Late-Onset Graft Failure in Pediatric Liver Transplant Recipients: Implications of Acute-on-Chronic Liver Failure on Retransplantation Outcomes

As short-term outcomes following pediatric liver transplantation improve, an increasing burden of morbidity arises from chronic graft dysfunction warranting retransplantation. In this single-center retrospective cohort study, we aim to describe outcomes and determine factors that influence morbidity and mortality following liver retransplantation in pediatric recipients.

Data were collected on patient, and surgical factors which may influence survival and morbidity in all recipients < 18 years of age undergoing liver retransplantation between 2010 and 2024. Retransplants within 21 days were defined as early retransplants. For late retransplants, medical records were additionally reviewed to identify cases transplanted with acute decompensation of liver disease with organ failures. These cases were classified according to EASL-CLIF criteria for acute-on-chronic liver failure (ACLF).

Forty-four children underwent 52 retransplants with six third grafts and two fourth grafts. Sixteen were early retransplants with 9 (56.33%) due to vascular complications and the remaining primary non-function. Thirty-six were late retransplants with 13 (36.1%) due to chronic rejection and 13 (36.1%) due to biliary complications. Eight (22.2%) late retransplants fulfilled ACLF criteria. Patient survival for all retransplants at 1-, 5- and 10-year was 75% (95% CI: 64.1%-87.7%), 69.1% (95% CI: 57.6%-82.9%), 64.8% (95% CI: 51.9%-80.9%) and graft survival was 70.0% (95% CI: 58%-85.3%), 57% (95% CI: 43%-74.4%), 46% (95% CI: 32%-68.5%) respectively with no significant difference in survival for early versus late retransplants. Factors significantly associated with reduced retransplant survival for late retransplants were preoperative renal replacement therapy (HR: 3.80, 95% CI: 1.09-13.28, p = 0.04), meeting criteria for ACLF (HR: 3.08, 95% CI: 1.14-8.31, p = 0.03), and prolonged warm ischemia time (HR: 1.24, 95% CI: 1.09-1.67, p = 0.04). No significant perioperative factors reducing posttransplant survival were identified for early retransplants.

Children with chronic graft dysfunction are at risk of ACLF which is associated with significant increased posttransplant mortality. Improved disease models are needed for patients with chronic graft dysfunction to better inform decision-making regarding the timing of retransplantation.