Title: Early steroids after paediatric liver transplantation protect against T-cell mediated rejection – results from the ChilSFree study
Source: Liver Transplantation 2023, Sep 5. [E–publication]
Date of publication: September 2023
Publication type: Article
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<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.
