Background and aim: Liver transplantation (LT) has become the most efficient treatment for pediatric end-stage liver disease. However, during long-term follow-up, fibrosis in the allograft could cause liver dysfunction, cirrhosis or even retransplantation, which jeopardize the overall survival rates. Whether low-dosage prednisone treatment is effective in ameliorating or even reversing allograft fibrosis in unclear. Here we explored the clinical effect of prednisone in treating allograft fibrosis in a prospective cohort study.
Method: We established a prospective allograft fibrosis after pediatric LT (AFPLT) cohort, in which all enrolled participants received liver biopsy and blood test. For patients whose liver pathology indicated mild to severe fibrosis (LAFSc ≥2), oral prednisone (4-8mg per day) was prescribed. Liver biopsy and blood test will be conducted 6-12 months after treatment to check the status of allograft fibrosis.
Results: A total of 550 pediatric LT recipients were enrolled into this study, in which the mean age is 60.7±32.4 months with an average 48.3±20.5 months after transplantation. Among them, 39 patients (Fibrosis Group) were detected with allograft fibrosis and received prednisone treatment. The mean age of participants in the Fibrosis Group is 74.9±33.1 months at treatment, with an average follow-up time of 57.4±23.4 months. After 12.9±5.1 months of prednisone treatment, allograft fibrosis and intrahepatic inflammation exhibited significant improvement, with average LAFSc score decreased from 2.875 to 0.849, S score from 1.882 to 0.314 and G score from 1.688 to 0.182 (all p<0.001). Pathological evaluation revealed reduction of inflammatory infiltration and collagen deposit in the portal areas. Liver function also exhibited improvement, with the average peripheral white blood cell increased from 6.92 to 8.37×109/L (p=0.084) and hemoglobin from 118.1 to 127.3 g/L (p<0.05). Mean Fibroscan decreased from 9.33 to 7.99 kPa (p=0.0183), as well as peripheral collagen IV level reduced from 65.8 to 42.9 ng/mL (p=0.0134). Although other index related with hepatic fibrosis like PIIINP, hyaluronic acid and FIB-4 also showed reduction after treatment, no statistical significance was found. Immunofluorescence analysis to biopsy samples indicated decreased amount of intrahepatic fibroblast, cytotoxic CD8+ T cells and CD4+ T cells, as well as peripheral CD4+FOXP3+ regulatory T cells. No glucose or lipid metabolic disorders were found during follow-up.
Conclusion: Low dosage of oral prednisone is safe and efficient to ameliorate and reverse allograft fibrosis after pediatric LT.