ANALYSIS OF PEDIATRIC LIVER ALLOGRAFT FIBROSIS BASED ON THE PARENCHYMAL AREAS

Previously we reported progressive liver allograft fibrosis in 74% (n=54) of long-term pediatric patients, connecting transplant-related parameters and clinical variables with portal, sinusoidal and centrilobular fibrosis. In this study, we extended the analysis to 595 protocol liver biopsies, which belonged to 139 pediatric liver transplant (LT) recipients followed at 6 months,1, 2, 3, 5, 7 and 10 years post- LT, correlating graft histology with clinical variables to endorse risk factors for fibrosis development. Normal liver histology was found in 5%, 3%, and 1 % of LB at 6 months, 3, and 5 years, respectively; nor at 7 years, neither at 10 years. Allograft fibrosis showed an increment of 44% between 6 months to 2 years, 54% between 3 to 5 years, and 33% in the long-term (7-10 years). The male gender (p=0.002); deceased donors (p=0.02); ischemia time> 400 minutes (p=0.03); biliary complications (p=0.03); gamma-globulins >15% (p=0.03); and lymphoproliferative disease (p=0.01) were found to contribute to fibrosis development. Whilst, no patients required re-LT a cause of fibrosis. Overall, sinusoidal fibrosis increased 68%, while portal and central fibrosis showed 50% and 13% of increment, respectively. Portal fibrosis was related to unspecific inflammation (p<0.01), and ductal proliferation (p<0.01). Sinusoidal fibrosis was also related to ductal proliferation (p=0.006). The steatosis found at early post-LT period (6 months to 2 years) was correlated with long-term sinusoidal and centrilobular fibrosis (p=0.03). The use of steroid therapy along the time (n=97) did not show to prevent fibrosis progression in our population, (p=0.1). In conclusion, we corroborate that liver allograft fibrosis has a dynamic evolution with mostly progression along the time. Peri- and post-LT-associated factors may condition fibrosis development in a specific area of the liver parenchyma.