LAUSR

Introduction Clinical operational tolerance can be achieved after liver transplantation in some proportion of selected patients. We have tried to reduce immunosuppression (IS) of the stable out-patient pediatric liver transplant recipients. In this cross-sectional study, we analyzed the status of IS, the histological findings of the liver biopsy, and serological donor specific HLA antibodies (DSA) in the long-term pediatric liver transplant recipients. We confirmed operational tolerance in the aspect of pathology and serology. Method 862 cases of liver transplants were performed for the pediatric patients under 20 years old until 2013 in our institution. 537 cases, who visited our outpatient clinic within 5years were involved in this study. The patients were divided into 4 groups; Operational Tolerance group (OT), who were completely free from IS; Weaning group (Weaning), who took IS less frequently than daily IS; Calcineurin inhibitor alone group (CNI), who took CNI alone, tacrolimus or cyclosporine; and Multiple IS Drugs group (MD), who took more than two kinds of IS drugs such as CNI, antimetabolites, and steroids. 479 cases underwent liver biopsy during this period. Pathological findings were diagnosed by the specialized pathologists, and fibrosis was scored by METVIR system. DSA were examined in 355 cases by solid-phase assay by a Luminex analyzer. Result The numbers of OT, Weaning, CNI, and MD cases were 59, 19, 287, and 172, respectively. The median years after operation were 21.7 in OT, 17.8 in Weaning, 14.9 in CNI, and 13.6 in MD, respectively. (p<0.001) There were no significant differences among these groups in the age at operation, gender, and ABO incompatibilities. The reasons of cessation of IS were elective weaning in 32 patients, side effects of IS in 18 patients, and non-adherence in 3 patients. The fibrosis scores of OT were significantly lower than those of the other groups. (P<0.001) Only 5 of 44 OT cases showed progressive fibrosis (bridging fibrosis), while 131 of 436 in the other groups showed progressive fibrosis; 5 of 18 in Weaning group, 58 of 256 in CNI, and 68 of 162 in MD. (p=0.0045) The frequencies of DSA were also 5 of 25 in OT group and 135 of 344 in the others; 4 of 12 in weaning, 73 of 192 in CNI, and 58 of 140 in MD (p=0.0431) There was significant correlation between DSA and fibrosis progression in CNI and MD, while no correlation in OT and Weaning. Conclusion This cross-sectional study revealed that a proportion of pediatric recipients achieved operational tolerance in clinical, histological, and serological aspects. 5 IS-free patients with DSA did not show progressive fibrosis.