Efficacy of Antithymocyte Globulin Treatment for Severe Centrilobular Injury Following Pediatric Liver Transplant: Clinical Significance of Monitoring Lymphocyte Subset

OBJECTIVES Central perivenulitis can occur in association with T-cell-mediated rejection and can sometimes require strong immunosuppressant therapy as refractory rejection. Furthermore, patients with central perivenulitis are more likely to have subsequent episodes of T-cell-mediated rejection and develop chronic rejection than those without central perivenulitis. We retrospectively analyzed clinical data of pediatric patients with episodes of T-cell-mediated rejection according to severity of central perivenulitis and monitored HLA-DR-positive CD8-positive T cells and recent thymic emigrants during treatment for T-cell-mediated rejection. MATERIALS AND METHODS We identified biopsy-proven T-cell-mediated rejection in 50 liver transplant recipients (45 with living-related donors, 5 with deceased donors) between September 2014 and August 2018. Lymphocyte subsets in peripheral blood samples were analyzed. RESULTS Of 50 pediatric patients, 30 were boys and 20 were girls (median age at transplant of 1.1 y; interquartile range, 0.6-6.2 y). Central perivenulitis was found in 46 patients (92%), which was mild in 13, moderate in 16, and severe in 17. Antithymocyte globulin was more frequently administered to patients with severe central perivenulitis than others (P < .05). Patients with antithymocyte globulin treatment were less likely to have subsequent episodes of T-cell-mediated rejection than those without this treatment (P < .05). The absolute number of CD8-positive HLA-DR-positive T cells in patients during treatment was significantly higher than in control patients (P < .05). The absolute number of recent thymic emigrants in patients with active infection was significantly lower than in patients without infection (P < .05). CONCLUSIONS Our results suggest the efficacy and safety of antithymocyte globulin for treating T-cell-mediated rejection with severe central perivenulitis in pediatric liver transplant recipients and suggest that antithymocyte globulin can prevent subsequent episodes of T-cell-mediated rejection. Analyzing lymphocyte subsets during treatment for rejection may help highlight viable therapeutic strategies for achieving a good outcome.