title: Factors affecting operational tolerance after pediatric living-donor liver transplantation: impact of early post-transplant events and HLA match.
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.
authors: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. tkoshiba@port.kobe-u.ac.jp
authors: Hidenori
authors: H
authors: Ohe
authors: Kayo
authors: K
authors: Waki
authors: Mami
authors: M
authors: Yoshitomi
authors: Takeshi
authors: T
authors: Morimoto
authors: Hanaa
authors: H
authors: Nafady-Hego
authors: Naoki
authors: N
authors: Satoda
authors: Ying
authors: Y
authors: Li
authors: Xiangdong
authors: X
authors: Zhao
authors: Shimon
authors: S
authors: Sakaguchi
authors: Shinji
authors: S
authors: Uemoto
authors: G Alex
authors: GA
authors: Bishop
authors: Takaaki
authors: T
authors: Koshiba
mesh_terms: D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival; D006680:HLA Antigens / Q000737:chemistry*; D015235:HLA-B Antigens / Q000627:therapeutic use; D006801:Humans; D007107:Immune System; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D010290:Parents; D011237:Predictive Value of Tests; D012044:Regression Analysis; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens; D015235:HLA-B Antigens; D007166:Immunosuppressive Agents; D016559:Tacrolimus