NULL

NULL

NULL

NULL

NULL

NULL

NULL

NULL

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.

Objectives: Cytomegalovirus and Epstein-Barr virus remain leading causes of morbidity and mortality in the living-donor liver transplant population, particularly in pediatric patients. Herein we compare the incidence, timing, and risk factors for infection in this group. Materials and Methods: We performed a retrospective study of 344 consecutive pediatric patients 193 women (56.1%) who received livingdonor liver transplants at Kyoto University Hospital. Patients were followed-up for maximum 7.1 ± 3.6 years (range, 0.02-13.2 y) after surgery. Results: The mean age at the time of transplant was 3.95 ± 4.75 years (median, 1.38 y; range, 0.07-17.87 y). A total of 156 patients (45.2%) developed viral infections. Of those patients, 91 (26.5%) developed cytomegalovirus infection, and 93 (27%) developed Epstein-Barr virus. Cytomegalovirus developed at 39.3 ± 34.6 days, while Epstein-Barr virus developed 3.99 ± 3.67 years after transplant. Frequent rejection attacks (hazard ratio [HR],1.58; 95% confidence interval [CI]: 0.14-2.18; P = .006) were an independent predictor for postoperative cytomegalovirus infection, while preoperative cytomegalovirus seropositive results (HR, 1.76; 95% CI: 1.03-2.18; P = .038), short cold ischemia time (HR, 1.0; 95% CI: 0.99-1.0; P = .02), larger graft (HR, 1.3; 95% CI: 1.00-1.73; P = .047), and new cases compared to old cases (HR, 2.27; 95% CI: 1.14-4.52; P = .019) were independent predictors for postoperative Epstein-Barr virus infection. Conclusions: Extended surveillance of cyto - megalovirus and Epstein-Barr virus DNAemia is recommended for pediatric patients receiving livingdonor liver transplants, particularly infants who are at high risk, and especially those exposed to frequent attacks of rejection and those that receive larger grafts.