Relevance of activated hepatic stellate cells in predicting the development of pediatric liver allograft fibrosis.

Activated hepatic stellate cells (HSCs) are the main collagen-producing cells in liver fibrogenesis. With the purpose to analyze their presence and relevance in predicting liver allograft fibrosis development, 162 liver biopsies of 54 pediatric liver transplant (LT) recipients were assessed at 6 months, 3 and 7 years post-LT. METHODS: The proportion of activated HSCs, identified by α-smooth muscle actin (ASMA) immunostaining and the amount of fibrosis, identified by PicroSirious-red staining (PSR%), were determined by computer-based morphometric analysis. Fibrosis was also staged by using the semiquantitative liver allograft fibrosis score (LAFSc), specifically designed to score fibrosis in the pediatric LT population. RESULTS: Liver allograft fibrosis displayed progression along the time by PSR%, (p< 0.001) and by LAFSc, (p< 0.001). The ASMA expression decreased in the long-term, with inverse evolution respect to fibrosis (p< 0.01). Patients with ASMA-positive HSCs area ≥ 8% at 6 months (n=20) developed higher fibrosis proportion compared to those with ASMA-positive HSCs area ≤ 8% (n=34) at the same period of time and in the long-term (p= 0.03 and p<0.01, respectively), but not at 3 years (p= 0.8). ASMA expression ≥ 8% at 6 months, was found as independent risk factor for 7 years-fibrosis development by PSR% (r2 =0.5, p< 0.01) and by LAFSc (r2 =0.3, p= 0.03). Further, ASMA expression ≥ 8% at 3 years showed association with the development of fibrosis at 7 years (p= 0.02). CONCLUSION: There is a high proportion of activated HSCs in pediatric LT recipients. ASMA ≥ 8% at 6 months seems to be a risk factor for early and long-term fibrosis development. In addition, Activated HSCs showed inverse evolution respect to fibrosis in the long-term. This article is protected by copyright. All rights reserved