Expression of collagens type I and IV, osteonectin and transforming growth factor beta-1 (TGFβ1) in biliary atresia and paucity of intrahepatic bile ducts during infancy

Background/Aims: Biliary atresia and paucity of intrahepatic bile ducts are the main causes of neonatal cholestasis leading to hepatic fibrosis. Fibrotic evolution is slow in paucity of bile ducts as compared to the rapid progression to biliary cirrhosis in biliary atresia when cholestasis persists despite hepatoportoenterostomy. Our aim was to compare the expression of collagens type I and IV, α-smooth muscle actin, osteonectin and transforming growth factor β1 in biliary atresia and paucity of bile ducts. Methods: Liver biopsies were obtained in 12 children with biliary atresia and in five with paucity of bile ducts. Collagens type I and IV, α-smooth muscle actin were detected with immunostaining. Collagens type I and IV, osteonectin and transforming growth factor β1 mRNAs were detected by in situ hybridization. Results: Expression of mRNA and proteins was roughly parallel. In ductular proliferation areas of biliary atresia: (1) the expression of collagens type I and IV and osteonectin was increased, and was localized to periductular myofibroblasts; (2) transforming growth factor β1 was expressed around biliary ductules, probably in inflammatory cells, and also in biliary cells. Osteonectin expression was also increased in the lobules. In paucity of bile ducts, there was no overexpression of collagens type I and IV and transforming growth factor β1, except in the only child with marked fibrosis. However, osteonectin expression was enhanced at the periphery of the lobules, even when fibrosis was mild or absent. Conclusions: These findings suggest that in biliary atresia ductular proliferation areas are the site of a marked production of extracellular matrix proteins in periductular myofibroblasts, probably secondary to transforming growth factor β1 production by inflammatory cells and by biliary cells. The weak expression of transforming growth factor β1 could explain the slow progression of fibrosis in paucity of bile ducts.