Study of the factors influencing the progression of allograft fibrosis in the long-term follow-up of pediatric liver transplant récipients : impact of the immunosuppressive therapy and role of Hepatic Stellate Cells

The present PhD proposes a rigorous evaluation and quantification of pediatric liver allograft fibrosis in 595 liver biopsies of 139 patients from 6 months to 10 years following liver transplantation, analyzing the influence of clinical variables and the immunosuppression on fibrosis progression, as well as the relevance of activated Hepatic Stellate cells (HSCs) in predicting allograft fibrosis development. A novel fibrosis scoring system, the Liver Allograft Fibrosis Score, was designed and validated specifically for allograft fibrosis assessment, categorizing separately sinusoidal, centrilobular and portal fibrosis. Progressive fibrosis was found in 74% of the liver biopsies reviewed. Clinical factors were identified to promote fibrosis in a specific area of the liver parenchyma. The steroid therapy did not contribute to reduce fibrosis. Finally, the high proportion of activated-HSCs found in this population was useful as a predictor of long-term allograft fibrosis development.