Factors affecting operational tolerance after pediatric living-donor liver trans

[Clark]

http://onlinelibrary.wiley.com/doi/10.1111/j.1432-2277.2011.01389.x/abstract

Factors affecting operational tolerance after pediatric living-donor liver transplantation: impact of early post-transplant events and HLA match†
Hidenori Ohe1,§, Kayo Waki2,3, Mami Yos***omi1, Takeshi Morimoto4, Hanaa Nafady-Hego1,5, Naoki Satoda1, Ying Li1, Xiangdong Zhao1, Shimon Sakaguchi6, Shinji Uemoto1, G. Alex Bishop7, Takaaki Koshiba8
DOI: 10.1111/j.1432-2277.2011.01389.x
Transplant International
Early View (Online Version of Record published before inclusion in an issue)

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.