Pediatric liver transplantation for metabolic diseases: a single-center experience

Inborn errors of metabolism (IEM) are rare enzymatic disorders that often result in severe multiorgan dysfunction and death in pediatric patients. While advances in medical therapy of IEM have improved considerably, pediatric liver transplantation (pLT) has become an established treatment for many metabolic conditions. This study aims to compare the prognosis of patients with and without IEM indications after pLT.

A mixed retrospective and prospective cohort study of 330 pediatric patients who underwent pLT from 2003 to 2025 was performed. Patients were categorized into IEM and non-IEM cohorts, with the IEM group further stratified by indication into two subgroups: pLT indicated for primary progressive liver disease (IEM-LD) or for neuroprotection (IEM-NP). Clinical characteristics, perioperative variables, complications, and long-term outcomes were compared between groups, with additional analyses by cholestatic phenotype. Survival was assessed using Kaplan-Meier (KM) methods and compared using the log-rank test, and longitudinal outcomes were evaluated using generalized estimating equations.

Of 330 pLT recipients, 117 (35%) had IEM and 213 (65%) had non-IEM indications. IEM recipients had significantly fewer post-transplant vascular complications than non-IEM recipients and experienced shorter hospital stays (P = 0.016) and improved long-term patient (P = 0.040) and graft survival (P = 0.030). There were no differences in biliary complications, rejection episodes, cytomegalovirus (CMV) or Epstein Barr virus (EBV) disease, or post-transplant lymphoproliferative diseases (PTLD) between groups. Reduced-size grafts were used more frequently in IEM recipients (P < 0.002), whereas living-donor grafts were more common in non-IEM recipients (P < 0.003). Long-term metabolic and renal outcomes, including BMI, obesity, insulin use, and renal function, were similar between groups. Within the IEM cohort, IEM-NP recipients had improved patient survival (P = 0.020) compared with IEM-LD, with no difference in graft survival. IEM-NP recipients demonstrated reduced dependence on restrictive diets and disease-specific medications.

Liver transplantation has become an effective intervention strategy for many IEMs that are refractory to conventional non-surgical management. This progress has been facilitated by advances in surgical techniques, immunosuppression, close collaboration between transplant and metabolic disease teams, and innovative organ sourcing. Our findings further support pLT as a cornerstone therapy for IEM patients. Ongoing assessment of optimal timing, technical strategies, and follow-up after pLT may further improve patients' prognoses and quality of life.