Early steroids after paediatric liver transplantation protect against T-cell mediated rejection –results from the ChilSFree study

Goldschmidt, I; Chichelnitskiy, E; Götz, J; Rübsamen, N; Karch, A; Jäger, V; Kelly, D; Lloyd, C; Debray, D; Girard, M; D'Antiga, L; Di Giorgio, A; Hierro, L; Pawlowska, J; Klaudel-Dreszler, M; McLin, V; Korff, S; Falk, C; Baumann, U

Abstract

Background: Steroid-free immunosuppression protocols gained popularity in paediatric liver transplantation (pLT) after the introduction of Interleukin-2-receptor blockade for induction therapy. We analyzed clinical and immunological outcome data of the multicenter prospective observational ChilSFree study in order to compare impact of steroid-free vs. steroid-containing immunosuppressive therapy following pLT in a real-life scenario. Results: 246 children (55.3\% male, age at pLT median 2.4 (range 0.2-17.9) years) transplanted for biliary atresia (43\%), metabolic liver disease (9\%), acute liver failure (4\%), hepatoblastoma (9\%) and other chronic end-stage liver diseases (39\%) underwent immune monitoring and clinical data documentation over the first year after pLT. Patient and graft survival at one year were 98.0\% and 92.7\% respectively. Primary immunosuppression was basiliximab induction followed by either tacrolimus (Tac) monotherapy (55\%), Tac plus steroid tapering over three months (29\%), or cyclosporine and steroid tapering (7\%). One centre used intra-operative steroids instead of basiliximab followed by Tac plus mycophenolate mofetil (MMF) (7\% of patients). N=124 biopsy-proven T-cell-mediated rejections (TCMR) were documented in n=82 (33.3\%) patients. TCMR occurred early (median 41 days, range 3-366 days) after pLT. Patients initially treated with Tac+steroids experienced significantly fewer episodes of rejection than patients treated with Tac alone (chi square p {\textless}0.01). Use of steroids was associated with earlier down-regulation of pro-inflammatory cytokines IFN-γ, IL-6, CXCL8, IL-7, IL-12p70. Both primary immunosuppression with Tac+steroids and living related liver transplantation (LDLT) were independent predictors of rejection-free survival one year after pLT on logistic regression analysis. Conclusion: Adjunctive steroid therapy after pLT leads to earlier suppression of the post-pLT pro-inflammatory response and significantly reduced rejection rates during the first year after pLT (15.9\%). 65\% of patients initially treated without steroids remain steroid free over the first 12 months without rejection.