Ductal plates in hepatic ductular reactions. Hypothesis and implications. II. Ontogenic liver growth in childhood

Abstract

This article discusses the processes of bile duct growth and new lobule formation in the liver during childhood in the light of the ductal plate (DP) hypothesis. Unlike in other organs in which tubular elongation and branching ends with the creation of the organ-specific terminal differentiation products, in the liver a steadily enlarging parenchymal mass needs to establish continuity of its canalicular network with the existing bile duct system. The hypothesis suggests that this occurs by DP formation, like in the embryonic liver, and further assumes that pathological ductular reactions (DRs) induced by cholestasis or hypoxia are amplified equivalents of similar mechanisms operating at low level during liver growth. The concept is confronted with data on porcine liver growth, since swine and non-swine liver growth is thought to be comparable. Relative bile acid load may be the driving force for establishment of new canaliculo-ductular connections, supported in zones of relative hypoxia by hypoxia-inducible factor 1 alpha secreted by hepatocytes. The latter mechanism is at the base for induction of appropriate vascular changes in selected sinusoids, resulting in the development of portal inlet venules and additional draining central veins. The process gives rise to the formation of new single lobules by formation of new portal tracts or to the transformation of single lobules in compound lobules by development of new vascular septa. The concept of postnatal DP formation is important in the elucidation of several unexplained findings in adult liver diseases.

Recovery of Mature Hepatocytic Phenotype following Bile Ductular Transdifferentiation of Rat Hepatocytes in Vitro

“…5 This type of ductular reaction has been recently described and interpreted as a result of dedifferentiation of mature hepatocytes due to hypoxia. 6 It is important to precisely understand the origin and pathogenesis of the atypical ductular reaction because the prevention of its progression should be beneficial to maintain the proper functioning of the liver if the reaction is due to ductular metaplasia of hepatocytes.…”

Ductal plates in hepatic ductular reactions. Hypothesis and implications. III. Implications for liver pathology

“…The first paper discusses the three classical types of DR and adds DR induced by hypoxia as a fourth type [1]. The second paper postulates a role for postnatal DRs in DP configuration during normal liver growth in childhood [2]. The present manuscript considers the implications of the new observation and its interpretation for a number of pathological conditions in the liver, explaining some hitherto less elucidated aspects of several hepatic diseases.…”

“…This manuscript completes two papers about ductular reactions (DRs) in the liver, with critical review of current concepts, new observations, and hypothesis [1,2]. The new observation is that all DRs-except type 1 that corresponds to multiplication of pre-existing cholangiocytes-occur in ductal plate (DP) configuration.…”

“…The hypothesis on postnatal bile duct and lobule development [2] explains the morphology of VMCs as a postnatal malformation of DPs, and their general location in the more peripheral areas of liver parenchyma. VMCs in paraportal localization may correspond to malformations of some ductal plates involved in new portal tract development during postnatal life.…”

Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic and Biliary Differentiation in Cirrhotic Human Liver

“…[5][6][7][8][9][10][11][12][13][14] At the histological level, cirrhotic livers display a diversity of parenchymal cell morphology, including small and large hepatocytes, as well as, additional epithelial cell types in ductular or periductular areas. [15][16][17][18][19][20][21] Some of these cells may include adult stem/progenitor cell populations. The canals of Herring in periductular areas have been identified as a source of progenitor cells in adult human liver.…”