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

Exp Clin Transplant. 2020 Jun;18(3):325-333. doi: 10.6002/ect.2019.0387. Epub 2020 Apr 7.

Abstract

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.

MeSH terms

  • Age Factors
  • Antilymphocyte Serum / adverse effects
  • Antilymphocyte Serum / therapeutic use*
  • Child
  • Child, Preschool
  • Female
  • Graft Rejection / drug therapy*
  • Graft Rejection / immunology
  • Graft Rejection / mortality
  • Graft Rejection / pathology
  • Graft Survival / drug effects*
  • Humans
  • Immunity, Cellular / drug effects*
  • Immunophenotyping
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Infant
  • Liver Transplantation / adverse effects*
  • Liver Transplantation / mortality
  • Male
  • Phenotype
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Factors
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Time Factors
  • Treatment Outcome

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents