Ductular Reaction and the K7-19 Progenitor Cell Sequence in Vascular Liver Disease: A New Perspective to Pathogenetic Mechanisms of Injury and Repair

Abstract

Background:Ductular reaction (DR), a process intricately connected with hepatocyte progenitor cells (HPCs) at the canal of Hering evokes considerable scientific interest. The present study was undertaken to (a) identify DR patterns in different subsets of hepatic vascular disease, (b) localize intermediate hepatobiliary progenitors activated in response to stresses to vascular flow while studying their K7/19 immunoexpression profiles, and (c) possibly provide new insights to pathogenesis. Methods: Forty-six cases of hepatic vasculopathy including Budd-Chiari syndrome [BCS] (11), acute hemorrhagic necrosis [AHN] (6), veno-occlusive disease [VOD] (7), non-cirrhotic portal fibrosis [NCPF] (10), extrahepatic portal vein obstruction [EHPVO] (10) and chronic venous congestion [CVC] (2) were randomly selected. Mean DR was scored as 1: 2–5, 2: 6–8, 3 > 8 after counting ductules per portal tract (D/ PT) separately on K7 and 19 immunostains. Extraportal ‘‘progenitors’’ were semiquantitatively graded as 0: None, 1: Occasional, 2: Significant number. This was done separately for hepatocytic and ductular cells on K7 & 19. Zonation effect, if any was noted. Results: DR, intermediate hepatocytic progenitors and extraportal ductules were seen in 69.5/45.6%, 84.7/30.4% and 65.2/50% cases respectively on K7/ 19 stain. DR was seenmost frequently in the subset of AHN (100%) and least in EHPVO (40%). All cases of BCS, AHN and CVC showed intermediate K7+ hepatocytic cells. Extraportal ductular cells (K7+/K19 ) were most common in AHN (100%) and showed a distinct centrilobular pattern. Conclusions: Derangements in vascular flow trigger prominent ductular reaction in all subsets of hepatic vasculopathy barring EHPVO. Severe parenchymal loss as seen in AHN activates both biliary and hepatocytic intermediate cells possibly as a response to extensive parenchymal cell loss. Vascular liver diseases show heterogeneity in K7/19 expression profiles of extraportal progenitors across all subsets, emphasizing that as a group vasculopathies may be trickier to reverse. Timely diagnosis hence is paramount tominimize damage. Corresponding author Tel: +91 9718599073: Puja Sakhuja. E-mail: pujasak@gmail.com