胆道閉鎖症

Biliary reconstruction is often considered the Achilles' heel of liver transplantation, yet risk factors and outcomes remain poorly defined, particularly in pediatric living donor liver transplantation (LDLT). This international multicenter study aims to identify predictors of biliary complications and evaluate their impact on long-term outcomes. 2,665 pediatric patients who underwent LDLT between January 2019 and December 2023 across 19 centers were included. Multivariable logistic regression was performed to identify risk factors, while time-dependent Cox models were used to assess impact on survival. The median recipient age was 11 months (IQR: 6.3-34.6) and biliary atresia was the most common diagnosis (59.7%). Bile leak and anastomotic stricture occurred in 3.6% (n=97) and 1.9% (n=51) of patients, respectively. For bile leak, higher donor BMI was an independent predictor (OR 1.09 per kg/m², 95% CI: 1.02-1.17). For anastomotic strictures, longer cold ischemia time was a significant predictor (OR 1.36 per hour, 95% CI: 1.03-1.79). Bile leak (aHR 4.39, 95% CI: 1.04-18.60) and biliary stricture (aHR 6.26, 95% CI: 1.58-24.80) were associated with worse graft survival. Patient survival was not significantly impacted by bile leak and stricture. Early complications more often required surgery, but survival and failure-to-rescue rates were similar regardless of treatment approach. Ultimately, bile leak and anastomotic stricture remain significant threats to graft survival. The identified risk factors offer insights for risk stratification and prevention strategies aimed at improving outcomes in children undergoing LDLT.

Ferroptosis is an iron-dependent regulatory cell death mechanism mediated by lipid peroxidation. Increasing evidence suggests that this process is closely related to the etiology of a variety of paediatric diseases. This review systematically elaborates the core molecular mechanism of ferroptosis, and highlights that newborns exhibit organ‑specific susceptibility to ferroptosis, predominantly attributed to the convergence of high PUFA content in the developing brain and erythrocytes, immature antioxidant defences, and a propensity for free iron accumulation. Building on this, we further examine the role of ferroptosis in multiple childhood disorders, such as bronchopulmonary dysplasia, hypoxic-ischaemic encephalopathy, haemolytic hyperbilirubinemia, necrotizing enterocolitis, retinopathy of prematurity, and neonatal rotavirus‑associated biliary atresia. Furthermore, we synthesize existing evidence, which is largely preclinical, regarding therapeutic interventions that modulate ferroptosis, including iron chelators, selective inhibitors (e.g., ferrostatin-1), and activators of endogenous antioxidant pathways (e.g., Nrf2 inducers). We also discuss the multiple difficulties and challenges encountered by the current study in paediatric clinical trials, especially with respect to ferroptosis‑related issues. This review identifies a series of key barriers to clinical translational research in paediatric ferroptosis, based on a systematic review of the available evidence. In response to these obstacles, we propose a prioritized translational framework that focuses on juvenile animal models, age-stratified pharmacokinetics, and patient-derived organoids, to provide guidance for translating clinical practice to this vulnerable population.

OBJECTIVES: Biliary atresia is a progressive cholangiopathy in neonates leading to liver failure and often requiring liver transplant. Although surgical interventions like the Kasai portoenterostomy offer temporary relief, the disease continues to be the leading cause of liver transplant. This study aimed to evaluate the demographic, clinical, and laboratory characteristics of these patients and the effects of these characteristics on outcomes. MATERIALS AND METHODS: This cohort study included 167 pediatric patients (aged <18 years ) with confirmed biliary atresia, selected from the Shiraz Pediatric Liver Cirrhosis Cohort Study between 2018 and March 2024. We analyzed data collected from the pediatric liver cirrhosis registry and assessed patient outcomes by comparing survivors versus those who did not survive. RESULTS: Among the 167 patients, 86 (51.5 % ) died and 81 (48.5 % ) survived. Those who died were significantly younger at enrollment (15.47 vs 36.31 months old ) and had higher internal normalized ratio, prolonged partial thromboplastin time, and elevated liver enzymes compared with survivors. The Kasai portoenterostomy was performed in 77.8 % of patients, with no significant difference in its distribution between survivors and patients who did not survive. CONCLUSIONS: Although most children had a Kasai surgery and over one - third had a liver transplant, a significant number did not survive. To improve outcomes for children with biliary atresia, better perioperative and postoperative care, aggressive treatment of liver dysfunction, and robust nutritional support are essential.

BACKGROUND: Cross-sectional tacrolimus concentrations and liver biochemistry may not reflect longitudinal instability after paediatric liver transplantation. AIMS: To derive a risk score based on pharmacokinetic and biochemical variability at one centre and validate it at an independent centre. METHODS: This retrospective two-centre landmark study included 93 recipients, predominantly infants with biliary atresia (83.9%) undergoing primary liver transplantation, the majority receiving living-donor grafts (88.2%), and 86 recipients in the validation cohort (76.7% biliary atresia; 45.3% living-donor). Variability in tacrolimus trough concentrations, aspartate aminotransferase and total bilirubin was calculated from measurements obtained 6-12 months after transplantation. Patients with major complications during this period were excluded. Follow-up began at 12 months. The primary outcome was the first major late complication or death without a preceding qualifying complication. A three-point score was derived and applied unchanged to the external cohort. RESULTS: Nineteen derivation-cohort patients and 12 validation-cohort patients experienced late events. The score assigned one point each for tacrolimus variability above 25%, aspartate aminotransferase variability above 50% and total bilirubin variability above 50%. Scores of 2-3 identified higher-risk patients in the derivation cohort, with a hazard ratio of 4.48, a 95% confidence interval of 1.79-11.17 and a concordance index of 0.748. Areas under the curve at 1, 3 and 5 years were 0.883, 0.802 and 0.740. In the external cohort, the hazard ratio was 8.90, with a 95% confidence interval of 2.66-29.81 and corresponding areas under the curve of 0.753, 0.775 and 0.789. CONCLUSIONS: Integrating the longitudinal variability of tacrolimus exposure and liver biochemistry provides a practical, externally validated, non-invasive tool for paediatric liver transplantation survivors.