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Is there any immunological advantage to living‐related donor liver transplantation in pediatric recipients?

Living-related liver transplantation (LRLT) was first carried out in 1989 (1) and has an important role in clinical practice. The development of LRLT and split-liver transplantation has reduced the pressure on waiting lists for cadaveric organs, particularly for children. There is now considerable evidence of both shortand long-term success with LRLT, which may be related to the ability to carry out the procedure electively, to assess the donor organ carefully, and to limit the ischaemic time (2–4). Tokoyi et al., in the August 2002 issue of Pediatric Transplantation, addressed the question of whether LRLT organs have an immunologic advantage over cadaveric transplants. They carried out a retrospective study to look specifically at the incidence of rejection following transplantation of 51 patients with a cadaveric graft and 37 with an LRLT graft. There was no difference in patient or graft survival, and no difference in the incidence of rejection, in the first year between the two groups. There was, however, a significant reduction in the incidence of rejection in the LRLT group after 1 yr posttransplant, and reduction of immunosuppression was more successful in this group. These findings are consistent with the results of Takatsuki et al. (4); they selected LRLT recipients, who had been stable for 2 yr post-transplant (without any rejection in the second year) and successfully weaned up to 38% of these patients off all immunosuppression. In addition, other studies have confirmed that there was no difference in acute rejection (5, 6), but a significant reduction in chronic rejection, in patients with LRLT compared to cadaveric grafts (4% vs. 16%) (7). In the study by Tokoyi et al., protocol biopsies were performed at 7 days, 14 days and 1 yr posttransplant, as well as biopsies performed for clinical indications. It is not clear from the data provided whether all grades of rejection were included or treated. It is clearly recognized that some episodes of acute rejection resolve spontaneously without the need for additional therapy, and that the long-term prognosis may even be improved for these patients (8). It is also not clear whether the severity of the rejection episodes in the two groups were comparable or clinically significant. It is possible that some episodes of early rejection may be associated with tolerance, as has been demonstrated in an animal model, in which there was a T-cell infiltrate in both rejection and tolerance (9). It may be that the T-cell infiltrate described as early rejection in some patients of the LRLT group may have been a beneficial engagement between the organ and the recipient immune system leading to graft tolerance. If some of the LRLT group have subsequently developed tolerance this could explain why there was a discrepancy between the incidence of early and late rejection in the two groups. There are a number of other factors that may play a role in the development of rejection in these two groups, and some of these have been addressed. Of particular note is the difference in age of the donors and recipients between the groups. The donors in the LRLT group were all adults, and the recipients in this group were younger than those in the cadaveric group. Both of these factors may influence the development of rejection. It is recognized that the immune system of neonates is different from that of adults, and that younger recipients have improved graft acceptance (10). One mechanism for this appears to be a different balance between T helper subsets (11). T-cell responses can be categorized into those which are involved in aggressive cellmediated type responses, producing interferon-c (Th1), and those associated with less aggressive Pediatr Transplantation 2002: 6: 364–366