Expression of collagens type I and IV osteonectin and transforming growth factor beta-1 (TGF beta 1) 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. Fibro tic evolution is slow in paucity of bile ducts as compared to the rapid pro gression to biliary cirrhosis in biliary atresia when cholestasis persists despite hepatoportoenterostomy, Our aim was to compare the expression of co llagens type I and IV, alpha-smooth muscle actin, osteonectin and transform ing growth factor beta 1 in biliary atresia and paucity of bile ducts. Methods: Liver biopsies were obtained in 12 children with biliary atresia a nd in five with paucity of bile ducts. Collagens type I and IV alpha-smooth muscle actin were detected with immunostaining. Collagens type I and IV, o steonectin and transforming growth factor beta 1 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 typ e I and IV and osteonectin was increased, and was localized to periductular myofibroblasts; (2) transforming growth factor beta 1 was expressed around biliary ductules, probably in inflammatory cells, land also in biliary cel ls. Osteonectin expression was also increased in the lobules, In paucity of bile ducts, there was no overexpression of collagens type I and IV and tra nsforming growth factor beta 1, except in the only child with marked fibros is, However, osteonectin expression was enhanced at the periphery of the lo bules, even when fibrosis was mild or absent. Conclusions: These findings suggest that in biliary atresia ductular prolif eration areas are the site of a marked production of extracellular matrix p roteins in periductular myofibroblasts, probably secondary to transforming growth factor beta 1 production by inflammatory cells and by biliary cells. The weak expression of transforming growth factor beta 1 could explain the slow progression of fibrosis in paucity of bile ducts.