Analysis of clinical variables associated with tolerance in pediatric liver transplant recipients

Abstract

Tolerance has been defined as stable graft function off IMS. We reviewed the data of 369 pediatric liver transplant patients to examine demographic differences that may have a PV of pediatric LT tolerance. Of the 369 patients, 280 patients were stable with detectable blood levels of IMS agents and with good graft function without biopsy proven REJ > 1 yr posttransplantation, 18 patients were noted to be TOL off IMS, 27 patients were taking MIS with drug levels below detectable range by standard laboratory parameters, and 44 patients developed one or more episodes of biopsy proven acute or chronic REJ > 1 yr post-transplantation. Variables, including percentage of biliary atresia, type of transplanted organ, history of EBV infection, patient and donor gender, and ABO blood type mismatch between recipient and donor did not have PV of tolerance. Average age in years was 1.37 ± 1.53 (0.3-4.9) for TOL, 1.14 ± 0.89 (0.4-3.1) for MIS and 3.35 ± 4.45 (0.3-16) for REJ. Age difference of TOL/MIS vs. REJ was significant (p =0.002) and TOL vs. REJ was significant (0.01). Age at the time of transplantation is an important predictor in the development of pediatric LT tolerance.

Epstein‐Barr virus DNA monitoring in serum and whole blood in pediatric liver transplant recipients who do or do not discontinue immunosuppressive therapy

“…Identification of operational tolerance is essential to avoid negative side effects of IS and may serve to reduce the risk of PTLD to a minimum . In our material, there were no cases of PTLD.…”

“…These so‐called chronic high‐load carriers, although often asymptomatic, are at potential risk of developing PTLD . As yet, there are no reliable markers to predict PTLD in these patients, and minimization of IS has become standard of care to reduce the risk for PTLD and other EBV‐related complications . It has been shown that IS can be completely withdrawn in up to 25% of liver recipients without causing rejection, which might reflect unique tolerogenic properties of the liver or that a lower immunological reactivity in the liver is necessary because of the great exposure to antigens brought to the liver via the portal vein .…”

What is the long-term outcome of the liver allograft?

“…The majority of studies have been carried out on patients with stable graft function, usually at least 2 years post-transplant, with overall success rates in the region of 10-20% (reviewed by Demetris [23] and Sanchez-Fueyo [159]). A higher frequency of successful weaning of immunosuppression has been observed in the paediatric population [160], particularly in young children [161], possibly reflecting the immature immune system in children. Pre-weaning biopsies are mainly used to exclude the presence of rejection, but may also be able to identify other features that are predictive of tolerance -examples include the absence of significant portal inflammation [19], lack of lobular CD3+ and CD8+ T cells [19], lack of fibrosis (in HCV-positive patients [20]), and the presence of portal T cells with a regulatory phenotype (FoxP3-positive) [21,162].…”

Operational tolerance: Past lessons and future prospects

“…Only the Pittsburgh and Kyoto groups have a large enough prospective experience in children, succeeding in achieving tolerance in 22 (34%) and 49 (43%) recipients, respectively 54, 55. Favorable factors for success include longer time from transplantation, achievement of monotherapy, transplantation for nonimmune diseases, the presence of LPD, and younger age 72, 73. Of unclear importance is the presence of fibrosis and decreased bile duct size on postwithdrawal protocol biopsies of “operationally tolerant” pediatric recipients 60.…”