The current landscape of pediatric living donor liver transplantation in the United States: Benefits, challenges, and future directions.

Abstract

Liver transplantation is the gold-standard treatment for end-stage liver disease. The number of individuals in need of a liver transplant, however, has continued to exceed the number of donated liver grafts for transplantation. The challenge of matching the graft size to the generally small size of the pediatric recipient exacerbates the disparity. This is particularly true for infants younger than 1 year, who face the highest waiting list mortality rate.1 Living donor liver transplantation (LDLT), in which a portion of the liver of a healthy living adult is removed and transplanted into another adult or child, is one method to expand the donor pool. For pediatric recipients, the left lateral segment is most commonly used (Figure 1). Unlike in eastern countries, LDLT is performed relatively infrequently in the US and other western countries, with deceased donors making up most liver transplants performed. This article aims to review the current state of pediatric LDLT in the US by addressing its advantages, disadvantages, and potential for the future.FIGURE 1: Intraoperative images from a living donor left lateral segmentectomy. (A) Superficial cautery of the parenchyma demarcates the left lateral segment from the rest of the liver and is used to guide the plane of parenchymal transection. (B) Near completed parenchymal transection of the left lateral segment with exposure of the portal vein.Pediatric LDLT offers 2 substantial benefits: reduced waiting list mortality and superior post-transplant outcomes.2–5 The expansion in LDLT within our pediatric program effectively drove down the number of children on the waiting list despite the stable number of referrals and additions to the waiting list.6 As such, a higher volume of pediatric LDLT is associated with superior waiting list survival among centers in the US.7 A similar trend has been demonstrated in Europe, where a recent increase in the volume of pediatric LDLT was associated with a subsequent improvement in waiting list mortality.8 Although LDLT is one option to expand the donor pool for children, increasing evidence suggests that it may actually be the best option. Recent single-center, national, and meta-analyses have demonstrated superior graft and overall recipient survival with the living donor in comparison with deceased donor pediatric liver transplants.2–5 This survival advantage is likely multifactorial. Living donor grafts seem to be less prone to rejection.2,9 Furthermore, living donor transplantation provides the transplant team more control over the timing of the transplant in contrast to deceased donor pediatric liver transplant, and this semielective nature of the operation offers the opportunity to ensure that the recipient is medically optimized before transplantation. Lower rates of dialysis dependence, presence of ascites, and pretransplant intensive care unit hospitalization among pediatric living donor liver transplant recipients are objective reflections of this opportunity for medical optimization that likely contribute to superior survival outcomes.4,10 Lastly, another major advantage of LDLT is the availability of high-quality, detailed preoperative imaging. Pretransplant deceased donor imaging is dependent on the donor hospital imaging capabilities, which can vary in quality and is typically limited to computerized tomography that allows for crude assessment of graft size and vascular anatomy. In contrast, potential living donors at the University of Colorado undergo preoperative MRI in combination with CT with volumetric 3-dimensional reconstruction (Figure 2). This facilitates enhanced preoperative planning for anticipated vascular and biliary anomalies that may require reconstruction in the recipient. It also allows for superior graft-to-recipient size matching, which can further contribute to optimizing the recipient outcome.11,12FIGURE 2: Preoperative living donor liver MRI 3D reconstruction. (A) Detailed visualization of the portal vein (blue), hepatic artery (orange), and bile duct (green) anatomy. (B) Visualization of hepatic venous anatomy and the left lateral segment transection plane.Historically, the greatest limitation of LDLT has been a concern for donor safety and higher rates of vascular and biliary complications in the recipient when compared with deceased donor pediatric liver transplant. More recent reports demonstrate equivalent rates of such complications in addition to superior recipient survival.2,4–6,10,13 Donor safety is of the highest priority in any LDLT operation. The mortality and morbidity rates for living donor hepatectomy are 0.2% and 16%, respectively.14 An adult-to-child living donation has even safer outcomes, with donor mortality estimated to be between 0.09% and 0.2%. Therefore, although technical complications and donor safety may be perceived as the greatest challenges to pediatric LDLT, in reality, its greatest barrier is likely low utilization. Since 2002, LDLTs have only made up ~12% of all pediatric liver transplants in the US, ranging from 8% to 16% per year.3,15 Overall, the use of LDLT in the pediatric population has remained relatively stable, with perhaps a promising uptrend in utilization from a minimum percentage observed in 2013 to the highest percentage of pediatric LDLT observed to date, seen most recently in 2022 (Figure 3). Although this trend is encouraging, pediatric LDLT remains focused in a few select centers. Between 2009 and 2019, only half of the centers performing pediatric liver transplants performed even a single pediatric LDLT.7 Even among the centers that did perform at least 1 living donor transplant, the median number of pediatric liver transplants per center was fewer than one per year across that time span. Although center living donor transplant volume may impose a geographic limit on access to this life-saving transplant option, there is an additional racial and socioeconomic disparity in access to pediatric LDLT. African American candidates and candidates with public insurance were half as likely to undergo an LDLT in comparison with Caucasian candidates and candidates with private insurance, respectively.16FIGURE 3: Percent of pediatric liver transplants from living Donors in the US in the model for end-stage liver disease/pediatric end-stage liver disease era. Data were obtained from Organ Procurement and Transplantation Network.15Considering the waiting list and post-transplant survival advantages of LDLT and the disparities in access to this treatment option, future advances in pediatric LDLT must focus on expanding access to living donation. One such recent exciting advance in the field is nondirected living liver donation. Commonly also referred to as “altruistic” or “anonymous” living liver donation, nondirected donation involves a living donor who is willing to donate to a stranger on the waiting list. At least 46 pediatric LDLTs from nondirected donors have been reported in the US between 2014 and 2019 at 18 transplant centers.17 Although this is a small number at a national level, nondirected donors can have a significant impact on the pediatric waiting list at the few centers that have developed nondirected living liver donor programs. At our center, for example, we have observed an increasing trend in nondirected living liver donation, with nondirected donors making up approximately half of the pediatric LDLTs since we initiated the nondirected program in 2017 (Figure 4).6,15,18 In addition to expanding the pool of living liver donors, nondirected donation may also help address socioeconomic disparities in access to living donation, as nondirected donors can act as living donors to candidates who otherwise would not have a suitable directed living donor.17 Nondirected donation comes with unique challenges in regard to donor evaluation and allocation, for which recommendations from a North American collaboration have been recently released to help address.19 Ultimately, national policies are needed to expand both directed and nondirected living donation by eliminating disincentives to living donation (eg, financial costs) and increasing access to institutions that offer pediatric LDLT, either by expanding the number of institutions that can offer living donation or by facilitating multilisting at current high-volume pediatric LDLT centers. Another possible implication of expanded nonrelated living donation through greater nondirected donation is the effect on the rates of rejection with LDLT. Prior experiences reporting lower rejection rates with LDLT have come from cohorts predominantly composed of related living donors, with a protective effect seen with maternal donors in particular.2,9,20 In our experience, the incidence of acute rejection was similar with nondirected and related directed living donors (33% vs. 21%, p = 0.5).FIGURE 4: Impact of the nondirected living donor program on the pediatric liver transplant waiting list at Children’s Hospital Colorado. (A) A considerable decrease in the number of children waiting for a liver transplant was noticed after 2018 at our center, despite stable referrals and additions. (B) This corresponds to an expansion of the living donor liver transplant program, with a considerable contribution from nondirected living donors. *On January 1 of the corresponding year. Data were obtained from Organ Procurement & Transplantation Network15 and Scientific Registry of Transplant Recipients.18 Abbreviations: DDLT, deceased donor liver transplantation; LDLT, living donor liver transplantation.In conclusion, recent studies have demonstrated that living donor transplants achieve the best survival outcomes for pediatric recipients. Despite this, living donors account for only 12% of pediatric liver transplants in the US. Although there is an increasing uptrend in this number in recent years, pediatric LDLT is only being performed at a few select institutions, meaning many families in this country do not have access to this transplant option. Nondirected living liver donors have helped expand the benefit of living donation to children without suitable directed living donors, but still only account for a small number of pediatric liver transplants nationally. Living donation can help drive down waiting list mortality for children with end-stage liver disease, but national policies will be needed to help further expand access to living donation.