Association of posttransplant donor-specific HLA antibody with liver fibrosis after pediatric liver transplantation

Abstract

Introduction: Although the short-term outcomes of pediatric liver transplantation (LT) have improved, the long-term outcomes, which are especially important in pediatric LT, have not improved to the same extent. This is partly caused by immunological progression of liver graft fibrosis. However, liver function test results are commonly normal even among patients with liver fibrosis; therefore, the indication and timing of liver graft biopsy have not been established. The aim of this study was to evaluate the significance of posttransplant donor-specific antibody (DSA) as a predictor of liver fibrosis during long-term follow-up after pediatric LT. Method: A retrospective analysis of liver graft fibrosis was performed in 34 LT recipients. Patients were divided into two groups based on histological findings, and clinical characteristics among patients with immunological graft fibrosis were assessed. The fibrosis group included patients with fibrosis of F2 or more. Result: Of the 34 patients included in this study, 11 (32%) were included in the fibrosis group and 23 in the non-fibrosis group. No significant between-group differences were found regarding pretransplant characteristics, including age, sex, ABO incompatibility, and immunosuppressive regimen. Episodes of biopsy-proven acute rejection and non-adherence to immunosuppressive drugs were comparable between the two groups. The mean fluorescence intensity (MFI) for anti-DR donor-specific antibodies was significantly higher among the patients with immunological fibrosis than among those without (1655 vs. 389; p = 0.009), and significantly more patients tested positive in the fibrosis group than in the non-fibrosis group (73% vs. 30%; p = 0.03). Conclusion: Posttransplant development of anti-DR DSA is a risk factor of liver fibrosis during long-term follow-up. This finding provides useful information for the implementation of valid histological examinations of liver grafts for patients with higher MFI, especially for anti-DR DSA, after pediatric LT.