Factors affecting operational tolerance after pediatric living‐donor liver transplantation: impact of early post‐transplant events and HLA match *

Summary Pediatric recipients of living‐donor liver transplants (LDLT) can often discontinue immunosuppression (IS). We examined factors affecting development of operational tolerance (OT), defined as off IS for >1 year, in this population. A historic cohort analysis was conducted in 134 pediatric primary semi‐allogeneic LDLT. Multivariate logistic regression analysis was used. The frequency of peripheral regulatory T cells (Tregs) was determined at >10 years post‐Tx by FACS analysis. IS was successfully discontinued in 84 tolerant patients (Gr‐tol), but not in 50 intolerant patients (Gr‐intol). The Gr‐intol consisted of 24 patients with rejection (Gr‐rej) and 26 with fibrosis of grafts (Gr‐fib). The absence of early rejection [odds ratio (OR) 2.79, 95% CI 1.11–7.02, P  = 0.03], was a positive independent predictor, whereas HLA‐A mismatch (0.18, 0.03–0.91, P  = 0.04) was a negative predictor. HLA‐DR mismatches did not affect OT. The Treg frequency was significantly decreased in Gr‐intol (4.9%) compared with Gr‐tol (7.6%) ( P  = 0.003). There were increased levels of tacrolimus in the first week in Gr‐Tol ( P  = 0.02). Although HLA‐B mismatch (8.73, 1.09–70.0, P  = 0.04) was a positive independent predictor of OT, its clinical significance remains doubtful. In this large cohort of pediatric LDLT recipients, absence of early rejection, HLA‐A match and the later predominance of Tregs are factors associated with OT.