Background/purpose: Connective tissue growth factor (CTGF) has been implicated in the pathogenesis of hepatic fibrosis and is elevated in the serum of children with biliary atresia (BA). The objective of this study was to evaluate hepatic CTGF messenger RNA (mRNA) expression and its relationship to hepatic histology in children with BA.
Methods: Connective tissue growth factor mRNA expression was evaluated by in situ hybridization in 26 liver biopsies from 11 patients with BA, 11 with other diseases, and 4 autopsy controls. Serial sections were immunostained with cell-specific markers to characterize the cells expressing CTGF. Biopsies were scored for CTGF expression (0-4) and inflammation and fibrosis (1-4).
Results: High levels of CTGF expression were observed in 9 of 11 BA with localization to biliary epithelial cells and vascular endothelial cells. Connective tissue growth factor mRNA expression was correlated with fibrosis in BA and all livers. In the 11 patients with other liver diseases, 7 had CTGF expression limited to hepatic stellate cells and vascular endothelial cells. None of the 4 livers in children without liver disease had significant levels of CTGF.
Conclusions: In BA livers, novel biliary epithelia CTGF mRNA expression is high and correlates with severity of fibrosis. These data support a role for biliary epithelial cell signaling in fibrogenesis.
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