Advancing the Field of Pediatric Liver Transplantation: Urgent Action Items Identified During the 2022 Society of Pediatric Liver Transplantation Meeting

The Society of Pediatric Liver Transplantation (SPLIT) has grown into a community of over 40 centers with synergistic platforms in research, education, advocacy, quality improvement, and clinical care. In 2019, SPLIT joined forces with the Transplantation Society in a mission to improve the lives of children who require (and undergo) liver transplantation (LT). The 2022 SPLIT Annual Meeting highlighted a keynote address discussing the persistent problem of 5% pediatric waitlist mortality.1 This brief report proposes 3 urgent actionable items toward ensuring that all children in need have access to LT. ACTION ITEM 1: PEDIATRIC LIVER TRANSPLANT SURGEONS SHOULD ALL BE TRAINED TO PERFORM TECHNICAL VARIANT GRAFTS Pediatric LT surgeons should have the skills necessary to care for all LT candidates. Infant candidates have the highest waitlist mortality partly due to poor access to size appropriate deceased whole organs.1 Use of technical variant grafts (TVGs), including living donor (LD) grafts and split deceased grafts, is a way to increase the pool of available organs. Despite emerging data that TVGs result in superior outcomes and a 63% mortality reduction compared with whole organs, TVGs continue to be underutilized.2,3 In the United States, only 6.3% of deceased liver donors meet United Network for Organ Sharing criteria for split LT (SLT) and only 3.8% are utilized for SLT, a stark contrast from other countries with mandatory SLT policies.4,5 Discussion at the 2022 SPLIT meeting identified several barriers to TVG practice adoption: (1) not all surgeons possess the surgical experience/expertise; (2) not all transplant programs are adequately staffed or experienced in coordinating the logistics of TVG use; and (3) there is no concerted national strategy/policy governing TVG credentialing or minimum standards of care. To decrease morbidity and mortality on the pediatric waitlist, it is imperative that we increase utilization of TVGs. To do this, we must ensure that all future surgeons are comprehensively well trained in TVG practices. Potential options for increasing the number of surgeons and programs with LDLT and other TVG capabilities are illustrated in Figure 1.6FIGURE 1.: Potential pathways to increase number of surgeons and programs that can provide LDLT (living donor liver transplantation) and other TVGs (technical variant grafts).ACTION ITEM 2: EVERY CHILD DESERVES ACCESS TO AN LD TRANSPLANT PROGRAM LDLT is one way to expand the pool of size-matched grafts, reduce children’s wait time for transplant, and improve outcomes.7,8 Pediatric LD recipients have better graft and patient survival than deceased donor recipients.1 However, from 2018 to 2020, only 13% of US pediatric LTs were LDLTs; this percentage has remained stagnant over the past decade.1 LDLT is unfortunately utilized at only a minority of pediatric LT centers. Between 2009 and 2019, only 50% (44 of 88) of pediatric LT centers performed an LDLT, and only 13 centers performed 5 or more LDLTs in any given year.7 High LDLT center volume is not only protective against waitlist death; it also increases a child’s chance at prompt LT—before they deteriorate and accumulate morbidity.7,9 Even when a child has no identified LD, listing at an LDLT center may provide access to a nondirected LD. Allocation protocols for nondirected LD grafts often prioritize pediatric recipients.10 To mitigate social, economic, and geographic disparities in access to LDLT, we must ensure that every child has access to LDLT. This should include requiring formal discussion about LDLT as part of every pediatric LT evaluation. If the home center does not perform LDLT, the LDLT discussion should be conducted by a consulting physician from an LDLT center, potentially via telehealth. Additionally, centers who do not perform LDLT should provide specific contact information for an LDLT center and assistance with arranging a multicenter evaluation. Given that LDLT requires surgical expertise and experience, we recommend developing specific criteria for pediatric LDLT centers that consider experience with donor evaluation, family preparation, and surgical and postoperative management. Non-LDLT centers could partner with specialized LDLT centers, so that pre- and posttransplant care can be provided locally while still ensuring access to LDLT. ACTION ITEM 3: REMOVE PATIENTS WITH NEONATAL ACUTE LIVER FAILURE AND PRIMARY UNRESECTABLE HEPATIC MALIGNANCIES FROM A CENTER’S REPORTED SCIENTIFIC REGISTRY OF TRANSPLANT RECIPIENTS OUTCOMES The distinct diseases, physiological responses, and neurodevelopmental aspects of LT in the pediatric population have resulted in published guidelines regarding the evaluation of children for LT.11 And yet, the decision to list a patient for LT ultimately resides with individual centers. At times, there may be conflict between what is right for the patient versus what is right for the center’s outcome data, particularly for children with transplant indications that may be associated with lower LT survival outcomes. Unlike in adult LT wherein any given center may perform hundreds of LTs a year, even the largest pediatric LT centers only perform 30–40 LTs a year. With such small LT numbers, 1 or 2 patient/graft losses can significantly impact a center’s scientific registry of transplant recipients (SRTR) outcome data and ultimately result in a center coming under review. As a result, centers must make difficult decisions about how many high-risk cases to take on: an ethical conundrum that no center should face. Neonatal acute liver failure (NALF) and primary unresectable hepatic malignancies are 2 disease processes in which LT survival may be lower than average. However, LT may be only chance for long-term survival. For infants weighing <6 kg with NALF, there is a higher incidence of complications, a prolonged need for intensive care, and lower patient and graft survival.12 For children with primary hepatic malignancies (a group with rising incidence), although LT survival has improved over time, outcomes remain less than that achieved for nontumor patients.13,14 Sadly, cancer can recur independent of graft health. Although LT survival outcomes for these 2 groups might be lower than average, we must put this into the context that mortality without LT is near 100% for these children. Unfortunately, a misguided emphasis on success metrics that are overemphasized by regulatory agencies and payors results in instances in which centers may defer offering lifesaving LT. Thus, there are children who would have survived, and thrived, that were never given the opportunity. This is an unacceptable reality. Separating outcome data for NALF and primary hepatic malignancies from SRTR reporting would enable centers to give these children their only chance at long-term survival. At a minimum, patients with primary hepatic malignancies enrolled in trials studying the role of LT when tumors are unresectable should be excluded from SRTR center data. In the long run these studies will determine how to best utilize LT for this population of children. CONCLUSIONS AND FUTURE DIRECTIONS Although survival after pediatric LT is excellent, children who could be saved by LT continue to die on the waitlist or are never offered LT. We cannot feel satisfied until we achieve zero waitlist mortality. Every child, regardless of their location, should have the opportunity to receive LT in the timeliest manner possible by utilizing LDLT and deceased TVG options. Additionally, we as a transplant community should strive to take risks on children for whom LT could be lifesaving, even if their outcome is not guaranteed. Centers that feel comfortable transplanting children with NALF and primary hepatic malignancies should be encouraged to do so when clinically appropriate, without fear of repercussions for individual center data. We call on regulatory bodies (including United Network for Organ Sharing), as well as individual transplant providers, to make systemic changes and personal commitment to implementing these necessary changes.

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