OBJECTIVE:To characterize barriers and facilitators influencing caregiver decision-making regarding living donor liver transplantation (LDLT) for children with end-stage liver disease. STUDY DESIGN:This qualitative study used semistructured, in-depth interviews conducted between May 2023 and March 2025 with caregivers of pediatric liver transplant recipients enrolled in the Social & Contextual Impact on Children Undergoing Liver Transplantation study cohort. Interviews were recorded and professionally transcribed, then independently coded by 3 reviewers using a codebook informed by the capability, opportunity, motivation - behavior model, an implementation science framework. Codes were compared and reconciled to generate themes. RESULTS:Eighteen caregivers participated; 50% reported household incomes <150% of the federal poverty level. Seven themes emerged: (1) insufficient time to comprehend transplant options, (2) perceived or actual lack of eligible donors in caregiver's social network, (3) concern about donor health consequences, (4) challenge of being both a caregiver and donor, (5) discordance between discomfort asking others to donate and response received, (6) limited knowledge about differences between whole and split liver, and (7) the appeal of flexible surgical scheduling offered by LDLT. These themes highlight the interplay between cognitive, social, and practical factors influencing pursuit of living donation. CONCLUSIONS:Strategies to support decision-making about LDLT should include counseling about the procedure's benefits early in the transplant evaluation process, helping identify nondirected donors and reducing the caregiving burden during the donor recovery period. Such efforts should prioritize under-resourced families to enhance equitable outcomes for children with end-stage liver disease. CLINICAL TRIAL REGISTRATION:www. CLINICALTRIALS:gov NCT04551742.

BACKGROUND:Patient-reported outcomes are increasingly recognized as essential complements to biological indices in chronic disease including pediatric liver transplantation. However, clinicians lack clear thresholds to determine when changes in patient-reported outcome measure (PROM) scores represent clinically meaningful change. Establishing minimal clinically important difference (MCID) values is critical to interpret longitudinal PROM data and guide action. The Starzl Network Patient Reported Outcomes (SPaRO) study provided a unique opportunity to derive MCID estimates of the Pediatric Liver Transplant Quality of Life (PeLTQL) questionnaire. METHODS:In SPaRO, English- or Spanish-speaking pediatric LT recipients aged 8-18 years and at least 1 year post-LT were recruited from 7 Starzl Network for Excellence in Pediatric Transplantation (SNEPT) sites. Participants and caregivers completed the PeLTQL (self- and proxy-report) questionnaire twice via a mobile application or web-based platform. MCIDs were estimated using anchor-based and distribution-based methods including predictive modeling. RESULTS:A total of 98 patients and 86 caregivers completed two PeLTQL assessments between March 2022 and October 2023. Triangulated MCID values for the total score (TS) were 6.4 (self-report) and 5.6 (proxy-report). Predictive modeling yielded estimates of 7.7 (self) and 6.8 (proxy). CONCLUSIONS:In this multicenter cohort, MCID thresholds for the PeLTQL TS were approximately 6-8 points (self-report) and 6-7 points (proxy-report), consistent with prior single-center estimates. Changes in the PeLTQL TS of greater than 6 points may help clinicians identify patients who warrant closer attention. Prospective validation using an independent anchor is underway. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT05241847.

OBJECTIVE:To test the hypothesis that community deprivation, race, and ethnicity lead to decreased likelihood of undergoing hepatoportoenterostomy, older age at surgery, decreased likelihood of achieving successful bile drainage, and lower rates of native liver survival for infants with biliary atresia. METHODS:We analyzed a prospectively enrolled cohort of infants with biliary atresia from the Childhood Liver Disease Research Network (ChiLDReN) that reflects the demographics of the US population. We tested the association between demographic, clinical, and anatomic variables and the probability of undergoing hepatoportoenterostomy, age at surgery, success of surgical intervention, and native liver survival using linear and logistic regression. RESULTS:Seven hundred nineteen infants with biliary atresia from 15 centers met study inclusion criteria and 672 (93.5%) underwent hepatoportoenterostomy. After adjusting for potential confounders, Asian race (odds ratio [OR] = 0.21, 0.06-0.77), Hispanic ethnicity (OR = 0.33, 0.14-0.76), and community deprivation (0.71 per 0.1 increase, 0.52-0.97) were independently associated with decreased probability of undergoing hepatoportoenterostomy. Each 10% increase in community deprivation increased the age at hepatoportoenterostomy by approximately two-and-one-third days (estimate 2.31; P = .48). Black/African American infants were approximately 9 days older than white infants at the time of operation (estimate 9.19; P = .01), while age at hepatoportoenterostomy (OR = 0.90, P = .01) and successful bile drainage at 3 months (OR = 26.15, P < .01) were independently associated with native liver survival. CONCLUSIONS:Community deprivation, race, and ethnicity are associated with both lower hepatoportoenterostomy rates and older age at the time of operation, whereas clinical and anatomic variables are associated with successful biliary drainage and native liver survival.

BACKGROUND AND AIMS:Liver transplantation is a lifesaving, standard of care intervention for infants, children, and adolescents with liver tumors, inborn errors of metabolism, and irreversible liver disease caused by a wide spectrum of liver conditions. The American Association for the Study of Liver Diseases (AASLD) last published guidelines for the evaluation and selection of pediatric liver transplant candidates in 2014. This 2026 update aims to provide evidence-based recommendations that reflect current best practices and evolving clinical knowledge. METHODS:A multidisciplinary writing group of pediatric liver transplant experts and a medical librarian was convened by AASLD, with guidance by its Practice Guidelines Development Policy, and in collaboration with the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the American Society of Transplantation (AST). We conducted a systematic global literature review, formulated key clinical questions, and developed recommendations. Each recommendation was graded using the Oxford Centre for Evidence-Based Medicine framework and categorized by strength through a consensus voting process. CONCLUSION:This document provides clear, evidence-based guidelines on the transplant evaluation process and journey in infants, children, and adolescents. It outlines indications, contraindications, and barriers to transplantation based on robust, relevant published data. It offers best practices for pre-transplant assessment, organ allocation, and strategies to optimize survival, while allowing flexibility for individual clinical scenarios.

BACKGROUND:Frailty is a phenotype of cumulative decline leading to decreased physiologic reserve and vulnerability to stressors. Frailty is associated with adverse outcomes after liver transplantation (LT) in adults, but similar data are not available in children. A prospective multicenter study previously determined that frailty is present in 46% of children with end-stage liver disease (ESLD). We utilized this cohort to evaluate the impact of pre-transplant frailty on post-LT outcomes. METHODS:The study included pediatric participants from the original frailty study across 10 North American transplant centers who had subsequently undergone LT. Clinical outcomes were collected up to 1 year post LT. Participants were stratified by their pre-transplant frailty score (defined by a pre-LT frailty score of ≥ 6.0) and long-term outcomes were compared between groups. RESULTS:28 (60.7% female, 46.4% biliary atresia) pediatric LT recipients were included, and 54% of children met criteria for frailty (n = 15). Baseline characteristics were comparable between groups; however, those with frailty were significantly more likely to have pre-transplant failure to thrive (33.3% vs. 0%, p = 0.044). Thirty-four hospital readmissions (22 in frail and 12 in non-frail children) occurred in 20 patients. Higher pre-transplant frailty scores were also significantly associated with an increased number of readmissions after transplantation (p = 0.034). CONCLUSIONS:Pediatric frailty may be associated with the adverse outcome of increased frequency of hospitalization in the first year after pediatric liver transplantation. These data support the concept that frail children should be identified and targeted for prehabilitation prior to LT.

BACKGROUND:Liver transplant (LT) waitlist mortality occurs in 10% of children; innovative strategies to expand access to LT can be lifesaving. METHODS:Outcomes of ABO incompatible (ABOi) LT performed between 1999 and 2023 at a high-volume center were compared to ABO compatible (ABOc) LT. RESULTS:25 ABOi LT were performed among 270 LT; 72% were listed with status 1/1A/1B or a median pediatric end-stage liver disease/model for end-stage liver disease of 40 (IQR 32,41). Time on the waitlist for ABOi recipients was shorter (median 11 days [IQR 4,46]) compared to ABOc (113 days [IQR 39,252], p < 0.001). ABOi graft types were 64% technical variants (including 2 living donor grafts) and 36% whole; 52% received a duct-duct biliary anastomosis. There were no statistically significant differences in 1/5/10-year patient survival [ABOi: 87,87,87% vs. ABOc: 96,94,89%, p = 0.6] or graft survival [ABOi: 87,82,82% vs. ABOc: 92,86,80%, p = 0.9]. When compared to ABOc, there were no statistically significant differences in vascular complications, bile leaks, or acute T-cell-mediated rejection with ABOi LT. Biliary strictures were diagnosed in 43% of ABOi LT and more frequently than in ABOc (20%, p = 0.0495). CONCLUSIONS:ABOi LT can offer children on the waitlist a survival advantage through shorter waiting time. ABOi LT can be performed safely with a low rate of vascular complications similar to ABOc LT.

OBJECTIVE:To evaluate the relationship between patient outcomes and a discrepancy score, a new way to quantify caretaker vs child discrepancies on patient-reported outcome measures (PROMs). STUDY DESIGN:Children aged between 8 and 18 years, at least 1 year from a primary liver transplantation, and their primary adult caretaker were recruited in a prospective, hypothesis-driven cohort study conducted in 7 centers (USA, Canada) from the Starzl Network for Excellence in Pediatric Transplantation. A novel electronic application computed a "discrepancy score": the absolute cumulative value of each year's difference in scores between child and caretaker responses on a Health-Related Quality of Life (HRQoL) questionnaire. Liver and HRQoL outcomes were also evaluated. RESULTS:Of 200 enrolled, 160 patients/140 dyads answered the questionnaire at least once; 101 patients/85 dyads answered twice. Median age was 13 years, and 60.6% were females. HRQoL was not associated with liver outcomes but was associated with discrepancy scores in both the first and second administration: Pearson correlation -0.469 (95% confidence interval: -0.588, -0.328, P < .01) and -0.347 (95% confidence interval: -0.520, -0.143, P < .01), respectively. CONCLUSIONS:Quantifying differences between child and caretaker PROMs in a "discrepancy score" is a novel way to interpret PROM results. Decreasing discrepancies could be a reasonable clinical target.

Pediatric liver retransplantation (rLT) has historically shown poorer outcomes compared to primary liver transplantation (pLT). Comprehensive studies assessing outcomes for pediatric candidates for rLT under the modern allocation policy are lacking. Organ Procurement and Transplantation Network data from January 1, 2010, to December 31, 2022, were obtained; exclusion criteria included candidates >= 18 years of age and those listed or transplanted for multiple organs. A total of 7645 children met the inclusion criteria, including 7162 candidates for pLT and 483 candidates for rLT. The candidates for rLT, despite a shorter median waitlist time to transplant (6.5 vs. 54 d for pLT), had significantly higher waitlist dropout rates and worse posttransplant outcomes. Vascular complications were the most common reason for primary graft failure. The small size of the recipient was a significant risk factor. Among those retransplanted, the timing of relisting was significantly associated with outcomes, with those relisted within 30 days from the pLT demonstrating considerably worse outcomes. Our findings emphasize the importance of a center's surgical expertise in performing transplants on small recipients to minimize postoperative complications leading to primary graft failure. Once relisted, the timing of suitable organ availability was vital. The opportunity for technical variant grafts is crucial to capture every potential transplant opportunity that could ultimately decide between life and death.

Fontan-associated liver disease is a unique form of congestive hepatopathy occurring after Fontan palliation of single functional ventricle congenital heart disease. Although congestive hepatic fibrosis post-Fontan has been scored with various histologic systems, none have been validated in this population. The Congestive Hepatic Fibrosis Score (CHFS) was developed to assess liver disease in congestive hepatopathy secondary to chronic right heart failure and is a promising tool for staging congestive hepatic fibrosis post-Fontan. We sought to validate the CHFS in this setting and to examine clinical, laboratory, and hemodynamic parameters impacting the development of Fontan-associated liver disease. Three pathologists reviewed liver biopsies from 42 pediatric and adult post-Fontan patients, with review of clinical, laboratory, and hemodynamic parameters. CHFS and METAVIR fibrosis scores divided biopsies into identical clusters of low stage (stages 0, 1, and 2) and high stage (stages 3 and 4) fibrosis. Interobserver variability for both scores was moderate. Patients with high-stage fibrosis had significantly longer mean time since Fontan. Female patients were more likely to have high-stage fibrosis. Hemodynamic variables had no significant differences between the groups. We conclude that CHFS is a valid scoring method in pediatric and adult patients post-Fontan. Time since Fontan is the best predictor of severe hepatic fibrosis, but much interpatient variation is not explained by any of the identified clinical, laboratory, or hemodynamic parameters. Liver biopsy, therefore, remains the best means of assessing liver fibrosis in post-Fontan patients.

Pediatric healthcare delivery systems are increasingly employing navigators, community health workers, and social workers to improve child and household access to healthcare and social services, with the goal of decreasing healthcare inequities. However, navigation strategies are understudied in pediatric liver transplantation. We used human-centered design methods, eliciting the perspectives of caregivers and transplant team members, to design a navigator role for pediatric liver transplantation. We enrolled 10 caregivers reporting household social risks and 6 transplant practitioners from 7 US transplant centers. We conducted 8 virtual focus groups between September 12, 2023, and January 31, 2024, to define gaps in care and ideate on how lay navigators could mitigate those challenges. We utilized design tools to elicit stakeholders' values and preferences. We recorded the focus groups and qualitatively analyzed audio transcripts to thematically identify essential job functions. Most caregivers reported earning an annual household income <$59,000 (70.0%), living below the federal poverty line (55.6%), and experiencing financial strain (80.0%). Caregivers wanted navigators to help them: (1) access community-based resources, (2) build longitudinal relationships with the healthcare team, (3) prepare them for appointments, (4) communicate with their child's school, and (5) address cultural differences between families and transplant practitioners. The transplant team wanted navigators to help caregivers: (1) address families' socioeconomic resource needs, (2) coordinate appointment scheduling, and (3) facilitate cultural and language-concordant care. Using structured design methodology, we designed a prototype navigator role for pediatric liver transplant care teams. Future studies should test the effectiveness of this navigator role in improving posttransplant outcomes.

BACKGROUND:Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs. METHODS:Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3. RESULTS:All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine. CONCLUSIONS:The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron.

BACKGROUND AND AIMS:High levels of serum matrix metalloproteinase-7 (MMP-7) have been linked to biliary atresia (BA), with wide variation in concentration cutoffs. We investigated the accuracy of serum MMP-7 as a diagnostic biomarker in a large North American cohort. APPROACH AND RESULTS:MMP-7 was measured in serum samples of 399 infants with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays. The discriminative performance of MMP-7 was compared with other clinical markers. On the single-plex assay, MMP-7 generated an AUROC of 0.90 (CI: 0.87-0.94). At cutoff 52.8 ng/mL, it produced sensitivity = 94.03%, specificity = 77.78%, positive predictive value = 64.46%, and negative predictive value = 96.82% for BA. AUROC for gamma-glutamyl transferase = 0.81 (CI: 0.77-0.86), stool color = 0.68 (CI: 0.63-0.73), and pathology = 0.84 (CI: 0.76-0.91). Logistic regression models of MMP-7 with other clinical variables individually or combined showed an increase for MMP-7+gamma-glutamyl transferase AUROC to 0.91 (CI: 0.88-0.95). Serum concentrations produced by time resolved fluorescence energy transfer differed from single-plex, with an optimal cutoff of 18.2 ng/mL. Results were consistent within each assay technology and generated similar AUROCs. CONCLUSIONS:Serum MMP-7 has high discriminative properties to differentiate BA from other forms of neonatal cholestasis. MMP-7 cutoff values vary according to assay technology. Using MMP-7 in the evaluation of infants with cholestasis may simplify diagnostic algorithms and shorten the time to hepatoportoenterostomy.

Children from minoritized/socioeconomically deprived backgrounds suffer disproportionately high rates of uninsurance and graft failure/death after liver transplant. Medicaid expansion was developed to expand access to public insurance. Our objective was to characterize the impact of Medicaid expansion policies on long-term graft/patient survival after pediatric liver transplantation. All pediatric patients (<19 years) who received a liver transplant between January 1, 2005, and December 31, 2020 in the US were identified in the Scientific Registry of Transplant Recipients (N = 8489). Medicaid expansion was modeled as a time-varying exposure based on transplant and expansion dates. We used Cox proportional hazards models to evaluate the impact of Medicaid expansion on a composite outcome of graft failure/death over 10 years. As a sensitivity analysis, we conducted an intention-to-treat analysis from time of waitlisting to death (N = 1 1901). In multivariable analysis, Medicaid expansion was associated with a 30% decreased hazard of graft failure/death (hazard ratio, 0.70; 95% confidence interval, 0.62, 0.79; P < .001) after adjusting for Black race, public insurance, neighborhood deprivation, and living in a primary care shortage area. In intention-to-treat analyses, Medicaid expansion was associated with a 72% decreased hazard of patient death (hazard ratio, 0.28; 95% confidence interval, 0.23-0.35; P < .001). Policies that enable broader health insurance access may help improve outcomes and reduce disparities for children undergoing liver transplantation.

SARS-CoV-2 infection during the Omicron period was frequent amongst a cohort of vaccinated pediatric solid organ transplant recipients (pSOTRs) despite robust anti-receptor-binding domain (anti-RBD) antibody response, suggesting poor neutralizing capacity against Omicron subvariants. Breakthrough infections among pSOTRs were overall limited in severity.

BACKGROUND:Pediatric liver transplantation for small recipients presents significant challenges, particularly in securing suitably sized donor organs. This case report illustrates the feasibility of performing an in situ split procurement in an 18.5-kg toddler, the smallest recorded case in the OPTN database to date, for a critically ill 8-week-old infant recipient. CASE PRESENTATION:An 8-week-old infant with severe hepatitis of unknown etiology was urgently listed as Status 1A. An organ offer from a 3.5-year-old donor, requiring a reduction procedure, became available 1939 nautical miles away. Instead of a back-table reduction procedure, we performed an in situ split to reduce cold ischemic time given the distance. The recipient surgery was started ahead of the organ's arrival, and the recipient was ready for graft implantation upon the organ's arrival, resulting in a total of 510 min of cold ischemic time. Post-operatively, the graft did not show signs of significant injury or dysfunction, which expedited recovery from her other medical conditions. CONCLUSIONS:In situ split liver procurement is an invaluable tool for pediatric centers as it effectively provides more graft options for pediatric patients on the waitlist. Additionally, in situ split can offer significant benefits in optimizing recipient surgery, especially when the donor is located at an extreme distance. Despite these benefits, in situ split is not currently widely utilized across transplant centers. Addressing the logistical challenges associated with this technique is crucial for broader implementation and improved patient outcomes.

BACKGROUND:We examined the combined effects of donor age and graft type on pediatric liver transplantation outcomes with an aim to offer insights into the strategic utilization of these donor and graft options. METHODS:A retrospective analysis was conducted using a national database on 0-2-year-old (N = 2714) and 3-17-year-old (N = 2263) pediatric recipients. These recipients were categorized based on donor age (≥40 vs <40 years) and graft type. Survival outcomes were analyzed using the Kaplan-Meier and Cox proportional hazards models, followed by an intention-to-treat (ITT) analysis to examine overall patient survival. RESULTS:Living and younger donors generally resulted in better outcomes compared to deceased and older donors, respectively. This difference was more significant among younger recipients (0-2 years compared to 3-17 years). Despite this finding, ITT survival analysis showed that donor age and graft type did not impact survival with the exception of 0-2-year-old recipients who had an improved survival with a younger living donor graft. CONCLUSIONS:Timely transplantation has the largest impact on survival in pediatric recipients. Improving waitlist mortality requires uniform surgical expertise at many transplant centers to provide technical variant graft (TVG) options and shed the conservative mindset of seeking only the "best" graft for pediatric recipients.