Minimal But Essential Doses of Immunosuppression: A More Realistic Approach to Improve Long-Term Outcomes for Pediatric Living-Donor Liver Transplantation

University of Cambridge
Transplantation (Impact Factor: 3.83). 04/2011; 91(7):808-10. DOI: 10.1097/TP.0b013e31820f07de
Source: PubMed
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    • "Hence, these cases would require careful attention. Liver fibrosis is another histopathological feature of liver disease, and has been reported to be a significant indicator of prognosis after LDLT [48]. In the present study, 2 of the 12 recipients showed marked fibrosis (pairs 3 and 6); both were treated with continuous steroid, but were separated into different groups. "
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    ABSTRACT: Along with the increasing need for living-donor liver transplantation (LDLT), the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts) of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH). The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038), demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001). Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.
    PLoS ONE 04/2014; 9(4):e93749. DOI:10.1371/journal.pone.0093749 · 3.23 Impact Factor
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    • "Recently, it was proposed that the same mechanisms exist for both types of transplant, consisting of a response of " donor and recipient cells, each to the other, causing reciprocal clonal exhaustion, followed by peripheral clonal deletion " [9]. In other words, reciprocal tolerance induction is the reason human leukocyte antigen matching is not essential for organ transplantation [8]. Today, the main goal of researchers in transplantation is to induce the type of specific unresponsiveness labeled " full tolerance " toward the donor. "
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    ABSTRACT: Transplanting a uterus has unique characteristics, since a successful outcome is represented only by the birth of a viable healthy child. For this reason, critical issues in this type of transplantation differ profoundly from those of other solid organs and, beside a functioning uterus, involve 3 additional steps. First, at the time of implantation, the quality of embryo is tested by specialized decidual cells surrounding the implanting embryo; such testing is aimed at allowing the development of a normal embryo. Second, from early gestation onward, blood supply to the uterus increases from 45 to 750mL per minute. Vascular anastomoses should support such a marked increase in blood flow. Third, full transformation of spiral arterioles in the placental bed is required to direct 75% of the uterine blood flow to the intervillous space. Unfortunately, no suitable animal model is available for experimentation. Three overarching ethical issues must be considered. Should organ transplant be conducted when it is not absolutely necessary as a life-saving or quality-of-life-saving measure? To what extent should medicine delimit its potential in spite of societal desires? Should society demand from medicine the application of whichever technology can be developed and, if so, to what extent?
    International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 07/2013; 123(2). DOI:10.1016/j.ijgo.2013.05.010 · 1.54 Impact Factor
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    ABSTRACT: To outline the rationale of powerful depleting induction therapy with alemtuzumab and minimal maintenance immunosuppression after organ transplantation. The original observations in principle have been confirmed by many independent centres. Follow-up of the 'prope tolerance' protocol has confirmed a low incidence of rejection, infection and post transplant lymphoproliferative disorder (PTLD). Especially, encouraging results were obtained in African-Americans. There were few side effects and the regimen was well tolerated by patients. Treg cells were observed in the circulation, which could be an important factor in the mechanisms of graft acceptance using a prope tolerance regimen. There was a considerable reduction in the costs of the transplantation procedure. It is suggested that this minimalisation of maintenance immunosuppression is the best therapy currently available that we can offer to our patients.
    Current opinion in organ transplantation 06/2011; 16(4):353-8. DOI:10.1097/MOT.0b013e328348b44c · 2.88 Impact Factor
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