Citations

Abstract Objectives Hepatic steatosis impacts the quality of grafts, affecting transplant outcomes. Rising obesity rates and subsequent donor graft steatosis further influence the organ shortage crisis in pediatric liver transplantation (LT). Our study aimed to evaluate how donor steatosis modulates the outcomes of pediatric LT. Methods We analyzed the United Network of Organ Sharing database for transplanted donor grafts from January 01, 2004, to April 30, 2024. We stratified pediatric (≤18 years) LT recipients into steatotic grafts, subdivided into <30% and ≥30%. Graft failure was assessed using Kaplan–Meier curves, and Cox proportional hazards models, with Lasso regression identifying key predictive variables. Gradient‐boosting decision tree was used to assess the level of likelihood importance for post‐LT survival. Results Five hundred and ninety‐five pediatric LT recipients were included; 62 (10.4%) received donors with steatosis levels ≥30%. Survival rates for steatotic grafts ≥30% were 93.5% at 1 year, 89.9% at 5 years, and 84.4% at 10 years, compared to 94.7%, 89.5%, and 85.2% respectively, among steatotic grafts <30% ( p = 0.72, p = 0.92, and p = 0.92). Donor age (adjusted hazard ratio [aHR]: 1.01, 95% confidence interval [CI]: 1.01–1.03), donation after cardiac death (DCD) (aHR: 10.68, 95% CI: 3.27–34.86), and recipient life support (aHR: 1.95, 95% CI: 1.19–3.20) were associated with an increased risk of mortality. Conclusion Steatotic grafts in pediatric patients had acceptable outcomes. Predictors of mortality in steatotic grafts, including donor age, DCD, and recipient life support, underscore the complex interplay of multiple factors in post‐LT outcomes.

Pediatric metabolic dysfunction–associated steatotic liver disease (MASLD) has become more prevalent on a global scale over the last decades and is associated with significant comorbidities in childhood and a 40-fold higher risk of early mortality in young adulthood. MASLD has now become the leading indication for liver transplantation in young adults in the United States. However, pediatric MASLD is still perceived as an indolent condition by many patients, families, and clinicians. In this Call to Action, we aim to raise awareness of pediatric MASLD as a public health crisis. Herein, we describe insufficient screening and disease staging practices, and a lack of accurate non-invasive tests and effective pharmacotherapy, both stemming from a paucity of multicenter clinical trials in pediatric MASLD. We provide clear steps to address this public health emergency by promoting awareness campaigns, educating and empowering patients and families, addressing barriers including access to care, nutritional and exercise support programs, establishing multidisciplinary care, launching community initiatives, and conducting clinical trials in pediatric MASLD for an age-based evaluation of novel diagnostic and therapeutic options. We conclude by highlighting the urgent need for comprehensive public health policies to control the tide of pediatric MASLD and call upon stakeholders to act now.

AbstractPediatric obesity, characterized by a body mass index (BMI) at or above the 95th percentile for age, affects a substantial number of children and adolescents worldwide. Metabolic dysfunction‐associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease, represents a prominent hepatic manifestation of obesity and metabolic syndrome, emerging as the most prevalent hepatic disorder among pediatric patients and a significant contributor to liver transplantation in adults. The escalating prevalence of pediatric MASLD mirrors the alarming rise in childhood obesity rates over recent decades. While lifestyle modifications focusing on dietary changes and increased physical activity constitute the cornerstone of MASLD management, achieving and maintaining significant weight reduction remains challenging. Moreover, disease progression often persists despite standard‐of‐care interventions, warranting exploration into alternative therapeutic strategies. Pharmacological interventions, particularly, glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), have shown promise in addressing pediatric obesity and its associated comorbidities, including MASLD. Recent studies have demonstrated the efficacy of GLP‐1RA in inducing weight loss and improving liver enzyme levels, suggesting a potential role in halting disease progression, and reducing the risk of major adverse liver outcomes. This review provides a comprehensive overview of the current pharmacotherapy landscape for pediatric MASLD, with a focus on novel agents such as GLP‐1RA. Furthermore, the manuscript proposes a practical algorithm to assist in integrating GLP‐1RA into the clinical management of pediatric patients with obesity and MASLD. Despite promising results, further research is warranted to elucidate the long‐term efficacy and safety of GLP‐1RA in pediatric populations.

Pediatric genetic and metabolic liver diseases comprise a broad spectrum of conditions and represent the second most common indication for liver transplantation following biliary atresia. The decision to transplant can be challenging and requires consideration of several factors, including hepatic involvement, extrahepatic manifestations, and anticipated posttransplant outcomes. This review examines pediatric genetic and metabolic liver diseases, their pathophysiology, clinical presentation, and the role of liver transplantation.

Abstract Context Variants in melanocortin 4 receptor (MC4R) pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known. Objective We compared the severity of obesity and cardiometabolic risk markers in children with MC4R pathway-related clinically reported genetic variants relative to children without these variants. Methods A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity. Results Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R-related variants, PCSK1 risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups (P = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A&gt;G risk allele relative to those with MC4R-related variant of uncertain significance (P = .047), negative genetic testing (P = .012), and those with non-MC4R related variants (P = .048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups. Conclusion Variants in the MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A&gt;G PCSK1 risk allele, which was associated with higher LDL-C levels.

AbstractObjectivesTo compare long‐term transplant outcomes (organ rejection and retransplant) of simultaneous liver/kidney transplant (SLK) versus isolated kidney transplant (IK) for patients with primary hyperoxaluria (PH).MethodsThe Rare Kidney Stone Consortium PH registry was queried to identify patients with PH who underwent SLK or IK from 1999 to 2021. Patient characteristics and long‐term transplant outcomes were abstracted and analyzed. Statistical comparisons were performed with Kaplan–Meier plots and Cox proportional hazards models.ResultsWe identified 250 patients with PH, of whom 35 received care at Mayo Clinic and underwent SLK or IK. Patients who underwent SLK as their index transplant had lower odds of kidney rejection than did those who underwent IK (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.08–0.99; p = .048). The immunoprotective effect of concomitant liver and kidney transplant appeared to enhance outcomes for patients with PH. Additionally, the odds of retransplant were significantly lower for patients who underwent SLK as their index transplant than for those who underwent IK (HR, 0.08; 95% CI, 0.02–0.42; p = .003). Of five patients who underwent IK and had maintained graft function for at least 5 years after transplant, three (60%) had documented vitamin B6 responsiveness.ConclusionsPatients with PH who underwent SLK had a lower risk of kidney rejection and retransplant than those who underwent IK. Accurate genetic assessment for vitamin B6 responsiveness may optimize IK allocation. Novel therapeutics, such as lumasiran, have been introduced as promising agents for the management of PH.