The role of oval cells in chronic hepatitis type B and type C. A clinicopathologic study

A.C. Tsamandas; E.S. Felekouras; Stavroula Salakou; Th. Kourelis; K. Tepetes; D.S. Bonikos; E. Papalampros; G.K. Michalopoulos

Authors A.C. Tsamandas, E.S. Felekouras, Stavroula Salakou, Th. Kourelis, K. Tepetes, D.S. Bonikos, E. Papalampros, G.K. Michalopoulos.

Abstract

Aim: Oval hepatocytes, (OC) as a part of liver stem cells, are involved in the progress of liver disease and hepatocellular carcinoma (HCC) development, in experimental models. This study investigates the presence and possible role of OC in chronic hepatitis (CH) type B and C in humans.

Design: The study comprised 50 needle liver biopsies with CH and 50 wedge/needle normal liver biopsies as controls. CH cases included 29 HBV (all HBSAg+-14HbcAg+), and 21 HCV (PCR+) instances. HAI ranged from 3/18-15/18, and the architectural stage from 1 to 6 (6HBV/8HCV). Epidemiologic and laboratory data were obtained from medical records. The streptavidin-biotine technique was employed on paraffin sections using antibodies for cytokeratin 19 (CK19), glutathione-S-transferase-Ã° (GST-Ã°) and leukocyte common antigen (LCA). Cells with microscopic features of OC that were CK19 (+), or GST-Ã° (+) and LCA (-) were scored. Oval cell percentage was expressed following morphometric analysis, and the results were correlated with clinical parameters, grade and stage of CH.

Results: Oval cells were present in all 50 liver biopsies with CH but in 0/50 controls. They were located in periportal areas; occasionally formation of small ducts was recorded. Oval cells were also recognized more often in association with fibrous bands and accompanied inflammatory infiltrates. The CK19+ cells varied from 20-90% and GST-Ã°+ cells from 20-75%, of the total oval cells numbers. The percentage of CK19+ and GST-Ã°+ cells were directly correlated with i) categories A, B, and D of Ishak score (p<0.01), ii) total Ishak score (p<0.01), iii) architectural grade (p<0.01), iv) transaminases values (p<0.05). Direct correlation was also seen between CK19 (+) and GST-Ã°(+) cells (p<0.05).

Conclusions: Presence of oval hepatocytes is a common finding in liver biopsies from patients with CH type B or C. The significant association between oval cell percentage and severity of disease (HAI grade and stage) implies that OC proliferation is related to progress of liver disease and/or increased risk for hepatocellular carcinoma development.

Keywords: oval cell, chronic hepatitis, carcinogenesis, fibrosis