The history of pediatric organ transplantation spans several decades, beginning in the 1950s. The first pediatric kidney transplant was performed on a 16-year-old male with traumatic kidney injury in Paris on December 23, 1952. Although the patient received a kidney from a living donor, he passed away 21 days post-surgery. The world’s first pediatric liver transplant was carried out in Denver, Colorado, on March 3, 1963, on a 3-year-old famale with biliary atresia, who died due to uncontrolled intraoperative bleeding. In 1964, a pediatric small bowel transplant was attempted in Boston, but the patient succumbed 12 hours after surgery. Similarly, a pediatric heart transplant was performed in New York on December 6, 1967, on a newborn with Epstein’s anomaly, but the patient died 6 hours later [1].

In these early years, transplant outcomes were unsatisfactory. However, the advent of immunosuppressive drugs, such as cyclosporine in the 1980s and tacrolimus in 1993, dramatically improved success rates, making transplantation a routine practice. Approximately 2,700 liver transplants, 1,300 kidney transplants, 700 heart transplants, 100 lung transplants, and 50 small intestine transplants are performed annually on children worldwide.

In Japan, organ transplantation faced significant delays due to controversies surrounding the determination of brain death and its suitability as a criterion for heart transplantation in 1968. It wasn’t until 1999, following a 30-year hiatus, that organ transplants resumed under legally recognized brain death criteria. The Brain Death Law was enacted on October 16, 1997, and revised on July 17, 2010, allowing for organ donation, including pediatric organ donation, with familial consent. Brain-dead organ donation from children began in April 2011, and pediatric organ transplant numbers have seen a modest increase since then. Selection criteria for pediatric recipients have been revised over time to better match pediatric donors to pediatric recipients (e.g., heart transplants since December 15, 2015; liver since January 1, 2018; kidneys since October 1, 2018; pancreas since February 3, 2020; lungs since June 24, 2020). Japan performs approximately 60 kidney, 100 liver, 10 heart, 5–10 lung, and 2–3 small intestine transplants annually in pediatric patients.

Living donor transplantation remains the predominant form of organ transplantation in Japan, often involving relatives donating part of their organs to save the life of a loved one suffering from organ failure. While this approach is viable for patients requiring liver, kidney, or small bowel transplants, children who require heart or multiple organ transplants face extreme challenges, given the scarcity of organs donated by brain-dead individuals. Additionally, despite utmost care, living donor surgeries are not without risk, and there have been rare but serious complications [2].

A unique characteristic of pediatric organ transplantation in Japan is its heavy reliance on living donor transplants, while brain-dead organ transplants are infrequent. To reduce the physical and psychological burden on patients and their families, medical professionals must strive to raise awareness of brain-dead organ donation rather than rely solely on the voluntary donation of organs by living relatives.

In 2019, the Pediatric Liver Transplantation Committee of the International Liver Transplantation Society conducted a global survey [3]. Responses from 157 pediatric transplant centers across participating countries revealed 2,615 pediatric liver transplants performed in 2019. Of these, 526 (20.1%) were conducted in Europe, 505 (19.3%) in North America, 231 (8.8%) in South America, 27 (1.0%) in Africa, and 1,326 (50.7%) in Asia, with half of the total cases occurring in Asia. Biliary atresia accounted for the majority of indications, representing 50% of cases, while 30% of recipients were under 1 year old at the time of transplantation.

Transplant indications varied by region. Familial intrahepatic cholestasis was common in the Middle East, Central Asia, and South Asia; Wilson’s disease was prevalent in Southwest Asia, and North America saw higher cases of α1 antitrypsin deficiency. Brain-dead liver transplants were more frequent in North America and Europe, whereas living donor transplants were predominant in Asia, the Middle East, and Africa. Economically, living donor liver transplantation (LDLT) is often more prevalent in countries with lower GDP per capita, as policy investment is less costly [4].

Due to the chronic shortage of brain-dead donors and the favorable outcomes of LDLTs, the demand for LDLT is increasing in Europe and the United States [5]. The International Liver Transplantation Society, the North American Pediatric Liver Transplant Society, and the Japanese Society for Liver Transplantation collaborate on short-term fellowship exchanges to share expertise in brain-dead and LDLT techniques.

The long-term outcomes of pediatric liver transplantation are excellent, with 65.8% and 79.6% 20-year survival rates reported in Europe, the U.S., and Japan, respectively [6,7]. To alleviate the ongoing donor shortage, various technological innovations have been introduced. Machine perfusion (MP), a device that continuously perfuses organs, is now used to preserve organs such as the heart, lungs, kidneys, liver, and pancreas. MP has been shown to reduce primary nonfunction and bile duct complications, improve fatty liver and overall liver function, and even enable split-liver transplantation without prolonging cold ischemia time [8,9].

Minimally invasive surgery (MIS) for living donors has gained traction, particularly in regions like the Arab-Asian countries [10,11]. Since 2013, MIS has expanded to include right lobe donor surgery, becoming a standard practice. Additionally, robotic surgery has been rapidly adopted in Taiwan, Saudi Arabia, Korea, India, and other countries since 2017 [12].

Sixty years after the first pediatric liver transplant, the primary challenges have shifted from improving short-term outcomes to enhancing long-term survival and quality of life. For pediatric liver transplant recipients, the long-term use of immunosuppressive drugs poses significant risks. Successful weaning from immunosuppression could mitigate these risks and improve the postoperative trajectory. Studies report that between 43%–60% of pediatric liver transplant patients (compared to 8%–33% of adults) can successfully wean from immunosuppressive drugs, especially in cases more than 2 years post-living donor transplant [13].

Graft fibrosis remains a persistent concern, with prevalence rates as high as 64% a decade post-transplantation [14]. This condition often progresses silently, without symptoms, and while fibrosis is frequently observed in biopsy reports, its impact on long-term outcomes requires further exploration [15]. In a series of 731 pediatric liver transplants performed at the National Center for Child Health and Development between 2005 and 2023, fibrosis was observed in 14.4% of cases. These were managed with increased immunosuppression, and long-term graft survival did not significantly differ between patients with or without fibrosis.

Another critical challenge is the transition of pediatric transplant patients to adult care facilities. Noncompliance with immunosuppressive regimens after transitioning to adult care accounts for 24.7% of patient deaths [16]. Individualized care strategies and multidisciplinary collaboration are crucial to ensuring these patients’ safe and supportive transition.

In Japan, the first LDLT was performed in November 1989 by Nagasue et al. [17] at Shimane University on a 1-year-old male with end-stage liver cirrhosis caused by biliary atresia. Since then, the number of liver transplants has steadily risen, reaching 11,693 procedures by the end of 2023. According to the Japanese Society for Liver Transplantation’s annual registry, 3,962 pediatric liver transplants (for patients under 18 years of age) had been carried out by the same time, with approximately 100 pediatric procedures being performed annually. The 10-year patient survival rate remains relatively consistent at 88.5% for brain-dead donor transplants and 86.3% for living donor transplants. Fig. 1 illustrates the annual trends in the number of liver transplant cases in Japan. While most liver transplants in the country involve a living donor providing a portion of their healthy liver, there has been a notable increase in the number of transplants from brain-dead donors in recent years.

Figure 1. The annual trends in the number of liver transplant cases in Japan. Ped, pediatric; LDLT, living donor liver transplantation; DDLT, deceased donor liver transplant.

Currently, there are 70 facilities in Japan that perform LDLTs, 21 of which are equipped to handle pediatric cases [18]. Additionally, 28 facilities perform brain-dead donor liver transplants, and 16 of these are able to carry out pediatric brain-dead donor transplants. Given the limited number of pediatric liver transplant cases—approximately 100 per year, including around 15 to 20 brain-dead donor cases—there is a clear need to both decentralize and centralize transplant services. For comparison, the United Kingdom, with half of Japan’s population, has only 7 liver transplant facilities, including those for both living donor and brain-dead donor procedures.

By consolidating pediatric liver transplant cases at specialized centers, we can develop a system that provides high-level care, prevents the dilution of human and financial resources, and creates an optimal environment for training the next generation of surgeons. While the declining birth rate continues to reduce the number of pediatric patients, the demand for high-quality care for individual children is growing. Because transplant recipients must take immunosuppressant medications for life, they require long-term, specialized care. Fortunately, pediatricians trained at the National Center for Child Health and Development are now practicing across the country, allowing patients who received transplants at our center to continue their follow-up care locally.

Moving forward, one of the critical challenges for our generation of supervising physicians will be striking a balance between decentralization and functional centralization, ensuring that high-quality pediatric transplant care is accessible to all patients while continuing to train young surgeons.

The National Center for Child Health and Development, established in 2001 as one of Japan’s leading specialized medical research institutions, initiated its pediatric liver transplant program in November 2005. Fig. 2 illustrates the number of liver transplant cases at the National Center for Child Health and Development. By the end of July 2024, the center had performed a total of 870 liver transplants. Since 2010, the annual number of cases has remained steady at around 60 to 70, with the center accounting for 60% to 70% of all pediatric liver transplant procedures in Japan. The 10-year patient survival rate at the center stands at 93%, which is favorable compared to the national average. Despite concerns that a declining birth rate would reduce the number of surgical procedures and liver transplants, the center has successfully centralized cases, largely due to strong transplant outcomes and effective dissemination of information through academic publications.

Figure 2. The number of organ transplant cases at the National Center for Child Health and Development. LDLT, living donor liver transplantation; DDLT, deceased donor liver transplant.

Pediatric transplant patients often face complex perioperative and surgical challenges, requiring lifelong immunosuppression and long-term follow-up. In Japan, living donor transplantation remains the primary modality, though it carries its own risks. For some pediatric patients, such as those requiring heart or multi-organ transplants, brain-dead organ donation is the only option. Thus, it is vital to raise public awareness about the importance of brain-dead organ donation to save more lives.

As the number of pediatric organ transplant cases grows, additional support—both human and financial—will be required to address the unique challenges these patients face as they transition to adulthood. Japan’s forthcoming “Administration for Children and Families,” set to launch in April 2023, offers hope that pediatric care, especially for those requiring transplantation, will receive greater attention from policymakers.

There was no funding related to this study.

All authors have no conflicts of interest to declare.

Conceptualization: MK, SS. Data curation: MK, SS, HO. Project administration: All. Supervision: HO. Writing – original draft: MK, SS. Writing – review & editing: MK, HO.