Immunohistochemical Detection of Hepatic Progenitor Cells in Chronic Viral Hepatitis C and Hepatocellular Carcinoma

Background: The risk of hepatocellular carcinoma (HCC) development in chronic hepatitis C infection is increased in Egypt accounting for 40-50% of these hepatitis cases. However, the underlying mechanism is not well understood. Progenitor cells (oval cells) of the liver are activated by liver damage as that caused by virus infection resulting in its proliferation and differentiation into singular and/or ductular forms. Hepatic progenitor cells (HPCs) may be the target cells for carcinogenesis in HCC. Aim: The aim of this study was immuno-histochemical identification of hepatic progenitor cells in cases of chronic hepatitis C infection and cases of HCC on top of cirrhosis using antibody against CK19. In addition to studying the relation between their number and the severity of the disease and if they can participate in pathogenesis of HCC. The prognostic role of CK19 in different cases of HCC was studied also. Material and Methods: An immuno-histochemical study using monoclonal antibody for CK19 was performed on paraffin sections of 55 specimens of liver tissues including normal liver, chronic hepatitis C and HCC on top of cirrhosis, they were collected from Pathology Departments of Zagazig University Hospital and in Alahrar Hospital in the period between 2008-2010. The mean number of singular HPCs as well as the mean number of atypical ductular reaction were quantified and correlated with the severity of chronic hepatitis and HCC. Results: HPCs were not detected in normal liver controls. In chronic viral C hepatitis biopsies, the average number of detected singular HPCs ranged from 1 to 5/HPF with a mean of 2.8±1.28 and the average number of atypical reactive ductules ranged from 1.4 to 5.35/HPF with a mean of 4.0±1.35. In biopsies of HCC both singular HPCs and atypical reactive ductules were detected in the fibrous bands surrounding cirrhotic nodules adjacent to HCC and ranged from 4 to 8/HPF with a mean of 5.6±1.2 for singular HPCs and from 7 to 9/HPF with a mean of 7.0±1.37 for atypical ductular reaction. Highly significant correlation between the number of HPCs either as singular HPCs or as atypical ductular reaction and the grade of chronic hepatitis activity (/ 0.035, p=0.000008 respectively), the stage of fibrosis (p0.000001,p=0.000006 Correspondence to: Dr. Anan Fathi, The Department of Pathology, Faculty of Medicine, Zagazig University respectively) and the degree of steatosis (p=0.000024, p=0.000017 respectively) were found. The number of HPCs in cirrhosis adjacent to HCC was significantly higher than that of cirrhosis without tumor development (p0.04, 0.049). Statistically positive correlations were found between the mean count of HPCs/HPF and the mean count of atypical reactive ductules /HPF regarding the severity of the disease (p0.000001, p=0.000004, p=0.000021, p=0.000003). CK19 was expressed in malignant hepatocytes of 2/2 (100%) cases of poorly differentiated HCC. Conclusion: The positive correlation between the number of HPCs and the severity of chronic hepatitis indicates the possible role of these cells in the development of HCC. Positive CK19 staining in HCC indicates the presence of a subtype of HCC with biliary differentiation and suggests its HPC origin. CK19 can be considered as HCC prognostic marker as it was expressed in all poorly differentiated HCC.