Ductal plates in hepatic ductular reactions. Hypothesis and implications. I. Types of ductular reaction reconsidered

Abstract

This article focuses on the observation that most hepatic ductular reactions (DRs) have ductal plate (DP)-like patterns. Considering old and recent data, it hypothesizes that in DR, dedifferentiation of hepatocytes in ductular metaplasia may lead to the de novo development of liver stem/progenitor cells (LPCs). The three recognized types of DR are reconsidered, and an additional fourth type, DR type 2B, is added. In DR type 1 whose pattern differs from DP, the pre-existing cholangiocytes multiply and adjust the ductal structure in response to micro-environmental changes induced by oedema and inflammation. This DR fails to establish new canaliculo-ductular connections. DRs types 2A, 2B and 3 represent progenitor cell-based reactions in DP configuration which establish canaliculo-ductular connections similar to DPs in embryonic and foetal liver development. DR type 2A occurs in periportal areas in chronic cholestatic and inflammatory diseases and is interpreted as a reaction of LPCs, which either pre-exist or derive from dedifferentiated hepatocytes. DR type 2B occurs in centrolobular areas and zones of parenchymal hypoxia, is induced by hypoxia and corresponds to "ductular metaplasia" like type 2A with a presumably similar cellular origin. DR type 3 relates to the well-recognized activation of LPCs that reside in the canals of Hering. All DRs in DP configuration play a role in progression of fibrosis in chronic liver diseases.