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.
Highlights
Liver transplantation (LT) has been carried out worldwide for patients with end-stage liver failure [1]
living-donor liver transplantation (LDLT) provides a unique and valuable means of answering this question, because it allows us to compare the characteristics of hepatocyte samples from an originally identical liver, part of which continues to be viable and functional in the donor, and another part that has functioned in a young recipient for a number of years after transplantation
Patients We offered all of the LDLT patients being treated at our institution a chance to participate in this pilot study, and twelve pairs volunteered to take part
Summary
Liver transplantation (LT) has been carried out worldwide for patients with end-stage liver failure [1]. Since the supply of cadaveric liver grafts is far short of the number of patients awaiting transplantation, living-donor liver transplantation (LDLT) has emerged as a critical surgical option for the patients. Along with the increasing need for LDLT, the issue of organ shortage continues to extend worldwide and has become a serious problem. Ensuring that a transplanted organ has a potentially sufficient working life remains one of the most important issues associated with LDLT [8,9,10]. In this context, a fundamental question has arisen concerning the senescence (aging process) of organs that are transplanted from elderly donors into young recipients. LDLT provides a unique and valuable means of answering this question, because it allows us to compare the characteristics of hepatocyte samples from an originally identical liver, part of which continues to be viable and functional in the donor, and another part that has functioned in a young recipient for a number of years after transplantation
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