P9.34: Application of Mesenchymal Stem Cells for the Treatment of Liver Graft Dysfunction Caused by Chronic Rejection. Case Report

Abstract

Background: Development of immunosuppressive therapy (IST) complications after liver transplantation (LT) requires its minimization. Decrease of immunosuppression in the long-term period after transplantation in 8% of patients is accompanied with the development of chronic rejection (CR). Objective: The aim of this report was to demonstrate the successful treatment of liver transplant CR with mesenchymal stem cells (MSCs) in patient with acute kidney injury (AKI) and IST minimizing. Results: Patient with unresectable liver alveococcosis underwent LT. After surgery patient received a three-component IST, which after six months was de-escalated to tacrolimus monotherapy (Tac). A year after the operation graft dysfunction developed, which was accompanied by a maximum increase of AST up to 511 U/l and ALT up to 507 U/l, GGTP up to 1753 U/l and ALP up to 474 U/l. IST was escalated: pulse therapy with glucocorticosteroids was performed twice; mycophenolate mofetil, mTOR inhibitors, intravenous immunoglobulin were added. Thrice performed puncture liver biopsy demonstrated the chronicity of the alloimmune conflict. Developed AKI in the process of anti-rejection therapy required decreasing of Tac, which led to increase of cytolysis and cholestasis. Infusion of allogeneic MSCs with a total dose of 8 x 106 cells per kg led to normalization of laboratory blood tests. The Tac concentration was 0.8 ng/ml; kidney function recovered: urea level was 7.1 mmol/l, creatinine - 80 µmol/l, GFR - 25 ml/min. Application of MSCs formed immunotolerance: the suppressor subpopulation of T-regulatory CD3+CD4+CD25highCD127- lymphocytes increased and effector CD3+CD8+naïve T-lymphocytes, antigen-presenting myeloid dendritic cells, and antibodies-producing CD19+ naïve B-lymphocytes decreased. Conclusions: MSCs can be used in CR as an effective alternative IST that can replace the immunosuppressive effect of basic immunosuppressants.