Histological quantification of apha smooth muscle actin predicts future graft fibrosis in pediatric liver transplant recipients

Histological quantification of apha smooth muscle actin predicts future graft fibrosis in pediatric liver transplant recipients Varma S1, Stéphenne X1, Komuta M2, Bouzin.C3, Ambroise J4, Smets F1, Reding R5, and Sokal EM1 Université Catholique de Louvain, Cliniques Universitaires St Luc, 1Service de Gastroentérologie et Hépatologie Pédiatrique and Pediatric Research Unit, 2Service de Anatomopathologie, 3 Imaging Platform (2IP) Institut de Recherche Expérimentale et Clinique (IREC) , 4 Centre for Applied Molecular Technologies (CTMA), Institut de Recherche Expérimentale et Clinique (IREC) 5 Unités de Chirurgie Pédiatrique, Brussels, Belgium Aims: To evaluate significance of alpha smooth muscle actin (ASMA) expression on liver biopsy as predictor of future graft fibrosis in pediatric liver transplant (LT) recipients. Background: Activated hepatic stellate cells express cytoplasmic protein-alpha smooth muscle actin (ASMA) and subsequently secrete collagen leading to liver fibrosis. As activation of stellate cells precedes collagen deposition, we hypothesize that quantification of ASMA can predict the severity of future fibrosis. Patients: Stable pediatric LT recipients transplanted between 2006-20012, with two protocol biopsies less than two years apart and first being at more than 1year post LT. Patients with biliary, vascular complications, autoimmune hepatitis, hepatitis B or C infection, re-transplantation, or those with inadequate biopsy size were excluded. Methods: Metavir and liver allograft fibrosis scoring (LAFSc) used for fibrosis assessment. Automated staining for ASMA followed by digital quantification of ASMA positive area percentage was done. Fibrosis on initial biopsy specimen was labelled “current fibrosis” and on next biopsy labelled “prospective fibrosis”. The change between “current” and “prospective” fibrosis score was “prospective change in fibrosis”. Bile duct proliferation, lobular inflammation and portal tract infiltration was also evaluated. Results: 32 biopsy specimens, from 18 patients stained for ASMA and 56 evaluated for fibrosis. Significant association between the ASMA positive area percentage on initial biopsy and “prospective change in fibrosis” was seen; using Metavir (p-value = 0.02), LAFSc cumulative (p-value = 0.02) and LAFSc-portal (p-value=0.01) scores. AUROC analysis suggested ASMA positive area percentage > 1.05 to predict increased fibrosis on the next biopsy (60.0 % sensitivity, 90.0 % specificity). Conclusion: ASMA quantification on biopsy in liver transplant recipients predicts the future course of fibrosis, specifically portal fibrosis.