Immunohistochemical detection of fas expression and Bcl2 in liver tissues of patients with chronic liver disease

ABSTRACT

Apoptosis is a type of cell death that occurs in chronic hepatitis. It has been suggested to be mediated through Fas antigen. Bcl[2] gene is involved in the regulation of programmed cell death by providing a survival advantage to rapidly proliferating cells. This work aims to study Fas expression [as apoptotic marker] and Bcl, in different chronic liver disease and to correlate-these findings with the etiological causes, severity of the disease and with the progress of the pathology. This study was carried on 77 cases with chronic liver diseases and 5 control cases. Patients were admitted diagnosed and managed in Tropical Medicine Department in El Zahraa University Hospital. All cases were subjected to full history taking, full clinical examination and laboratory investigation in the form of complete blood picture, liver function tests, kidney function tests, hepatitis markers upper gastrointestinal endoscopy, sigmoidoscopy and abdominal ultrasonography. Liver biopsy was taken and examined histopathologically also for the presence of expression of Fas and BcL[2]. Patients were classified into 4 groups I pure schistosamal infection, group II pure chronic hepatitis C infection, group III mixed schistosomal and viral hepatitis, and group IV hepatocellular carcinoma. Our results showed Fas expression in the GI, II, III, IV in [50% +/- 2.5, 72% +/- 3.2, 85% +/- 4.8, 35.2 +/- 3.2] at the hepatocytes while the expression at the Kupifer cells were [35.2 +/- 11.2, 60.4 +/- 12.2, 65.4 +/- 10, 83 +/- 2.2]. On the other hand, it was expressed at the portal tracts in [25.2 +/- 8, 50.1 +/- 5.2, 60.2 +/- 2.4, 15.4 +/- 2] in the studied groups respectively. This expression increased significantly in all liver tissues of chronic liver diseases when compared with the control group and it was markedly elevated at the Gill [group of mixed infection] also it is increased with the severity of disease either the necro-inflammatory activity or the fibrosis staging. While the Bcl[2] expression was found to be-increased at the malignant tissues [502 +/- 4.2] than other lesions [20.2 +/- 2.4, 35.5 +/- 4.5, 40.8 +/- 2.7] also in cirrhotic patients than the non-cirrhotic patients. There was significant increased difference between the groups and the group of control, this expression also correlated with the presence of Fas expression significantly [r=0.333, p<0.01]. Also Bcl[2], expression was found to be significantly increased with the necroinfiammatory state, fibrosis staging and also with the malignant differentiation. So, from these results, we concluded that apoptosis plays an important role in the pathogenesis of chronic liver disease either due to chronic hepatitis C virus infection, schistosomiasis and malignancy. Process of apoptosis may be related to immune mediated system and active inflammation of the liver. This may explain the high Fas expression in cases of mixed schistosomiasis and chronic hepatitis C infection. Also the antiapoptotic regulator Bcl2 may contribute to viral persistence and progression of liver disease in chronic hepatitis C. As well this expression may be used as a prognostic indicators of hepatocellular carcinoma in cirrhotic and hepatitis patients