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

Transpl Int. 2012 Jan;25(1):97-106. doi: 10.1111/j.1432-2277.2011.01389.x. Epub 2011 Nov 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Separation
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Flow Cytometry
  • Graft Survival
  • HLA Antigens / chemistry*
  • HLA-B Antigens / therapeutic use
  • Humans
  • Immune System
  • Immune Tolerance*
  • Immunosuppressive Agents / therapeutic use
  • Liver Transplantation / methods*
  • Living Donors
  • Male
  • Parents
  • Predictive Value of Tests
  • Regression Analysis
  • Tacrolimus / therapeutic use
  • Transplantation, Homologous

Substances

  • HLA Antigens
  • HLA-B Antigens
  • Immunosuppressive Agents
  • Tacrolimus