Ductular reaction and putative progenitor cells (or 'progenitor cells'), which are presumed to be the human counterpart of the oval cells in rat liver, have been discerned in various human
liver diseases, including chronic viral
hepatitis. Since in experimental models of
chronic hepatitis the activation of oval cells is correlated with the inflammatory infiltrate, this study investigated whether there is a correlation in chronic viral
hepatitis between the number of 'progenitor cells' extending into the lobule and the severity of parenchymal
inflammation, on the one hand, and the extent of ductular reaction and the severity of interface
hepatitis, on the other hand. Liver biopsies of 55 patients with
chronic hepatitis B and/or C were used. The severity of parenchymal
inflammation and of interface
hepatitis was semiquantitatively graded on a haematoxylin and
eosin-stained
paraffin section, while the number of 'progenitor cells' and the extent of the ductular reaction were assessed on a serial section stained for
cytokeratin (CK) 7. In addition, more extensive phenotyping of 'progenitor cells' was performed on sections from frozen material from five patients, using
antibodies against CK7, CK8, CK18, CK19,
chromogranin-A, and the rat
oval cell marker OV-6. The number of more centrally located 'progenitor cells' correlated significantly with the severity of the parenchymal
inflammation, while the extent of the ductular reaction correlated significantly with the severity of interface
hepatitis. These findings suggest that in chronic viral
hepatitis,
inflammation plays a role in 'progenitor cell' activation and its topography. In cases with moderate and severe lobular
inflammation, 'progenitor cells' were strikingly scattered throughout the parenchyma and surrounded by intermediate hepatocyte-like cells, suggesting their migration into the parenchyma and their differentiation towards the hepatocytic lineage.