patients, there has been continued interest in changing allocation criteria and exploring more medically high-risk organs and donors. In addition, updated metrics such as waitlist mortality help us set benchmarks for the quality of care provided to patients with end-stage liver disease. Since 2002, the allocation of livers has been based on the MELD score, which is able to predict the medical urgency of liver transplantation. Over the years, several adjustments have been made to not only the score (eg, MELD-Na), but also the way organs are shared/allocated. In 2013, the Regional Share 35/National Share 15 policy was enacted, where patients with a MELD score >35 were given priority allocation in the regional donor service area. More recently, due to concern for geographic discrepancy, acuity circles (150, 250, and 500 nm) have been implemented. Preliminary investigations regarding the use of acuity circles demonstrated better access to organs for patients with MELD >29 and a higher allocation rate of organs from donation after cardiac death (DCD), especially in those with MELD exception scores.1 These changes have led to some unintended consequences.2 In the process of making organ access more equitable between “organ rich” and “organ poor” areas, these policies have led to increased logistical and likely financial challenges related to organ transport.3,4 In general, wait times have decreased for higher MELD patients while increasing wait times for lower MELD patients. The socioeconomic impact of these changes affecting lower MELD patients is unknown. Any strategy that results in increased waitlist time is likely to be associated with not only higher waitlist-related costs but could potentially increase the disparity in those patients who have reduced access to transplant centers/care.3 Besides transplant centers, organ procurement organizations have been under increasing pressure to improve “performance.” As a result of presidential executive orders and changes in the Centers for Medicare and Medicaid Services (CMS) Final Rule to update donation and transplant rates, organ procurement organizations are pursuing higher medical risk patients and organs. To improve the transplant rate, transplant centers are adapting by either changing practices regarding recipient listing or organ acceptance. There has been increased use of DCD and other medically higher-risk organs to provide access to the lower MELD patients on the list who are disadvantaged by the current system. When it comes to using higher-risk organs, machine perfusion appears to be paradigm-changing. While there are distinct advantages to both normothermic and hypothermic machine perfusion in terms of improving patient outcomes, the benefits of facilitating transplant logistics using distant organs or the use of higher donor risk index organs need to be emphasized.5 Mergental et al6 demonstrated that several livers that are being discarded in the United Kingdom, even late in the transplant process, could be successfully “rescued” and transplanted using normothermic machine perfusion (NMP). A study published by Brüggenwirth et al7 from 12 European transplant centers demonstrated that hypothermic machine perfusion was used to extend the duration of liver preservation to facilitate issues related to the timing of recipient operation. This was predominantly done due to a lack of available operating rooms. The present study by Wehrle et al8 describes the programmatic impacts of these changes in a highly experienced multicenter enterprise (belonging to the same parent organization) during the transition to acuity circles and the implementation of NMP. They found a significant reduction in median waitlist time from 79 days in the pre-acuity circle era to 49 days in the acuity circle era and 14 days in the NMP era. They also found a significant increase in the donor risk index in the NMP era. There was an increase in the transplant rate over the years at their transplant centers. Ultimately, this resulted in reduced waitlist mortality, increased access to transplants, and reduced waitlist-associated costs. The findings in the manuscript give us insight into the workings and adaptability of highly functional transplant centers. As the landscape of organ transplantation continues to change, transplant centers have dynamically responded to changing behavior and practices.9 Since 2013, there has been a steady increase in transplant volume year over year across the United States. These strategies include changes in organ acceptance practice, such as accepting more DCDs or steatotic grafts. For example, the authors state that in the pre-NMP era, the transplant center was accepting DCDs in donors up to 60 years old with no steatosis but now have expanded that to 70 years of age with up to 30% steatosis. In addition, they are accepting brain-dead donors with up to 50% steatosis.8 Looking at trends in DCD organ use, the year-over-year increase in DCD organs across the United States represents the largest percentage of increase in organ yield (Figure 1).FIGURE 1: Increasing number of brain-dead donations, DCD, and living donor liver transplantation (Source: OPTN).10 Abbreviation: DCD, donation after cardiac death.Centers are also making changes to recipient selection and listing strategy. Like the authors, there has been a tendency to seek out and list higher MELD patients (seen as increasing listing MELD over the eras) (Figure 2). Several more patients are being removed from the list without a transplant. In the study by Wehrle et al,8 there were 18 in the acuity circle era, 22 in the NMP era, and only 5 in the pre-acuity circle. The authors don’t comment on this, but based on our experience, we postulate that this behavior is likely a combination of better management of patients with cirrhosis and HCC (decrease in HCC-related listing), understanding the realistic probability of getting a transplant, and waitlist mortality being evaluated as a metric of transplant center performance.FIGURE 2: Number of patients added to the liver transplant waitlist stratified by listing MELD (Source: OPTN).10 Abbreviation: PELD, pediatric end-stage liver disease score.A third aspect of improving access to transplant includes not just increasing deceased organ use, but also finding other avenues to organ availability. There has been a steady increase in living donor liver transplantation in the United States (Figure 1). In the current study, this contributed to 14% of transplanted organs, especially in the acuity circle era.8 Not diminishing the role of NMP as being a key driver of change, but changes made due to the implementation of acuity circles and the continuous evolution of practices across the years from transplant centers have led to success. There have been programmatic improvements in overall waitlist survival in both the acuity circle and the NMP era. Hence, the authors believe that NMP has synergistically contributed to changes made to the program in the acuity circle era by facilitating the use of higher-risk organs with acceptable posttransplant outcomes. Although in the presented data 6-month outcomes/survival is similar in the NMP era with likely higher DRI grafts, longer term outcomes are yet to be determined. Other complications, such as cholangiopathy, are not presented in this study. As we continue to explore how machine perfusion will affect organ availability and acceptance, there are some challenges that will determine widespread applicability. Except for 2 Federal Drug Administration (FDA)-approved NMP devices, hypothermic machine perfusion remains under investigation. Normothermic regional perfusion, which has been used outside the United States, is slowly coming into practice in the United States.5 The cost of these technologies, including the cost of “dry runs” (that don’t yield in a transplant), is likely to impact how they will be used by programs across the country. Health care expenditure and reimbursement are highly complex in the United States. There are likely some monetary benefits of NMP when looking at it from a “whole cost” perspective, which includes the patient journey from waitlist to after transplant. Hence, it is key that health care systems, insurance companies, and CMS come to the table to discuss these financial implications. The vision of the US transplant system is to provide lifesaving transplants to everyone in need. The authors of this manuscript and their transplant centers should be commended for striving to achieve this goal. High-performing transplant centers and organ procurement organizations will continue to evolve and address the need to provide equitable access to liver transplants for all patients. On a national scale, the ratio of number of transplants to waitlist additions has been increasing every year, suggesting that we are slowly bridging the gap of an expanding waitlist (Figure 3). We are in an exciting era of incorporating rapidly emerging technological advances into transplantation that will ultimately increase organ utilization and decrease the burden of end-stage liver disease.FIGURE 3: Ratio of the number of liver transplants to the number of waitlist additions each year (source: OPTN).10