Objectives: Liver transplantation can be salvage or primary therapy for children with biliary atresia. In this study, we investigated the effects of sex, race, and donor type on outcomes.
Materials and Methods: We used the United Network for Organ Sharing database to perform a retrospective analysis of 1382 pediatric transplant recipients with biliary atresia, in which we compared sex, race, and donor type using standard statistical tests. We analyzed graft failure and mortality with Kaplan-Meier and Cox regression.
Results: No significant sex-based differences were found. Black (69.6%) and Hispanic (58.8%) recipients primarily relied on public insurance (P < .001). Com-pared with non-Hispanic White recipients, Black recipients had higher Pediatric End-Stage Liver Disease scores (17.8 vs 14.4; P < .001), used living donors less (16.9% vs 29.2%; P = .004), and relied more on nationally shared organs (33.1% vs 27.1%; P = .026). Among deceased donor transplant recipients, total preservation time was significantly shorter for Non-Hispanic White recipients compared with recipients of other races (P = .010). For living donor transplant recipients, Black race (hazard ratio 10.91; P = .009) and increasing donor age (hazard ratio 1.09; P = .048) were significant independent risk factors for graft failure.
Conclusions: Disparities in disease severity, insurance, donor access, and logistics are critical considerations for equitable management of biliary atresia.

Key words : Graft survival, Living donor, Patient survival, Racial disparities, Sex differences

Introduction

Approximately 1 in 8000 to 1 in 18 000 newborns worldwide are affected by biliary atresia (BA), the main reason for liver transplant in children.¹ Even with important advances in surgical methods and posttransplant management, BA still represents a large share of pediatric liver transplants in the United States. This highlights the importance of assessing equity in access and outcomes for this group.
Population-based data from the United States has consistently shown links between the incidence of BA and various demographic factors such as race, ethnicity, sex, and socioeconomic status. National and state registry analyses have found higher rates among females, non-Hispanic Black infants, and Asian or Pacific Islander populations compared with non-Hispanic White infants.^2-6
Despite advances in pediatric liver transplanta-tion, the field has evolved through several key surgical and technical milestones that have shaped current practice. Early experiences with pediatric liver transplant were limited by organ availability and technical challenges, particularly in small infants. The development of reduced-size, split, and segmental graft techniques has represented a major breakthrough, allowing expansion of the donor pool and improved access for pediatric recipients. Subsequently, living donor (LD) liver transplant has emerged as a critical strategy, especially in regions with limited deceased donor (DD) availability, enabling timely transplant and reduced waitlist mortality. Early reports of segmental and related LD liver transplant in pediatric patients have shown the feasibility and safety of these approaches and laid the foundation for their widespread adoption in modern practice.^7-9
In parallel, technical refinements, particularly in biliary reconstruction, have played a central role in improving outcomes after pediatric liver transplant. Biliary complications remain among the most common postoperative challenges in this population, with various reconstruction techniques such as duct-to-duct anastomosis and Roux-en-Y hepaticojejunostomy being used per recipient and graft characteristics.^10-12 Outcomes from single-center experiences have contri-buted significantly to optimizing these techniques and understanding risk factors for graft failure and complications.^13,14 These surgical and technical consi-derations are especially relevant in BA, where prior hepatoportoenterostomy and altered biliary anatomy may further complicate transplant outcomes.
Recent national data have also revealed that socioeconomic disadvantage independently affects disease presentation and early management, with neighborhood deprivation linked to delayed referral, less likelihood of hepatoportoenterostomy, and lower native liver survival rates, regardless of patient race.¹⁵ Overall, these findings indicate a connection between demographic and socioeconomic factors and the incidence and early course of BA, highlighting that these associations likely reflect the influence of social, environmental, and health care access factors rather than purely biological factors.
Evidence from US-based registries continues to highlight ongoing racial and ethnic disparities across the pediatric liver transplant process, including access to LD transplants, waitlist outcomes, and posttransplant survival. Analyses from national transplant registries have shown that that Black children are significantly less likely to receive LD liver transplants compared with White children, despite similar waitlist mortality rates. This finding suggests differences in access to donor resources rather than disease severity.¹⁶ Further analyses from the Scientific Registry of Transplant Recipients have shown higher unadjusted waitlist mortality and lower chances of receiving an LD transplant among Black and Hispanic children. These disparities decreased considerably after adjusting for socioeconomic status, insurance coverage, and disease severity at listing, pointing to social determinants of health rather than biological factors.^17,18 Although some recent cohort data have shown progress toward greater equity, historical registry data still document notable racial differences in long-term graft and patient outcomes.¹⁹ Although data focused on BA have mostly addressed transplant use patterns and center factors, current United Network for Organ Sharing (UNOS) data have shown that BA remains a leading reason for pediatric liver transplants in the United States, making it a pertinent group for studying access and outcome disparities.
Understanding how demographic factors such as race and sex and policy frameworks affect outcomes is crucial for personalizing care and addressing disparities. In this study, we aimed to elucidate these connections by using population-level data to guide targeted interventions and promote equity in BA management.

Materials and Methods

Study design
We used the UNOS database to conduct a retros-pective cohort analysis of pediatric liver transplant recipients with BA. The data spanned from January 1, 2015, through December 30, 2024.

Population
For our analyses, we included pediatric patients (aged ≤18 years) who underwent liver transplant for BA. Among 1382 pediatric liver transplant recipients, 857 (6%) were female. The racial composition was 624 (45.2%), 260 (18.8%), 311 (22.5%), 112 (8.1%),and 75 (5.4%) for non-Hispanic White, Black, Hispanic/Latino, Asian, and Other, respectively.

Study outcomes
Our primary outcomes were graft failure and mortality. Graft failure was defined as the need for retransplant or death with a nonfunctioning graft. Mortality was defined as death from any cause following liver transplant. Our secondary outcomes included acute rejection (at index hospitalization and at 1 year), total preservation time, donor and organ sharing characteristics, distance between the donor hospital and transplant center, and socioeconomic markers such as insurance status.

Covariates
We analyzed the following recipient variables: age group (<1, 1-3, 4-6, 7-10, and >10 years), sex, race and ethnicity (White, Black, Hispanic/Latino, Asian, and Other), body mass index (BMI), pretransplant diagnosis, insurance type, and retransplant status. Recipient disease severity was captured with Pediatric End-Stage Liver Disease (PELD) scores for candidates younger than 12 years and with Model for End-Stage Liver Disease scores for those aged 12 years and older. We analyzed the following donor-related variables: age, sex, race, donor type (living vs deceased), BMI, results of donor liver function tests, and cause of death. Transplant and posttransplant characteristics included the distance between the donor hospital and the transplant center, total preser-vation time, length of hospital stay after transplant, induction therapy (anti-thymocyte globulin and interleukin 2 receptor antagonist), and maintenance immunosuppressive regimen (calcineurin inhibitor [CNI], mycophenolate mofetil [MMF], prednisone).

Statistical analyses
We compared recipient, donor, and transplant characteristics for sex and race groups by using t tests and Wilcoxon-Mann-Whitney (sex) or ANOVA (race) for continuous variables and χ² and the Fisher exact tests for categorical variables. We analyzed patient and graft survival rates and recurrence-free rates (at 3 months, 6 months, and 1, 3, and 5 years posttransplant). We determined survival curves and estimates for these outcomes through the Kaplan-Meier product-limit method. For the survival analysis, days to graft failure and patient death were the endpoints. Recipients who did not experience any of these endpoints, including death (for graft failure), or whose health or graft status was unknown were censored on the last follow-up or the last day of the analysis. Median follow-up was 1693 days for graft survival and 1741 days for patient survival. We performed multivariable Cox regression analyses for clinically suspected risk factors, with the analysis performed separately for LD and DD transplants. We used STATA version 15 for analyses, with statistical significance defined as a two-tailed P < .05.
This study was exempt from institutional review board review because data relied exclusively on deidentified Organ Procurement and Transplantation Network registry data. All organs were procured in accordance with US regulations, with informed consent obtained from donors or their next of kin. No organs in this analysis were sourced from executed prisoners or prisoners of conscience.

Results

Sex-based outcomes
Among 1382 pediatric liver transplant recipients with BA, no significant sex-based differences were observed in female versus male pediatric transplant recipients, respectively, for acute rejection during hospitalization (12.9% vs 11.4%; P = .379), 1-year rejection rates (21.8% vs 23.2%; P = .518), or graft survival at 1, 3, and 5 years (P = .689, log-rank test) (Table 1). Kaplan-Meier survival curves confirmed comparable graft and patient survival between sexes (Figure 1). Recipient BMI, PELD scores, donor characteristics (eg, preservation time, donor age), donor hospital to transplant center distance, organ sharing, and ischemia times also showed no sex-related disparities (all P > .05) (Table 1).

Race-based outcomes
Race was associated with several differences in clinical and socioeconomic characteristics. Black and Hispanic recipients had lower rates of private insurance (20.0% and 21.2%, respectively) compared with White (58.0%) and Asian (64.3%) recipients
(P ≤ .001). Compared with non-Hispanic White recipients, Black recipients had higher PELD scores (17.8 vs 14.4; P ≤ .001), lower use of LDs (16.9% vs. 29.2%; P =.004), and greater reliance on nationally shared organs (33.1% vs 27.1%; P =.026). Among recipients of DD transplants, total preservation time was significantly shorter for non-Hispanic White patients compared with other races (P = .01). Donor hospital to transplant center distance did not differ significantly across racial groups and was not associated with differences in acute rejection, graft failure, or patient survival outcomes. No differences among races were shown in acute rejection during hospitalization (P = .769), 1-year rejection (P = .299), or graft failure from ischemic cholangiopathy
(P = .876) Table 2). Kaplan-Meier survival curves demonstrated com-parable 5-year graft and patient survival rates (Figure 2).
Risk factors for deceased donor transplant
In the multivariate Cox regression analysis of DD transplants (n = 1033), no variables reached statistical significance for prediction of graft failure or mortality. Recipient sex, race, insurance status, PELD score, donor age, ischemia times, immunosuppressive regimen, and organ-sharing pattern were not independently associated with increased graft failure risk or mortality in DD transplants (Table 3 and Table 4).

Risk factors for living donor transplant
For LD transplants (n = 349), 2 independent pre-dictors of graft failure were identified. Black race was associated with a markedly increased risk (hazard ratio = 10.906, P = .009), and increasing donor age was also a significant risk factor (hazard ratio = 1.086, P = .048). No other variables, including sex, immuno-suppressive regimen, PELD score, or insurance status, were associated with graft failure or mortality in LD transplants (Table 5 and Table 6).

Discussion

Our results indicated a complex interaction among clinical, demographic, and donor-related factors affecting outcomes in pediatric liver transplant for BA. Our findings suggest that sex does not appear to be a major independent determinant of transplant outcomes among pediatric liver transplant recipients with BA. Although hormonal profiles have been suggested as possible contributors to sex differences in transplant outcomes, their effects in this cohort appear clinically negligible.^21,22 Moreover, healthier candidates might have been more likely to be selected for transplant, which could mask disparities among sicker patients. Larger, prospective studies with detailed hormonal and socioeconomic data may be useful to validate this and help develop more sex-neutral care approaches.²³
Maintenance immunosuppression regimens, mainly CNI combined with MMF and steroids, or CNI plus steroids, showed no significant differences in graft failure or mortality in multivariable Cox regression analysis. In our cohort, the absence of outcome differences between regimens may have reflected protocol standardization or insufficient power to detect subtle effects, considering that ≤153 recipients received less common regimens (such as CNI-only or CNI+MMF). This finding indicates that, within current pediatric BA practice, the immuno-suppressive strategy is unlikely to be a primary factor driving disparities in posttransplant outcomes.
Pronounced racial and socioeconomic disparities were evident in several pretransplant and donor-related factors. Our findings of Black patients having lower significantly rates of LD transplant (16.9% vs 29.2%; P = .004) and being more dependent on nationally shared organs (33.1% vs 27.1%; P = .026) than White patients aligned with prior national re-gistry data showing reduced access to LD transplant among marginalized groups.^24,25 Such disparities likely resulted from complex barriers, including limited awareness of LD transplant, perceived lack of knowledge despite similar actual understanding, differing perceptions of transplant necessity, and self-evaluations based on assumptions of medical unsuitability.²⁴
Similarly, our study showed that Black and Hispanic recipients had lower private insurance coverage rates (20.0% and 21.2%, respectively) than White (58.0%) or Asian (64.3%) recipients (P < .001). In early analyses from the UNOS database during the initial PELD period, publicly insured children with BA had higher waitlist mortality and worse patient and graft survival rates posttransplant compared with privately insured children; these associations remained even after adjusting for disease severity and were partly due to reduced access to living donation and longer cold ischemia times.²⁶ Recent research has also emphasized the effects of social adversity and socioeconomic vulnerability on posttransplant outcomes in pediatric liver transplant recipients.²⁷ However, our findings showed no significant differences in graft failure or mortality based on insurance status. This difference may have been as the result of changes over time, including updated allocation practices and improvements in peri- and posttransplant care, which may have reduced insurance-related outcome disparities in more contemporary populations. Of note, associations between race and transplant outcomes in our study were evaluated using multivariable models adjusted for PELD score, insurance status, and donor type, ensuring that differences in disease severity at transplant and access to living donation were considered when evaluating racial effects on posttransplant outcomes.
Although Black recipients in our cohort showed higher disease severity at transplant, as indicated by higher mean PELD scores, and had different donor characteristics, our results showed no significant differences in graft failure, rejection, or mortality. These findings aligned with previous research indicating that greater pretransplant disease severity does not necessarily lead to worse posttransplant outcomes in pediatric liver transplants. Registry studies have shown that prioritizing children with higher PELD scores does not compromise post-transplant graft or patient survival and supports allocation strategies that favor the sickest children.^28,29 In addition, national UNOS data have shown that acceptable outcomes can be achieved even in critically ill pediatric recipients, including those on advanced life support at transplant.³⁰ Long-term registry data have further confirmed ongoing improvements in graft and patient survival despite rising recipient risk profiles over time.³¹
Living donor liver transplant plays a crucial role in managing BA, but outcomes seem affected by donor and recipient traits. In our cohort, Black race emerged as a strong independent predictor of graft failure among LD liver transplant recipients (HR = 10.906, P = .009). Prior research has shown that Black recipients have worse graft survival after LD liver transplant, likely due to cumulative disadvantages in access to pretransplant optimization, center expertise, and posttransplant surveillance.³² These findings suggest that, although LD liver transplant offers significant benefits, its success may depend on highly optimized perioperative and posttransplant care, especially in high-risk groups.³³ These observations match our results, where LD liver transplant recipients who are Black started with higher PELD scores and later had a significantly increased risk of graft loss.
In our analysis, donor age was a significant factor influencing LD liver transplant outcomes, with older donors associated with a higher risk of graft failure (HR = 1.086, P = .048). The differences in donor age mostly reflect allocation strategies rather than inherent donor risk. Pediatric recipients with BA are usually matched with younger DDs due to size- and age-based allocation practices that favor pediatric grafts for pediatric recipients,^34,35 resulting in a higher likelihood of younger DD utilization, parti-cularly among infants and young children with BA.³⁶ Conversely, LD liver transplant introduces a distinct donor age profile driven predominantly by adult parental donors, a pattern seen consistently in large BA groups across various regions.^36,37 Therefore, donor age should be understood in the context of donor type and allocation pathways, not as an isolated risk factor, since its effect on outcomes differs depending on whether the graft is from a DD or LD, with older donor age presenting different risks in each case.^38,39
The findings of our study should also be interpreted within the broader context of surgical evolution and technical variability in pediatric liver transplant. Early single-center experiences with living-related and segmental liver transplant demonstrated that outcomes are highly dependent on surgical expertise, graft selection, and perio-perative management.^7-9 These foundational studies highligh-ted both the benefits and challenges of LD liver transplant, including increased technical complexity and the importance of meticulous donor and recipient selection. In this context, the observed association between donor age and graft failure in our cohort is consistent with prior reports emphasizing the effects of graft quality and regenerative capacity in partial liver grafts, particularly in pediatric recipients.¹⁴
Total graft preservation time demonstrated racial variation across the cohort, with this difference driven primarily by DD transplant. Among DD grafts, total preservation time differed significantly by race (P = .010), with Non-Hispanic White recipients experiencing shorter mean preservation times (6.91 ± 2.16 h) compared with Black (6.52 ± 2.22 h), Hispanic (7.17 ± 2.32 h), Asian (7.36 ± 2.62 h), and Other race recipients (7.22 ± 2.51 h). In contrast, preservation time among LD transplants was uni-formly short and did not differ significantly by race (White: 2.04 ± 1.34 h, Black: 2.03 ± 2.24 h, Hispanic: 2.51 ± 1.65 h, Asian: 2.35 ± 1.41 h, Other: 2.12 ± 1.25 h; P = .239). Despite the observed differences in DD preservation time, total preservation time was not independently associated with graft failure or patient mortality in multivariable analyses. These findings suggest that, within the contemporary pediatric liver transplant era, modest variations in preser-vation time, particularly within the range observed for DD grafts, do not translate into inferior post-transplant outcomes. Nonetheless, the presence of racial variation in DD preservation time highlights persistent differences in organ allocation pathways and transplant logistics that warrant continued evaluation to ensure equitable access to optimal graft conditions.
Technical factors such as biliary reconstruction methods and postoperative complications must also be considered when interpreting transplant outco-mes in BA. Previous studies have shown that biliary complications remain a significant contributor to morbidity following pediatric liver transplant, with outcomes influenced by surgical technique, graft type, and center experience.^10-12 Although our analysis did not directly evaluate specific reconstruc-tion strategies, the interaction between donor type, preservation time, and graft outcomes observed in our study may partly reflect these underlying technical variables. Integrating large-scale registry analyses with detailed surgical data in future studies will be essential to better delineate the relative contributions of technical and systemic factors to transplant outcomes.

Limitations
Our study had several limitations, including the retrospective design, which could have allowed potential selection and information biases. Patients who are healthier or less complex may have been more likely to be listed, which could lead to an underestimation of disparities in higher-risk groups. Several socioeconomic factors available in the UNOS database (like education and citizenship) were excluded due to substantial missing data, reducing their reliability and making accurate imputation impossible. As a result, our analysis assumed data were missing at random and focused on variables with sufficient information, such as recipient sex and race and ethnicity. Reporting based on registry data may vary by center, potentially masking differences in surgical techniques, perioperative care, posttransplant monitoring, and adherence to antithrombotic strate-gies. Changes over the decade-long study period, including shifts in immunosuppression protocols and increased access to living donation, could also affect outcomes. Another limitation was the small number of patients on less common maintenance regimens, thus limiting the ability to analyze regimen-specific effects in BA-specific protocols. These limitations highlight the importance of prospective, multicenter studies with comprehensive data to confirm these findings.

Conclusions

This contemporary national analysis showed that posttransplant outcomes are equitable between sexes among pediatric transplant recipients with BA. In addition, although Black recipients tended to have more severe disease and different donor characteristics, our findings showed that these factors did not lead to worse graft or patient survival after adjustment. Nonetheless, ongoing disparities in access to LD transplant and varied risk profiles in LD liver transplant highlight the need for targeted strategies to improve donor selection, perioperative care, and posttransplant monitoring. These results stress the importance of addressing structural and logistical barriers to achieve fair outcomes in pediatric liver transplant.

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