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Expansion of Hepatic Progenitor Cell Population in Liver Fibrosis of Elderly Cadavers
Author(s) -
Chiu Sophia,
Mak Ki M.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.740.8
Subject(s) - pathology , population , lobules of liver , fibrosis , cirrhosis , hepatic stellate cell , biology , cytokeratin , medicine , immunohistochemistry , environmental health
Human hepatic progenitor cells (HPC) normally reside in a quiescent state in the canals of Hering located at the interface between the portal tract and the periportal parenchyma of the liver lobule. In chronic liver disease such as alcoholic liver disease, nonalcoholic fatty liver disease, viral hepatitis, chronic cholestasis, hereditary liver disorders, and neoplasia, HPC become activated and proliferate. Being bipotential progenitors, HPC can differentiate into cholangiocytes or hepatocytes. Expansion of HPC population in the periportal parenchyma, which constitutes the HPC compartment, is termed ductular reaction or HPC response. Preliminary studies revealed ductular reaction associated with liver fibrosis of elderly cadavers with diverse causes of death (FASEB 2016; 30:1044.4; 1044.5) . The present study assessed fibrosis‐associated HPC expansion in progressive stages of fibrosis of the aged liver. Paraffin liver sections of embalmed cadavers were immunoperoxidase stained using monoclonal cytokeratin 7 (CK7) antibody. Sections were post‐stained with Sirius red stain for assessment of fibrosis. HPC are small oval‐shaped cells containing an ovoid nucleus and scant cytoplasm that stained positively for CK7, a phenotypic marker of HPC. In livers with minimal fibrotic changes, CK7 + HPC lined the canals of Hering, formed reactive ductules in the form of anastomotic strings of cuboidal cells in the periportal HPC compartment, and presented as isolated cells in the liver parenchyma at variable distance from the portal tract. In septal fibrosis, in addition to the abovementioned lobular distribution, CK7 + HPC were observed at the septal‐parenchymal border of developing septa and bridging septa, and around perisinusoidal fibrotic lesions. Counts of HPC from 11 liver samples in each stage of fibrosis showed that the number of cells per HPC compartment increased from 7.93 ± 1.32 in minimum fibrosis to 17.18 ± 2.96 ( P = 0.01) in septal fibrosis, and 21.83 ± 3.69 ( P = 0.002) in bridging fibrosis. In the mid‐pericentral lobular areas, HPC counts increased from 2.72 ± 0.96 cells/field in minimum fibrosis to 6.92 ± 1.39 cells/field ( P = 0.02) in septal fibrosis, and 11.15 ± 1.99 cells/field ( P = 0.001) in bridging fibrosis. Conclusions Expansion of HPC population in the periportal HPC compartment in advanced stages of fibrosis represents a HPC response to liver fibrogenesis. Increased intralobular distribution of HPC likely resulted from periportal to lobular parenchyma migration, possibly relating to hepatic regeneration consequent to liver injury caused by fibrosis. Elderly cadavers provide a valuable source of liver specimens for assessing HPC expansion associated with liver fibrosis progression in the aged liver.