Expanding pediatric liver transplants: the role of split grafts, allocation policies, and machine perfusion

Abstract

Purpose of review

Pediatric liver transplant waitlist mortality remains disproportionately high, particularly among infants under one year old. Despite the success of split liver transplantation (SLT) in improving pediatric access to transplants, its utilization remains limited. This review examines barriers to SLT adoption, explores the impact of pediatric-focused allocation policies, and evaluates the potential of machine perfusion technology in expanding the pediatric donor pool.

Recent findings

Studies have demonstrated that SLT outcomes are comparable to whole graft transplants when performed at experienced centers. However, logistical challenges, technical expertise, and policy limitations hinder its widespread adoption. Countries with pediatric-prioritized allocation and mandatory SLT policies, such as Italy and the United Kingdom, have significantly reduced pediatric waitlist mortality. Additionally, machine perfusion technology has emerged as a promising solution, allowing for ex vivo graft splitting and reducing ischemic injury, which may enhance graft utilization.

Summary

A multifaceted approach is necessary to improve pediatric liver transplant outcomes, including stronger pediatric-first allocation policies, SLT training expansion, and integration of machine perfusion technologies. Implementing these strategies in the United States could significantly reduce pediatric waitlist mortality without negatively impacting adult transplant candidates.

INTRODUCTION

The field of transplantation is experiencing an exciting period of innovation. Last year, the first successful gene-edited kidney xenotransplantation was performed, followed by the recent FDA approval of two companies to conduct clinical trials using genetically modified pig kidneys [1,2]. Machine perfusion technology has also gained significant prominence in 2024, contributing to a 23.5% increase in donation-after-circulatory-death (DCD) donors compared to 2023 [3]. Additionally, the evolving definition of transplant oncology now extends beyond primary liver tumors [4]. Meanwhile, the liver allocation policy using MELD 3.0 was implemented for the first time to address gender disparities in transplant access [5]. 

Box 1.

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Despite these advances, progress in pediatric liver transplantation has stagnated in recent years. With birth rates remaining stable, the annual number of pediatric liver transplants in the United States has remained relatively constant [6]. However, pediatric waitlist mortality remains a significant concern, particularly for candidates under 1 year old, whose waitlist mortality rate is close to three times higher than that of all pediatric candidates and approximately 50% higher than that of adults [6] (Fig. 1). This article examines the underlying causes of this disparity and explores potential strategies to reduce pediatric waitlist mortality.

FIGURE 1.

Liver candidate pretransplant mortality. Data sourced from OPTN/SRTR 2023 Annual Data Report [6].

THE ROLE OF TECHNICAL VARIANT GRAFTS IN REDUCING PEDIATRIC WAITLIST MORTALITY

The annual volume of pediatric liver transplants in the United States has remained stable, around 540 cases per year [6]. As congenital diseases are the leading indication for transplantation, the median recipient age at the time of transplant has remained unchanged, approximately 2 years old [7]. As in the adult liver transplantation community, whole grafts have been the primary graft used due to the relative abundance of deceased donors compared to living donors in pediatrics as well. However, the continued reliance on whole liver graft availability for pediatric recipients remains a major barrier to timely transplantation, as the availability of size-appropriate whole livers is severely limited. In 2024, only 40 livers from deceased donors under 1 year old and 109 from donors between one and five years old were recovered, while 216 and 219 candidates, respectively, were added to the waiting list during the same year, highlighting a severe mismatch between demand and availability of size-appropriate livers [8].

Split liver transplantation (SLT), a type of technical variant graft, has proven to be an effective strategy for expanding the donor pool by dividing a single liver into two viable grafts, benefiting both pediatric and small adult recipients, who are also disadvantaged by their smaller body size [9]. Interestingly, early outcomes of in-situ split liver procurement in the United States were largely unfavorable due to a steep learning curve and limited technical expertise [10–14]. Additionally, in its early years, prolonged surgical times and increased blood loss, often necessitating blood transfusions, raised concerns about potential impairment to other abdominal and thoracic organs [15]. Despite these early challenges, recent studies indicate that outcomes of technical variant grafts, including split grafts, are no longer inferior to whole grafts, particularly when performed at high-volume centers [16^▪▪,17,18]. Furthermore, Mazariegos et al. demonstrated that greater utilization of technical variant grafts (TVGs) at pediatric liver transplant centers is associated with shorter waitlist times and lower waitlist mortality [19^▪▪]. From a different perspective, Kwon et al., using an intention-to-treat analysis, highlighted that the timing of transplantation, rather than graft type, is the most critical factor for a pediatric candidate's long-term survival once listed [20^▪▪].

Despite the first reported case of in-situ split graft procurement in the U.S. in 1997, nearly three decades ago, its utilization has remained limited, with SLT expertise concentrated in only about 10 pediatric transplant centers [21,22]. Currently, SLT accounts for less than 20% of pediatric liver transplants, contributing approximately 100 cases annually [6] (Fig. 2). The combination of a low annual case volume and the concentration of SLT procedures in a few specialized centers has made it challenging for the broader pediatric transplant community to gain practical experience. Beyond the limited surgical exposures, logistical barriers further hinder the widespread adoption of split liver procurement. The unpredictable timing of donor availability requires urgent coordination of an experienced hepatobiliary surgical team to travel to the procuring hospital on a short notice. The procurement operating room is not an optimal setting to perform a complex hepatectomy. Unlike living donor liver hepatectomy, detailed preoperative imaging is not typically available. Furthermore, the dynamic nature of donor hemodynamics and the simultaneous presence of multiple organ procurement teams introduce additional challenges, necessitating a swift yet precise split procedure to minimize blood loss and optimize graft quality.

FIGURE 2.

Split or partial liver transplants in children. Data sourced from OPTN/SRTR 2023 Annual Data Report [6].

Studies have also shown that the use of living donor grafts, another form of TVG, is associated with lower waitlist mortality [19^▪▪,23–25]. However, its current usage is also concentrated at only a few pediatric centers [19^▪▪]. Although the surgical principles of in-situ deceased donor split liver procurement closely resemble those of living donor left lateral hepatectomy, the stakes are significantly higher in the latter, as a healthy donor undergoes a major medically unnecessary surgery. Given these high stakes and cultural reluctance toward living donation in the U.S., expanding the use of split liver procurement, leveraging the virtually unlimited pool of deceased donor whole livers to meet pediatric demand, represents a more practical and impactful strategy for reducing pediatric waitlist mortality. It has been estimated that approximately 20% of all deceased donors meet the United Network for Organ Sharing (UNOS) guidelines for split liver utilization (age <40 years, use of a single vasopressor or less, transaminase levels no greater than three times the normal limit, and a body mass index of 28 or less), and a total of 11 529 deceased adult donor livers were procured in 2024 alone [8,26].

THE IMPACT OF PEDIATRIC-FRIENDLY LIVER ALLOCATION POLICIES

While expanding split liver transplantation is essential, its overall impact will be limited without complementary allocation policies. Global experience has demonstrated that pediatric-focused allocation policies, including prioritizing pediatric recipients and promoting split graft utilization, can significantly improve waitlist outcomes [27,28^▪▪].

In the United States, the first pediatric-focused allocation policy was implemented in 2000, prioritizing geographically available pediatric organ offers for medically urgent pediatric recipients [29]. However, despite this change, a significant proportion of pediatric grafts continued to be allocated to adult recipients, leading to no substantial improvement in pediatric waitlist mortality [30]. This prompted a policy revision in February 2020, mandating that all pediatric grafts be offered to pediatric recipients nationwide before being considered for adult candidates [29]. In July 2023, the updated Pediatric End-Stage Liver Disease (PELD) score, known as PELD-Cr, was introduced [31]. This revision incorporated serum creatinine levels, treated age and growth as continuous variables, and an age-adjusted mortality risk factor to better capture disease severity and reduce waitlist mortality. Additionally, in 2017, the Organ Procurement and Transplantation Network (OPTN) introduced a policy specifically identifying potential split liver donors; however, its impact has been minimal, as it serves as a guideline rather than an enforceable mandate [32].

Several other countries have adopted pediatric-focused policies that more aggressively promote split liver transplantation and prioritize pediatric recipients to a greater extent than the U.S., with notable success [27,28^▪▪]. In Italy, all deceased donors aged 18–50 years who meet standard risk criteria are mandatorily offered to pediatric transplant centers first as split liver grafts, unless there is a nationwide Status 1 recipient or a macro-area adult recipient with a MELD score ≥30 [33]. As a result, Angelico et al. demonstrated that the mandatory split liver policy increased SLT utilization from 49.3% to 65.8%, reduced the median waitlist time from 229 to 80 days, and decreased waitlist mortality from 4.5% to 2.5% [33]. Similarly, in 2005, the United Kingdom adopted the “Intention to Split” policy, mandating all eligible deceased donor livers meeting certain criteria (<40 years, ≥50 kg, ICU ≤5 days, stable hemodynamics) be considered for split liver transplantation, prioritizing pediatric recipients [34]. This led to a significant rise in SLT and the achievement of zero pediatric waitlist deaths for four years following its implementation [34].

In the United States, implementing stricter pediatric-friendly allocation policies and prioritizing, or even mandating, split liver procurement has significant potential to improve pediatric waitlist outcomes, as demonstrated by other countries. Importantly, these policies have not been shown to negatively impact adult liver transplant candidates on the waiting list [34,35]. Pediatric liver transplants accounted for only 5% of all liver transplants in 2024, representing a small fraction of total cases in the United States [8]. Given this, along with evidence from other countries, a stronger pediatric-friendly allocation policy is unlikely to disadvantage adult waitlist recipients while offering a significant opportunity to reduce pediatric waitlist mortality.

MACHINE PERFUSION AND THE FUTURE OF PEDIATRIC LIVER TRANSPLANTATION

Machine perfusion technologies have revolutionized adult liver transplantation. The use of DCD and steatotic liver grafts, once considered unsuitable for transplant, have significantly increased, and cold ischemic time is no longer a major limitation when grafts are preserved on a pulsatile perfusion pump [36]. While machine perfusion has profoundly transformed adult transplantation, its impact in pediatric liver transplantation remains limited. This is expected, as pediatric transplants prioritize optimal graft quality to ensure long-term survival and minimize complications. Although various machine perfusion technologies are currently not widely adopted for expanding marginal graft use in pediatric transplantation, they are increasingly being explored as a solution to the logistical challenges and graft utilization issues associated with split-liver procedures.

In 2020, an Italian surgical team reported the first case of a split-liver procedure performed while the liver was on hypothermic machine perfusion, successfully transplanting two recipients [37]. Their rationale for this approach was that the donor was unstable for in-situ split procurement, with a projected cold ischemic time exceeding 10 h. The following year, surgical teams from France and the Netherlands also reported additional split-liver procedures conducted while the graft was on hypothermic perfusion [38,39]. In 2023, an Australian surgical team published the first report of ex vivo split-liver procedures using a normothermic perfusion machine [40^▪]. Most recently, in 2024, an Austrian surgical group reported six cases in which right lobes were placed on a perfusion pump after the split procedure to optimize graft function. To the best of our knowledge, the first documented use of machine perfusion technology in the United States for a pediatric split recipient was reported by Gao et al., who described two cases in which whole adult liver grafts were initially placed on normothermic perfusion machines, followed by a back-table split before transplantation [41^▪].

Although in-situ splitting remains the ideal approach, providing two grafts at the donor hospital allowing for easier and fairer allocation and minimizing cold ischemic time, it is a labor-intensive procedure that poses significant logistical challenges, as previously mentioned. However, machine perfusion technology has the potential to overcome some of these obstacles, ultimately increasing the availability of partial grafts for pediatric recipients. By enabling a local procurement surgeon to retrieve the organ, rather than requiring an experienced hepatobiliary surgical team to travel to the donor hospital and perform the split procedure in a suboptimal environment, machine perfusion eliminates constraints related to donor location donor condition, procurement timing, and surgical environment. Additionally, performing the split procedure at the recipient center while the graft is being continuously perfused significantly reduces ischemic injury to both the left lateral segment and the remaining right lobe. The right lobe, which remains continuously perfused, can also be safely transported to distant locations if needed. Although no such clinical cases have yet been reported in the United States, integrating machine perfusion technology into the split-liver process could significantly expand the pediatric liver graft pool.

CONCLUSION

Despite advancements in transplantation, pediatric liver transplant waitlist mortality remains unacceptably high, largely due to the underutilization of technical variant grafts, particularly SLT. While SLT achieves outcomes comparable to whole grafts and reduces waitlist mortality, technical, logistical, and training challenges continue to limit its widespread adoption.

Addressing this disparity requires both policy reform and technological innovation. Countries with pediatric-prioritized allocation systems and mandatory SLT policies have significantly improved waitlist outcomes without compromising adult transplant candidates. The United States should adopt similar strategies, including stronger pediatric-first allocation policies, increased SLT incentives, and mandatory split liver procurement where feasible.

Finally, machine perfusion technology offers a promising solution to some of SLT's logistical challenges by enabling ex vivo graft splitting at the recipient hospital, optimizing graft preservation, and improving allocation flexibility. A comprehensive approach that addresses multiple facets, including SLT training, increased public awareness of current limitations, and the integration of machine perfusion, will be essential to ensuring timely and equitable liver transplantation for pediatric patients.

Acknowledgements

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Financial support and sponsorship

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Conflicts of interest

There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

• ▪ of special interest

• ▪▪ of outstanding interest