Bile ductule formation in fetal, neonatal, and infant livers compared with extrahepatic biliary atresia

Abstract

antigen, carcinoembryonic antigen, and epithelial membrane The cell of origin of intrahepatic bile ducts during fetal antigen. [13][14][15][16][17][18][19][20][21][22][23] These studies have further supported the hepadevelopment remains a subject of controversy, although tocytogenic theory. there has been recent evidence that they form from heCytokeratins are the intermediate filaments of the cypatocytes. However, the origin of neoductules and ducts toskeleton characteristic of epithelial cells. [24][25][26][27] At least 20 in the setting of liver disease has not been extensively CKs have been distinguished on the basis of different molecuinvestigated in humans. Using anticytokeratins characlar weights and isoelectric points on two-dimensional gels. 24-26 teristic of hepatocytes and bile ducts, we repeated ear-The human embryonic liver is composed of liver cell precurlier studies of fetal development to compare ductule forsors (hepatoblasts) in its earliest developmental stages. mation in normal developing and newborn livers withThese hepatoblasts express cytokeratins 8, 18, and 19. 19 At the ductules formed during extrahepatic biliary atresia. We utilized an antibody to proliferating cell nuclear an-approximately the eighth week of gestation, the hepatoblasts tigen (PCNA) staining to determine which cells were in that are adjacent to the mesenchyme surrounding the largest active DNA synthesis (S phase) during fetal development hilar portal veins become more immunoreactive for cytokeraand liver disease progression. The results indicated that tins 8, 18, and 19. These cells, which surround the portal hepatocytes undergo a phenotypic switch (metaplasia) vein branches, become smaller and later flatten to form the to form ductular cells during fetal development. There ductal plate. 1 They become more immunoreactive to the CK was no ductular cell replication in the fetal livers. In antibodies, while the hepatoblasts away from the mesencontrast, both bile ductular metaplasia and proliferation chyme start to lose their antigenicity for cytokeratin 19, and were observed in biliary atresia. Therefore, both a lim-by 10 weeks of gestation, the future parenchymal cells are iting plate phenotypic switch to ductules and replication antigenic for only cytokeratins 8 and 18, as seen in adult of ductular cells play a role in the increase in the duct-liver parenchymal cells. ules seen in the progression to biliary cirrhosis. Bile duc-The ductal plate later becomes a double cell layer, and a tular proliferation in biliary atresia, however, was less slitlike opening begins to form between the cell layers to form than that seen in hepatocytes, whereas the number of lumens. The formation of these ductal plates starts at the bile ductules increased and the relative proportion of hilum where the largest portal vein branches are located, hepatocytes diminished as the accompanying periductu-and then progresses to the smaller portal tracts away from lar fibrosis progressed to cirrhosis. (HEPATOLOGY 1996; the hilum. At 20 weeks of gestati...

Development of the Intrahepatic Biliary Tree

“…26 By 20 weeks of gestation, immunoreactivity for CK-7 appears in epithelial cells of developing ducts near the hilum, and this progresses to the periphery. 27 Immunoreactivity for CK-7 increases through term and reaches the adult level at 1 month after birth. Thus, normal adult hepatocytes express only CK-8 and -18, whereas intrahepatic bile ducts express CK-7 and -19 (reviewed in Cocjin et al 27 ).…”

“…27 Immunoreactivity for CK-7 increases through term and reaches the adult level at 1 month after birth. Thus, normal adult hepatocytes express only CK-8 and -18, whereas intrahepatic bile ducts express CK-7 and -19 (reviewed in Cocjin et al 27 ). Faa et al 28 demonstrated that CK-20 in the rat may represent a late maturation marker for the fetal biliary tract because it appears in bile duct epithelium 1 day prior to parturition.…”

Mechanisms of Alcoholic Liver Injury

“…In this phenomenon, liver cells undergo a phenotypic switch to form ductules in the limiting plate of hepatocytes at the periportal zone during the development of cirrhosis (18). The stellate cells located next to the switched hepatocytes proliferate to provide stroma for the newly formed ductules in a process that recapitulates bile duct formation in the fetal liver (53). This is a self-perpetuating interaction that leads to progressive fibrosis and cirrhosis due to growth factors released by the ductules (acidic fibroblast growth factor), which stimulates stellate proliferation, and HGF and stem cell factor released by the stellate cells, which stimulates bile ductule proliferation (54,55).…”

The Pathology of Cholestasis

“…Indeed, EHBA and neonatal hepatitis with giant cell transformation have been thought to represent points on a continuum of manifestations of the same disorder. [101][102][103] Lobular changes should not be allowed to distract attention from the portal tract features. 104 The accuracy of percutaneous liver biopsy in the diagnosis of EHBA is reported as 60 to 95%, ''depending on the skill of the pathologist.''…”