Early steroids after pediatric liver transplantation protect against T-cell-mediated rejection: Results from the ChilSFree study.

Steroid-free immunosuppression protocols gained popularity in pediatric liver transplantation (pLT) after the introduction of IL-2-receptor blockade for induction therapy. We analyzed the clinical and immunologic outcome data of the multicenter prospective observational ChilSFree study to compare the impact of steroid-free versus steroid-containing immunosuppressive therapy following pLT in a real-life scenario. Two hundred forty-six children [55.3% male, age at pLT median: 2.4 (range: 0.2-17.9) y] 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 1 year was 98.0% and 92.7%, respectively. Primary immunosuppression was basiliximab induction followed by tacrolimus (Tac) monotherapy (55%), Tac plus steroid tapering over 3 months (29%), or cyclosporine and steroid tapering (7%). One center used intraoperative steroids instead of basiliximab followed by Tac plus mycophenolate mofetil (7% of patients). N = 124 biopsy-proven T-cell-mediated rejections were documented in n = 82 (33.3%) patients. T-cell-mediated rejection occurred early (median: 41 d, range: 3-366 d) after pLT. Patients initially treated with Tac plus steroids experienced significantly fewer episodes of rejection than patients treated with Tac alone (chi-square p <0.01). The use of steroids was associated with earlier downregulation of proinflammatory cytokines interferon (IFN)-γ, Interleukin (IL)-6, CX motif chemokin ligand (CXCL)8, IL-7, and IL-12p70. Both primary immunosuppression with Tac plus steroids and living donor liver transplantation were independent predictors of rejection-free survival 1 year after pLT on logistic regression analysis. Adjunctive steroid therapy after pLT leads to earlier suppression of the post-pLT proinflammatory response and significantly reduced rejection rates during the first year after pLT (15.9%). Fifty-one percent of patients initially treated without steroids remain steroid-free over the first 12 months without rejection.

Autopsy versus clinical findings in patients with systemic sclerosis in a case series from patients of the EUSTAR database.

OBJECTIVES: Subclinical organ pathology occurs regularly in systemic sclerosis (SSc) and affects correct prognosis as well as treatment choices. We aimed to evaluate autopsy data for organ involvement with subsequent correlation to clinical data in order to assess discrepancies in pathological and clinical findings in SSc. METHODS: A standardised autopsy questionnaire from diseased patients registered in the European Scleroderma Trials and Research group (EUSTAR) cohort was analysed on cause of death and various manifestations in different organ systems. Clinical data obtained from the EUSTAR database of the corresponding patients including cause of death and disease manifestations of lung, heart, kidney, gastrointestinal, skin or musculoskeletal organ involvement were retrospectively analysed and compared to autopsy data. RESULTS: 11 patients (6 women, 5 male) aged between 23 and 84 were included. Cause of death defined by pathologist and clinician were identical in 9/11 cases. In 8 individuals, cause of death was related to heart and lung pathologies. Heart and lung involvement (both 10/11) were the most frequently detected organ involvement at autopsy. Here, myocardial fibrosis occurred in 66% and lung fibrosis in 50% of the patients. Clinically, diastolic function abnormalities (6/11), conduction block (4/11), reduced DCLO (6/11) and dyspnea (8/11) were the most prevalent cardiopulmonary findings. For heart and renal involvement we found higher prevalence in autopsy than by clinical diagnosis. Especially myocardial fibrosis and renal arteriosclerosis were only obtained by autopsy in several individuals. CONCLUSIONS: Clinical diagnostic procedures are limited in detection of end-organ damage, especially for cardiac involvement. All the more post mortem examinations are needed for quality verification of clinical diagnosis and might help as to better understand the disease processes as well as to improve patient care.