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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.

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Despite living-donor liver transplant being a life-saving therapy for patients with hepatitis B virus with or without hepatocellular carcinoma, outcomes for patients with these diseases are worse. Hepatitis B virus recurrence or relapse of hepatocellular carcinoma can result in subsequent graft loss or patient death. In this study, we discuss the postoperative outcomes of patients with hepatitis B virus infection after living-donor liver transplant.We retrospectively analyzed 125 patients with hepatitis B virus-related end-stage liver disease, comparing results with 1228 control patients who had other pathologies, including hepatitis C virus, combined hepatitis B virus and hepatitis C virus, and neither virus.Survival rates of patients with hepatitis B virus did not differ from the control groups (P >.05). Patients with concurrent hepatitis B virus and hepatocellular carcinoma were significantly older (P .0001), had critical status (P .0001), had chronic underlying pathology (P =.001), lower graft-to-recipient body weight ratio (P =.047), needed more intraoperative plasma transfusion, and experienced more rejection episodes than those without hepatocellular carcinoma. Of interest, in 5 patients who had hepatitis B virus recurrence after living-donor liver transplant, Model for End-Stage Liver Disease score was significantly higher than those who did not have recurrence (P =.015). In addition, 2 patients had hepatocellular carcinoma recurrence in the form of peritoneal metastasis, with both patients having high preoperative alpha-fetoprotein levels.Our study provides details on long-term outcomes of patients with hepatitis B virus infection who had undergone living-donor liver transplant. Based on our results, we suggest that prolonged antiviral prophylactic therapy in the form of hepatitis B immunoglobulin with either lamivudine or entecavir be considered for patients who associated with risk factors to prevent postoperative recurrence.

Loss of cell surface expression of CD127 on CD4+ CD25++ regulatory T-cells (Tregs) may be a useful marker to efficiently isolate Tregs. As FOXP3 was specifically used to identify Tregs, combining these two markers could give better identification for patient with operational tolerance (OT) after liver transplantation. To testify this mixed lymphocyte reaction (MLR), the function of circulating CD4+ CD25++ CD127dim cells (CD127dim cells) was examined in immunosuppression (IS)-free pediatric recipients after liver transplantation (LTx) (group operational tolerance: OT) (Gr-tol n = 25) compared to recipients who could not stop IS due to clinically overt rejection (group intolerance) (Gr-intol n = 18), recipients who were weaning IS (Gr-weaning n = 11) and age-matched healthy volunteers (Gr-vol n = 11). In addition, the frequencies of CD127dim cells vs CD4+ CD25++ CD127dimFOXP3+ (CD127dimFOXP3+) cells were compared in these four groups by FACS analyses. Our results showed that The proliferation of CD4 cells to donor antigens was reduced compared to third-party antigens only in Gr-tol (P = 0.022) but not in other groups (P = NS). Depletion of CD127dim cells resulted in a donor antigen-specific abrogation of this MLR hyporesponsiveness in Gr-tol (P 0.001) but not other groups (P = NS). This implied that CD127 efficiently isolated donor antigen-specific Tregs. The frequencies of CD127dim cells were significantly lower in Gr-intol (5.2% ± 1.9%) compared to those in Gr-tol (7.8% ± 1.8%) (P 0.001) as were the frequencies of CD127dim FOXP3+ cells (Gr-tol: 5.4% ± 1.7% vs Gr-intol: 2.9% ± 1.0%, P 0.001). Of interest, there were fewer CD127dimFOXP3+ cells in Gr-intol (2.9% ± 1%) than in Gr-weaning (5.1% ± 1.8%) (P = 0.002), but no difference in CD127dim cells (Gr-intol: 5.2% ± 1.9% vs Gr-weaning: 6.7% ± 2.0%) (NS). Thus, combining FOXP3 with CD127 for phenotype analysis demonstrated an unequivocal difference between Gr-intol and Gr-weaning that was not detected by CD127 alone. In conclusion CD127 was a useful surface marker to isolate donor-antigen-specific-Tregs in OT after LTx. The additive effect of its combination with FOXP3 is important in phenotypical Treg analyses of OT patients.

Background: Diabetes has a deleterious effect on bone. Ginger has been used in a wide variety of diseases. This study was designed to clarify changes of the bone of streptozotocin induced diabetic adult male rats and the possible role of ginger in preventing these changes. Methods: Thirty adult male rats were used. They were divided into three groups: Group I: control group. Group II: Diabetic group, diabetes was induced in rats by single intrapertonial injection of freshly streptozotocin 60 mg /kg body weight. Group III: diabetic rat treated with ginger (500 mg /kg) orally for 6 weeks. The serum levels of glucose, insulin, calcium, phosphorus, alkaline phosphatase and osteocalcin (OC) were measured. Both femora of each rat were processed for histological, immunohistochemical and morphometrical studies. Results: STZ-induced diabetes was characterized by significant increase in serum glucose and alkaline phosphatase levels and significant decrease in serum insulin, calcium, phosphorus and OC levels as well as significant decrease in number of osteoblasts and osteopontin (OPN) protein expression in the femur bone. Also, histological results showed degeneration of osteoblasts and osteocytes, multiple osteoporotic cavities, decreased collagen fibers and irregularity of bone surfaces Treatment of diabetic rats with ginger resulted in significant decrease in serum glucose and alkaline phosphatase levels and significant increase in serum insulin, calcium, phosphorus and OC levels as well as significant increase in number of osteoblasts and OPN protein expression in the femur bone and improvement of histological results. Conclusion: Diabetes could lead to increased incidence of bone loss. Ginger could ameliorate diabetic changes of bone and may represent a promising agent for treating of diabetic osteoporosis.