Intraoperative renal replacement therapy during liver transplantation in children: Safety, efficacy and impact on survival.

BACKGROUND: Intraoperative Continuous Renal Replacement Therapy (iCRRT) can prevent life-threatening complications, facilitate fluid management, and maintain metabolic homeostasis during liver transplantation (LT) in adults. There is a paucity of data in pediatric LT. We evaluated the safety, efficacy, and impact on survival of iCRRT in pediatric LT. METHODS: We conducted a retrospective cohort study of all children requiring CRRT pre-OLT at a quaternary children's hospital from 2014 to 2022. Demographic characteristics, intraoperative events, and post-LT outcomes were compared between those who received iCRRT and those who did not. RESULTS: Out of 306 patients who received LT, 30 (10%) were supported with CRRT at least 24 h prior to LT, of which 11 (36%) received iCRRT. The two cohorts were similar in demographics, diagnosis of liver disease, and severity of illness. The iCRRT patients experienced massive blood loss and increased transfusion requirements. There was no difference in intraoperative metabolic balance. One-year post-LT mortality rates were similar. CONCLUSION: ICRRT is safe in critically ill children with pre-LT renal dysfunction. It optimizes fluid and blood product resuscitation while maintaining metabolic homeostasis. Candidates need to be carefully chosen for this highly resource-intensive therapy to benefit this fragile population.

Postoperative outcomes of acute-on-chronic liver failure in infants and children with biliary atresia.

INTRODUCTION: Acute-on-chronic liver failure (ACLF) is associated with increased mortality and morbidity in patients with biliary atresia (BA). Data on impact of ACLF on postoperative outcomes, however, are sparse. METHOD: We performed a retrospective analysis of patients with BA aged <18 years who underwent LT between 2011 and 2021 at our institution. ACLF was defined using the pediatric ACLF criteria: ≥1 extra-hepatic organ failure in children with decompensated cirrhosis. RESULTS: Of 107 patients (65% female; median age 14 [9-31] months) who received a LT, 13 (12%) had ACLF during the index admission prior to LT. Two (15%) had Grade 1; 4 (30%) had Grade 2; and 7 (55%) had Grade ≥3 ACLF. ACLF cohort was younger at time of listing (5 [4-8] vs. 9 [6-24] months; p < .001) and at LT (8 [8-11] vs. 16 [10-40] months, p < .001) compared to no-ACLF group. Intraoperatively, ACLF patients had higher blood loss (40 [20-53] vs. 10 [6-19] mL/kg; p < .001) and blood transfusion requirements (33 [21-69] vs. 18 [7-25] mL/kg; p = .004). Postoperatively, they needed higher vasopressor support (31% vs. 10.6%; p = .04) and had higher total hospital length of stay (106 [45-151] vs. 13 [7-30] days; p = .023). Rate of return to the operating room, hospital readmission rates, and 1-year post-LT survival rates were comparable between the groups. CONCLUSION: Despite higher perioperative complications, survival outcomes for ACLF in BA after LT are favorable and comparable to those without ACLF. These encouraging data reiterate prioritization during organ allocation of these critically ill children for LT.

A humanized mouse model for adeno-associated viral gene therapy.

Clinical translation of AAV-mediated gene therapy requires preclinical development across different experimental models, often confounded by variable transduction efficiency. Here, we describe a human liver chimeric transgene-free Il2rg-/-/Rag2-/-/Fah-/-/Aavr-/- (TIRFA) mouse model overcoming this translational roadblock, by combining liver humanization with AAV receptor (AAVR) ablation, rendering murine cells impermissive to AAV transduction. Using human liver chimeric TIRFA mice, we demonstrate increased transduction of clinically used AAV serotypes in primary human hepatocytes compared to humanized mice with wild-type AAVR. Further, we demonstrate AAV transduction in human teratoma-derived primary cells and liver cancer tissue, displaying the versatility of the humanized TIRFA mouse. From a mechanistic perspective, our results support the notion that AAVR functions as both an entry receptor and an intracellular receptor essential for transduction. The TIRFA mouse should allow prediction of AAV gene transfer efficiency and the study of AAV vector biology in a preclinical human setting.

Identifying drivers of cost in pediatric liver transplantation.

Understanding the economics of pediatric liver transplantation (LT) is central to high-value care initiatives. We examined cost and resource utilization in pediatric LT nationally to identify drivers of cost and hospital factors associated with greater total cost of care. We reviewed 3295 children (<21 y) receiving an LT from 2010 to 2020 in the Pediatric Health Information System to study cost, both per LT and service line, and associated mortality, complications, and resource utilization. To facilitate comparisons, patients were stratified into high-cost, intermediate-cost, or low-cost tertiles based on LT cost. The median cost per LT was $150,836 [IQR $104,481-$250,129], with marked variance in cost within and between hospital tertiles. High-cost hospitals (HCHs) cared for more patients with the highest severity of illness and mortality risk levels (67% and 29%, respectively), compared to intermediate-cost (60%, 21%; p <0.001) and low-cost (51%, 16%; p <0.001) hospitals. Patients at HCHs experienced a higher prevalence of mechanical ventilation, total parental nutrition use, renal comorbidities, and surgical complications than other tertiles. Clinical (27.5%), laboratory (15.1%), and pharmacy (11.9%) service lines contributed most to the total cost. Renal comorbidities ($69,563) and total parental nutrition use ($33,192) were large, independent contributors to total cost, irrespective of the cost tertile ( p <0.001). There exists a significant variation in pediatric LT cost, with HCHs caring for more patients with higher illness acuity and resource needs. Studies are needed to examine drivers of cost and associated outcomes more granularly, with the goal of defining value and standardizing care. Such efforts may uniquely benefit the sicker patients requiring the strategic resources located within HCHs to achieve the best outcomes.

Genome-wide association study identifies high-impact susceptibility loci for HCC in North America.

BACKGROUND AND AIMS: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Risk Index Predicts Pediatric Heart Allograft Non-Utilization.

BACKGROUND: Children listed for heart transplantation face the highest waitlist mortality among all solid organ transplant patients (14%). Attempts at decreasing donor allograft non-utilization (41.5%) could potentially decrease waitlist mortality for pediatric heart transplant patients. Our aim was to quantify the non-utilization risk of pediatric donor heart allografts at the time of initial offering. METHODS: Using the United Network of Organ Sharing (UNOS) database, we retrospectively analyzed 8823 deceased donors (≤18 years old) data through univariable and multivariable analysis and logistic regression models. These factors were divided into a training (n = 5882) and validation set (n = 2941). Donor clinical characteristics and laboratory values were used to predict non-utilization of donor hearts. The multivariable analysis used factors that were significant from the univariable analysis (p-value < .05), and the pediatric non-utilization risk index (pDRSI) included significant factors from the multivariable analysis, producing an overall risk score for non-utilization. With these data, we created a non-utilization risk index to predict likelihood of donor allograft non-utilization. RESULTS: From the 24 potential factors that were identified from univariable analysis, 17 were significant predictors (p < .05) of pediatric heart non-utilization in the multivariable analysis. Low left ventricular ejection fraction (odds ratio (OR)-35.3), hepatitis C positive donor (OR-23.3), high left ventricular ejection fraction (OR-3.29), and hepatitis B positive donor (OR-3.27) were the most significant risk factors. The phDSRI has a C-statistic of 0.80 for the training set and 0.80 for the validation set. CONCLUSION: Using over 8000 donors, the phDSRI uses 17 significant risk factors to predict risk of pediatric heart donor allograft non-utilization.

Retrospective Analysis of the Impact of High- and Low-Quality Donor Livers for Patients with High-Acuity Illness.

BACKGROUND Patients with high-acuity liver failure have increased access to marginal and split liver options, owing to historically high waitlist mortality rates. While most research states that donor liver quality has no impact on patients with high-acuity illness, there have been inconsistencies in recent research on how liver quality impacts post-transplant outcomes for these patients. We aimed to quantify donor liver quality with various post-transplantation patient outcomes for patients with high-acuity illness. MATERIAL AND METHODS Using the liver donor risk index (LDRI), model for end stage liver disease (MELD), and clinically relevant recipient factors, we used multivariate logistic regression to analyze how donor liver quality affects varying measures of patient outcomes for 9923 high-acuity patients from June 18, 2013, to June 18, 2022. RESULTS Using LDRI, high-quality livers had a significant protective impact on high-acuity patient mortality, compared with low-quality livers (OR=0.695 [0.549, 0.879], P=0.002). High-quality livers also had significant impact on graft survival (OR=0.706 [0.558, 0.894], P=0.004). Two sensitivity patient mortality analyses, excluding patients with status 1A and hepatocellular carcinoma, showed significant protective findings for high-quality livers. High-quality livers had insignificant outcomes on long-term survivor mortality, length of hospitalization, and primary non-function outcomes, compared with low-quality donor livers. CONCLUSIONS While our findings suggest donor quality has an impact on high-acuity patient outcomes, these findings indicate further research is needed in intent-to-treat analysis on clinical offer data to provide a clearer finding of how donor quality affects patients with high-acuity illness.

Stevens-Johnson syndrome/toxic epidermal necrolysis in an orthotopic liver transplant recipient: a case report.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare spectrum of acute, mucocutaneous drug reactions characterized by epidermal necrosis of the skin and mucous membranes with progressive multiorgan failure. Cutaneous presentation of SJS/TEN is similar to that of acute graft-versus-host disease, creating a diagnostic dilemma in solid-organ transplant recipients presenting with diffuse, erythematous eruptions, skin sloughing, and systemic sequelae, reflective of both diseases. This case report details a 48-year-old woman post-orthotopic liver transplantation (OLT) who developed a diffuse, painful, morbilliform rash with progressive desquamation, along with corresponding pathological analysis indicative of SJS/TEN. There are few documented reports of SJS/TEN in solid-organ transplant recipients, and this case illustrates successful intervention and resolution of SJS/TEN in an OLT recipient while managing intraabdominal sepsis and an episode of acute rejection. Despite its rarity, prompt diagnosis of SJS/TEN and the implementation of tailored therapeutic strategies are crucial in the care of solid-organ transplant recipients.

Estimating risk of prolonged mechanical ventilation after liver transplantation in children: PROVE-ALT score.

BACKGROUND: Children at high risk for prolonged mechanical ventilation (PMV) after liver transplantation (LT) need to be identified early to optimize pulmonary support, allocate resources, and improve surgical outcomes. We aimed to develop and validate a metric that can estimate risk for Prolonged Ventilation After LT (PROVE-ALT). METHODS: We identified preoperative risk factors for PMV by univariable analysis in a retrospective cohort of pediatric LT recipients between 2011 and 2017 (n = 205; derivation cohort). We created the PROVE-ALT score by mapping multivariable logistic regression coefficients as integers, with cutoff values using the Youden Index. We validated the score by C-statistic in a retrospectively collected separate cohort of pediatric LT recipients between 2018 and 2021 (n = 133, validation cohort). RESULTS: Among total 338 patients, 21% (n = 72) were infants; 49% (n = 167) had cirrhosis; 8% (n = 27) required continuous renal replacement therapy (CRRT); and 32% (n = 111) required management in hospital (MIH) before LT. Incidence of PMV post-LT was 20% (n = 69) and 3% (n = 12) required tracheostomy. Independent risk factors (OR [95% CI]) for PMV were cirrhosis (3.8 [1-14], p = .04); age <1-year (8.2 [2-30], p = .001); need for preoperative CRRT (6.3 [1.2-32], p = .02); and MIH before LT (12.4 [2.1-71], p = .004). PROVE-ALT score ≥8 [Range = 0-21] accurately predicted PMV in the validation cohort with 73% sensitivity and 80% specificity (AUC: 0.81; 95% CI: 0.71-0.91). CONCLUSION: PROVE-ALT can predict PMV after pediatric LT with a high degree of sensitivity and specificity. Once externally validated in other centers, PROVE-ALT will empower clinicians to plan patient-specific ventilation strategies, provide parental anticipatory guidance, and optimize hospital resources.

Critical elements of pediatric liver cancer surgery.

The appropriate management of pediatric liver malignancies, primarily hepatoblastoma and hepatocellular carcinoma, requires an in depth understanding of contemporary preoperative risk stratification, experience with advanced hepatobiliary surgery, and a good relationship with one's local or regional liver transplant center. While chemotherapy regimens have become more effective, operative indications more well-defined, and overall survival improved, the complexity of liver surgery in small children provides ample opportunity for protocol violation, inadequate resection, and iatrogenic morbidity. These guidelines represent the distillation of contemporary literature and expert opinion as a means to provide a framework for preoperative planning and intraoperative decision-making for the pediatric surgeon.

Pediatric Acute Liver Failure Secondary to Autoimmune Hepatitis in an Infant With Thrombocytopenia-Absent Radius (TAR) Syndrome: A Case Report.

Thrombocytopenia absent radius (TAR) syndrome is a rare genetic disorder that has been associated with food protein-induced allergic proctocolitis and transient leukemoid reactions, among other manifestations. There has been no prior reports of its association with autoimmune disease, more specifically, autoimmune hepatitis (AIH) or the development of pediatric acute liver failure (PALF). We present a case of an 8-month-old infant with TAR syndrome who presented with PALF, secondary to AIH with elevated liver-kidney microsomal antibody (>1:2560). She received a liver transplant and had a very complicated postoperative course including severe T-cell-mediated rejection, infection, biliary stricture, persistently elevated liver-kidney microsomal antibodies, and antibody-mediated rejection. Ultimately, these complications led to graft failure, severe sepsis, and death. This case highlights a new association of TAR syndrome with AIH and PALF and a potentially aggressive nature of AIH both pre- and post-transplant.

Survival Benefit of Solid-Organ Transplantation: 10-Year Update.

IMPORTANCE: Transplantation has transformed into a burgeoning field that is rapidly evolving to optimize organ distribution and survival outcomes. The years since 2012 (the last comprehensive study) have seen changes in transplantation, such as advances in immunotherapy and novel indices, that necessitate an updated analysis of survival benefit. DESIGN: Our goal was to determine the survival benefit for solid-organ transplants in the United Network for Organ Sharing (UNOS) database for a three decade period and provide updates on advancements since 2012. Our retrospective analysis examined data containing U.S. patient records from September 1, 1987, to September 1, 2021. RESULTS: We found that 3,430,272 life-years were saved over our transplant period (4.33 life-years saved per patient); kidney-1,998,492 life-years; liver -767,414; heart-435,312; lung-116,625; pancreas-kidney-123,463; pancreas-30,575; intestine-7901. After matching, 3,296,851 life-years were saved. Life-years saved and median survival increased for all organs between 2012 and 2021. Compared to 2012, median survival increased in kidney (from 12.4 to 14.76 years), liver (from 11.6 to 14.59), heart (9.5 to 11.73), lung (5.2 to 5.63), pancreas-kidney (from 14.5 to 16.88), pancreas (from 13.3 to 16.10). When compared to 2012, the percent transplanted increased in kidney, liver, heart, lung, and intestine, while pancreas-kidney and pancreas show decreased percent transplanted. CONCLUSION: Our study underscores the tremendous survival benefits of solid organ transplantation (over 3.4 million life-years saved) and shows improvements since 2012. Our study also highlights areas of transplantation, notably pancreas transplants, that may necessitate reinvigorated attention.

Twenty-year survival following lung transplantation.

Background: Lung transplantation median survival has seen improvements due to recognition of short-term survival factors but continues to trail behind other solid organs due to limited understanding of long-term survivorship. Given the creation of the United Network for Organ Sharing (UNOS) database in 1986, it was difficult to accrue data on long-term survivors until recently. This study characterizes factors impacting lung transplant survival beyond 20 years, conditional to 1-year survival. Methods: Lung transplant recipients listed in UNOS from 1987 to 2002 who survived to 1 post-transplant year were reviewed. Kaplan-Meier and adjusted Cox regression analyses were performed at 20 and 10 years to identify risk factors associated with long-term outcomes independent of their short-term effects. Results: A total of 6,172 recipients were analyzed, including 472 (7.6%) recipients who lived 20+ years. Factors associated with increased likelihood of 20-year survival were female-to-female gender match, recipient age 25-44, waitlist time >1 year, human leukocyte antigen (HLA) mismatch level 3, and donor cause of death: head trauma. Factors associated with decreased 20-year survival included recipient age ≥55, chronic obstructive pulmonary disease/emphysema (COPD/E) diagnosis, donor smoking history >20 pack-years, unilateral transplant, blood groups O&AB, recipient glomerular filtration rate (GFR) <10 mL/min, and donor GFR 20-29 mL/min. Conclusions: This is the first study identifying factors associated with multiple-decade survival following lung transplant in the United States. Despite its challenges, long-term survival is possible and more likely in younger females in good waitlist condition without COPD/E who receive a bilateral allograft from a non-smoking, gender-matched donor of minimal HLA mismatch. Further analysis of the molecular and immunologic implications of these conditions are warranted.

Radiological-histopathological discordance in patients transplanted for HCC and its impact on post-transplant outcomes.

BACKGROUND AND AIMS: Contrast-enhanced cross-sectional imaging is the cornerstone in the diagnosis, staging, and management of HCC, including eligibility for liver transplantation (LT). Radiological-histopathological discordance may lead to improper staging and may impact patient outcomes. We aimed to assess the radiological-histopathological discordance at the time of LT in HCC patients and its impact on the post-LT outcomes. METHODS: We analyzed further the effect of 6-month waiting policy on the discordance. Using United Network for Organ Sharing-Organ Procurement and Transplantation Network (UNOS-OPTN) database, we examined the discordance between pre-LT imaging and explant histopathology for all adult HCC patients who received liver transplants from deceased donors between April 2012 and December 2017. Kaplan-Meier methods and Cox regression analyses were used to evaluate the impact of discordance on 3-year HCC recurrence and mortality. RESULTS: Of 6842 patients included in the study, 66.7% were within Milan criteria on both imaging and explant histopathology, and 33.3% were within the Milan based on imaging but extended beyond Milan on explant histopathology. Male gender, increasing numbers of tumors, bilobar distribution, larger tumor size, and increasing AFP are associated with increased discordance. Post-LT HCC recurrence and death were significantly higher in patients who were discordant, with histopathology beyond Milan (adj HR 1.86, 95% CI 1.32-2.63 for mortality and 1.32, 95% CI 1.03-1.70 for recurrence). Graft allocation policy with 6-month waiting time led to increased discordance (OR 1.19, CI 1.01-1.41), although it did not impact post-LT outcome. CONCLUSION: Current practice for staging of HCC based on radiological imaging features alone results in underestimation of HCC burden in one out of three patients with HCC. This discordance is associated with a higher risk of post-LT HCC recurrence and mortality. These patients will need enhanced surveillance to optimize patient selection and aggressive LRT to reduce post-LT recurrence and increase survival.

Surgical Management and Outcomes of Patients with Multifocal Hepatoblastoma.

OBJECTIVE: To compare the outcomes of patients with multifocal hepatoblastoma (HB) treated at our institution with either orthotopic liver transplant (OLTx) or hepatic resection to determine outcomes and risk factors for recurrence. BACKGROUND: Multifocality in HB has been shown to be a significant prognostic factor for recurrence and worse outcome. The surgical management of this type of disease is complex and primarily involves OLTx to avoid leaving behind microscopic foci of disease in the remnant liver. METHODS: We performed a retrospective chart review on all patients <18 years of age with multifocal HB treated at our institution between 2000 and 2021. Patient demographics, operative procedure, post-operative course, pathological data, laboratory values, short- and long-term outcomes were analyzed. RESULTS: A total of 41 patients were identified as having complete radiologic and pathologic inclusion criteria. Twenty-three (56.1%) underwent OLTx and 18 (43.9%) underwent partial hepatectomy. Median length of follow-up across all patients was 3.1 years (IQR 1.1-6.6 years). Cohorts were similar in rates of PRETEXT designation status identified on standardized imaging re-review (p = .22). Three-year overall survival (OS) estimate was 76.8% (95% CI: 60.0%-87.3%). There was no difference in rates of recurrence or overall survival in patients who underwent either resection or OLTx (p = .54 and p = .92 respectively). Older patients (>72 months), patients with a positive porta hepatis margin, and patients with associated tumor thrombus experienced worse recurrence rates and survival. Histopathology demonstrating pleomorphic features independently associated with worse rates of recurrence. CONCLUSIONS: Through proper patient selection, multifocal HB was adequately treated with either partial hepatectomy or OLTx with comparable outcome results. HB with pleomorphic features, increased patient age at diagnosis, involved porta hepatis margin on pathology, and the presence of associated tumor thrombus may be associated with worse outcomes regardless of the local control surgery offered. LEVEL OF EVIDENCE: III.

Selecting DCD Recipients Using Predictive Indices.

Donation after circulatory death (DCD) allografts might represent one of the largest untapped sources of liver allografts. Our aim was to identify independent recipient risk factors that predict mortality in DCD allograft recipients to preselect optimal candidates for successful transplantation. Furthermore, we compared the application of our newly constructed DCD Recipient Selector Index (RSI) score to previously developed models to determine superiority in predicting recipient survival. Methods: Using the Organ Procurement and Transplantation Network database, we performed univariate and multivariate retrospective analyses on 4228 DCD liver allograft recipients. Results: We identified 8 significant factors and incorporated them into the weighted RSI to predict 3-mo survival following DCD liver transplantation with a C-statistic of 0.6971. The most significant recipient risk factors were recipient serum sodium levels >150 mEq/L at transplant, recipient albumin <2.0 g/dL at transplant, and a history of portal vein thrombosis. Because Model for End-Stage Liver Disease (MELD) score components were included as individual predictors, the DCD RSI predicts survival independently of MELD. Upon comparison with 3 previous recipient risk scores-Balance of Risk, Renal Risk Index, Patient-Survival Outcomes Following Liver Transplantation-the DCD RSI was determined to be superior at selecting optimal candidates pre-DCD transplantation, yielding a C-statistic of 0.6971. Conclusions: After verifying the performance of predictive indices for selection of DCD recipients, the DCD RSI is best used to preselect patients for optimized outcomes after DCD transplantation. This can increase utilization of DCD donors by improving outcomes.

Disparate Intent-to-Treat Outcomes for Pediatric Liver Transplantation Based on Indication.

Background: The impact of indication for pediatric liver transplantation on waitlist and post-transplant mortality outcomes is well known, but the impact on intent-to-treat outcomes has not been investigated. Intent-to-treat survival analysis is important in this study because it is more comprehensive, combining the transplant outcomes of waitlist mortality, post-transplant mortality, and transplant rate into a single metric to elucidate any disparities in outcomes based on indication. Methods: Cox regression was used to analyze factors impacting survival in 8,002 children listed for liver transplant in the UNOS database between 2006 and 2016. The Kaplan-Meier method and log-rank test were used to assess differences in waitlist, post-transplant, and intent-to-treat mortality among the top 5 indications of biliary atresia, acute hepatic necrosis, metabolic disorders, hepatoblastoma, and autoimmune cirrhosis. Results: When compared to the reference group of biliary atresia, multivariate analyses showed that every indication was associated with inferior intent-to-treat outcomes except for metabolic disorders. Hepatoblastoma (hazard ratio (HR): 3.73), autoimmune cirrhosis (HR: 1.86), and AHN (HR: 1.77) were associated with significantly increased intent-to-treat mortality. Hepatoblastoma was also associated with increased post-transplant mortality (HR: 3.77) and was the only indication significantly associated with increased waitlist mortality (HR: 6.43). Conclusion: Significant disparity exists across all indications with respect to an increased intent-to-treat mortality, along with an increased post-transplant and waitlist mortality, when compared to the biliary atresia reference group. If further studies validate these findings, a reexamination of the equitable distribution of allografts for transplant may be warranted as well as a focus on disparities in survival after transplant.