Human Hepatic Progenitor Cell Expansion in Liver Fibrosis of Elderly Cadavers

Abstract

AIMS: Expansion of human hepatic progenitor cells (HPCs) is a key feature of liver fibrosis associated with a variety of chronic liver diseases. We studied HPC expansion and its relationship to canals of Hering (CoH) and ductular reaction (DR) in liver fibrosis progression of aged cadavers. METHODS: Thirty-five cadavers (83.8 ± 10.8 years) with minimal fibrosis, septal fibrosis, bridging fibrosis and incomplete cirrhosis were studied. Cytokertin 7 immunoperoxidase staining was used to highlight HPCs, CoH and DR. RESULTS: HPC counts in the periportal HPC compartment and in the mid-lobule and centrilobule were 2.3-2.7 times and 2.8-4.5 times higher in advanced fibrosis stages (septal fibrosis, bridging fibrosis and incomplete cirrhosis) compared to minimal fibrosis, respectively. Periportal CoH numbers and DR grades were 2.0-2.6 times and 2.6-2.7 times higher in advanced fibrosis than in minimal fibrosis, respectively. Both CoH numbers and DR grades significantly correlated with periportal HPC counts. There was also a significant correlation between CoH numbers and DR grades. Portal inflammation, but not lobular inflammation, was significant in bridging fibrosis. Steatosis was not an obvious feature associated with the HPC expansion. CONCLUSION: Increased periportal and lobular HPC counts reflect an expansion of HPCs with increased periportal to lobular HPC migration. The expansion likely represents a regenerative response to chronic liver injury in the elderly. Our findings also point to an intricate linkage between the HPCs, CoH and DR in hepatic fibrogenesis. Cadaveric livers provide a source of specimens for evaluating the role of HPCs in fibrosis progression of the aged liver.