Dynamics of Allograft Fibrosis in Pediatric Liver Transplantation

Progressive liver allograft fibrosis (LAF) is well known to occur long term, as shown by its high prevalence in late posttransplant liver biopsies (LBs). To evaluate the influence of clinical variables and immunosuppression on LAF progression, LAF dynamic was assessed in 54 pediatric liver transplantation (LT) recipients at 6 months, 3 and 7 years post-LT, reviewing clinical, biochemical data and protocol LBs using METAVIR and the liver allograft fibrosis score, previously designed and validated specifically for LAF assessment. Scoring evaluations were correlated with fibrosis quantification by morphometric analysis. Progressive LAF was found in 74% of long-term patients, 70% of whom had unaltered liver enzymes. Deceased grafts showed more fibrosis than living-related grafts (p=0.0001). Portal fibrosis was observed in correlation with prolonged ischemia time, deceased grafts and lymphoproliferative disease (p=0.001, 0.006 and 0.012, respectively). Sinusoidal fibrosis was correlated with biliary complications (p=0.01). Centrilobular fibrosis was associated with vascular complications (p=0.044), positive autoantibodies (p=0.017) and high gamma-globulins levels (p=0.028). Steroid therapy was not associated with reduced fibrosis (p=0.83). LAF could be viewed as a dynamic process with mostly progression along the time. Peri- and post-LT-associated factors may condition fibrosis development in a specific area of the liver parenchyma.