Expression of FAS protein [CD95] and fas ligand in liver tissue of patients with HCV-induced chronic liver disease and its correlation with the disease progression

This study evaluated hepatic expression of both Fas and Fas ligand [FasL] in patients with hepatitis c virus [HCV]-induced chronic liver disease and its correlation with the histopathological activity and laboratory parameters as an early predictor of advancement of the disease. The selected patients were [39] males and [21] females, their ages ranged from [20-67years] with a mean of 43.5 +/- 4.5 years, as well as [10] subjects [normal individuals] serving as a control group. They were [7] males and [3] females, their age ranged from [26-53 years] with a mean of 39.5 +/- 7.3 years. Patients were grouped as [1] Chronic hepatitis [CH] group including [30] patients with chronic viral hepatitis C. [2] Liver cirrhosis [LC] group including [30] patients with post hepatitis C cirrhosis. Liver biopsy was done for all subjects using an automated 18-gauge true cut needle. Sections were stained with Haematoxylin and Eosin for histopathological diagnosis and with Maisson and Trichrome for assessment of fibrosis. Unstained paraffin sections from each case were subjected for immuno-histochemical procedures using indirect immunoflourescence technique for detection of apoptotic hepatic and lymphocytic cells using monoclonal antibodies. Semiquantitative analysis of the pattern and distribution of the Fas antigen and Fas Ligand as indicators for hepatic apoptosis was studied and assessed

Portal tract lymph and blood vessels changes in human chronic viral hepatitis, schistosomiasis and hepatocellular carcinoma; immunohistochemical and morphometric study

Study of morphometric changes occurring in hepatic blood and lymph vessels in different chronic liver lesions with portal hypertension including viral hepatitis [B and C], Schistosomiasis and hepatocellular carcinoma [HCC] on top of cirrhosis, and to find the relationship of these changes to liver fibrosis, portal hypertension and HCC, using a combination of immunohistochemical and computer-based methodology. After clinco-pathoilogical evaluation of human patients with chronic hepatic lesion associated with portal hypertension, the chronic vital hepatitis C [n = 19], B and C [n = 12], Schistosomiasis [n = 10] and HCC on top of cirrhosis [n = 9] and 10 non-hepatic patients as control have been studied. Morphometric assessment of the number and area of blood vessels and lymphatics as well as the percentage of hepatic fibrosis per tissue section, all were done using computer soft-ware [KS 400] on image analysis system and using a combination of immuno-histochemical computer-based methodology. Immuno-histochernical staining of blood vessels, for factor VIII and portal lymphatic for a smooth muscle actin were done using monoclonal antibodies. Hepatic fibrosis was stained by sirius-red. Portal tract area and the relative fibrosis per liver tissue section were significantly increased with increasing grade of hepatitis activity in the non malignant groups compared to the control cases, with high significance in Schistosomiasis hut in HCC insignificant fibrosis compared to other disease and to control groups. There was a significant increase in the number of blood vessels per portal tract in the disease groups, highly significant in Schistosomiasis and HCC compared to the control cases but the percent of blood vessel area was significantly reduced in HCC than Schistosomiasis. This angiogenic change was directly proportional with grades of hepatitis activity and esophageal varices as it was significant with grade III activity and histological grade of HCC. There was significant increase in the number of lymphatic vessels per portal tract in all diseased groups with highest significance in Schistosomiasis group compared to the control group. There was insignificant increase in number and significant increases of area of lymphatics in HCC. This lymphangiogenesis change was directly proportional with grades of hepatitis activity but insignificant in all groups of patients. The advancement of hepatic fibrosis and portal hypertension in chronic liver disease including Schistosomiasis and viral hepatitis [B and C] was associated with significant increase in the number of both portal blood and lymphatic vessels. There was highly significant increase in the surface area of lymphatic vessels in Schistosomiasis. There was marked angiogenesis in HCC. Further study of these factors could be a target for further work

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

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