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  • Title: Factors affecting operational tolerance after pediatric living-donor liver transplantation: impact of early post-transplant events and HLA match.
    Author: Ohe H, Waki K, Yoshitomi M, Morimoto T, Nafady-Hego H, Satoda N, Li Y, Zhao X, Sakaguchi S, Uemoto S, Bishop GA, Koshiba T.
    Journal: Transpl Int; 2012 Jan; 25(1):97-106. PubMed ID: 22117557.
    Abstract:
    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.
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