Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis occurs in the normal liver and in various forms of liver disease. The CD95 (APO-1/Fas) (CD95) receptor mediates apoptosis, and liver cells in animal models are acutely sensitive to apoptosis initiated by this receptor. We have used primary human hepatocytes as a model system to investigate CD95-mediated apoptotic liver damage. Treatment of fresh human hepatocytes with low concentrations of agonistic antibodies against CD95 resulted in apoptosis of > 95% of the cultured liver cells within 4 and 7.5 h. Immunohistology of a panel of explanted liver tissues revealed that hepatocytes in normal livers (n = 5) and in alcoholic cirrhosis (n = 13) expressed low constitutive levels of CD95. CD95 receptor expression was highly elevated in hepatocytes in hepatitis B virus-related cirrhosis (n = 9) and in acute liver failure (n = 8). By in situ hybridization CD95 ligand messenger RNA expression was absent in normal liver but detected at high levels in livers with ongoing liver damage. In cases of hepatitis B virus-related cirrhosis and acute hepatic failure, ligand expression was found primarily in areas with lymphocytic infiltration. In contrast, in patients with alcoholic liver damage, high CD95 ligand messenger RNA expression was found in hepatocytes. These findings suggest that liver destruction in hepatitis B may primarily involve killing of hepatocytes by T lymphocytes using the CD95 receptor-ligand system. In alcoholic liver damage, death of hepatocytes might occur by fratricide and paracrine or autocrine mechanisms mediated by the hepatocytes themselves.
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PMID:Involvement of the CD95 (APO-1/Fas) receptor and ligand in liver damage. 759 93

Hepatitis C virus (HCV) and hepatitis B virus (HBV) are major causative agents of chronic liver disease. However, the mechanisms responsible for liver cell injury remain to be clarified. Cytotoxic T lymphocytes play a crucial role in liver cell injury by HCV or HBV infection. Recently, perforin and Fas ligand have been shown to be the only molecules causing T cell-mediated cytotoxicity in short term assays. Therefore, we examined the implication of the Fas system-mediated apoptosis in the liver cell injury. When examined by immunohistochemical method, Fas antigen expression in chronic hepatitis C or B was upregulated in accordance with the severity of liver inflammation. Furthermore, Fas ligand expression was detected in liver-infiltrating mononuclear cells obtained from patients with chronic hepatitis C. These observations suggest that the Fas system plays a dominant role in liver cell injury by viral hepatitis.
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PMID:[Apoptosis in human diseases: role of Fas system in liver cell injury by viral hepatitis]. 917 Sep 76

Fas (APO-1/CD95)-mediated apoptosis plays an important role in liver cell destruction in viral hepatitis. Using sandwich ELISA, we measured serum levels of soluble Fas (sFas) in patients with hepatocellular carcinoma (HCC) who were positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibody. sFas levels were significantly higher in HCC patients (median 4.07 ng/ml; range 0.14-29.18 ng/ml) than levels in age-matched healthy donors (0.29 ng/ml; 0-4.90 ng/ ml) (P < 0.0001) and HBsAg or anti-HCV antibody-positive patients with liver cirrhosis (LC) (2.16 ng/ ml; 0.24-8.39 ng/ml) (P = 0.0015). An arbitrary cut-off level of 3.03 ng/ml (mean + 3 s.d. of controls) revealed the positive frequency of sFas in each group: 1.7% in healthy subjects, 25.9% in LC, and 59.0% in HCC (sensitivity 59.0% and specificity 74.1%). All HCC sera tested contained transmembrane-deleted sFas and some contained another sFas lacking the Fas C-terminal. The positive frequency of either sFas (59.0%) or alpha-fetoprotein (AFP) (57.4%) in HCC patients reached 77.0%. HCC patients with multiple tumour foci (7.53 ng/ml; 1.40-29.18 ng/ml) had significantly higher sFas levels than did patients with a solitary tumour (2.70 ng/ml; 0.14-19.0 ng/ml) (P = 0.003). In all of the sFas-positive patients with a solitary tumour, surgical removal of the tumour reduced sFas levels to the negative in the first post-op week. These findings suggest that sFas may be closely linked with HCC and may be a candidate for a clinical parameter for HCC.
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PMID:Elevated serum levels of soluble Fas/APO-1 (CD95) in patients with hepatocellular carcinoma. 964 77

Paraffin-embedded liver tissue from 60 biopsied or autopsied cases, including 20 cases each of acute mild hepatitis, chronic active hepatitis and active cirrhosis were studied with immunohistochemical double labelling technique by using polyclonal anti-Fas and anti-Fas ligand. The detection rates for Fas and Fas ligand were 76.7% (46/60) and 70.0% (42/60), respectively. Fas antigen was located in cytoplasm of hepatocytes. Fas ligand was expressed mainly in infiltrating lymphocytes in portal or periportal areas (34/42, 80.9%) and also in the cytoplasm of some hepatocytes (25/42, 59.5%). The distribution of Fas ligand-positive hepatocytes was similar to that of Fas-positive hepatocytes in liver tissue. The positive cells were scattered in the intralobular areas in acute mild hepatitis, but they were more commonly aggregated in periportal areas, especially near the edges of the piecemeal necrosis region or in infiltrating mononucleocytes in chronic active hepatitis and active cirrhosis, Double labelling studies showed that both Fas and Fas ligand might be expressed in the same or different hepatocytes of the same area. Our results suggest that Fas-Fas ligand system may play an important role in liver cell injury due to hepatitis B virus infection.
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PMID:[Expression of Fas and Fas ligand in liver tissue infected with hepatitis B virus]. 1043 77

The experimental data in recent years suggest apoptosis of liver cells plays a significant role in the pathogenesis of viral hepatitis. Firstly, the number of apoptotic hepatocytes in patients with hepatitis B or C is significantly higher than healthy objects. Secondly, the expression levels of Fas antigen in hepatocytes of patients with hepatitis B or C are closely correlated with inflammation activity. Thirdly, massive apoptosis of hepatocyte will result in fulminant hepatitis, while inhibition of apoptosis can prevent inflammation in experimental model of liver injury. And finally, the occurrence of hepatitis induced by CTL in transgenic mice is a process from hepatocyte apoptosis to liver necroinflammation. This paper will examine our current understanding of the possible relationship between hepatocellular apoptosis and the pathogenetic mechanism of hepatitis B and C.
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PMID:A new hypothesis of pathogenetic mechanism of viral hepatitis B and C. 1135 71

The pathogenesis of the fulminant hepatitis B is poorly understood and both viral factors and the hosts immune response play a role. Previous studies in liver tissues of patients with chronic hepatitis B showed overexpression of Fas antigen and this was correlated with the activity of the hepatitis. The present study was done to determine the role of Fas in fulminant hepatitis B and the virological characteristics of hepatitis B infection. We studied three patients with fulminant hepatitis B. HBV-DNA was detected by dot-blot hybridization and polymerase chain reaction. The S and C gene were sequenced. Levels of serum soluble Fas antigen were detected by enzymoimmunoassays procedure. Apoptosis was determined by the TUNEL technique. Fas antigen expression was evaluated by a immunoperoxidase method. Ten healthy subjects acted as controls. The three patients showed a high expression of Fas antigen particularly among infiltrating lymphocytes; in these areas we also found many cells with in situ DNA nick labelling signals in the nuclei of most viable hepatocytes. Serum levels of soluble Fas antigen were higher in patients with fulminant hepatitis B than in controls. No specific genome mutations of hepatitis B virus were found. These data suggest that the Fas system involved in the liver injury of patients with fulminant hepatitis B.
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PMID:Apoptosis mediated by the Fas system in the fulminant hepatitis by hepatitis B virus. 1187 92

Gene product expression in normal and chronic hepatitis C virus infection was determined in an attempt to improve our understanding of the molecular events leading to the development of cirrhosis and liver carcinoma. Activation of CD95 (Fas) causes apoptosis of cells and liver failure in mice and has been associated with human liver disorders. c-myc is involved in cell proliferation and EGFR in regeneration of cells. The material of the current study included 50 cases of chronic hepatitis C (CHC) (and negative hepatitis B virus infection), 29 cases of liver cirrhosis and HCV (LC), and 19 cases of hepatocellular carcinoma and HCV (HCC) admitted to the Theodor Bilharz Research Institute (TBRI) during the years 2003-2004. Ten wedge liver biopsies - taken during laparoscopic cholecystectomy - were included in the study as normal controls. Laboratory investigations, including liver function tests, serological markers for viral hepatitis and serum alpha fetoprotein level (alpha-FP), were determined for all cases. Histopathological study and immunohistochemistry using monoclonal antibodies for CD95, c-myc and EGFR were also done. In CHC cases, the histological activity index (HAI) revealed more expression of Fas antigen in liver tissues with active inflammation than in those without active inflammation (p < 0.01). EGFR and c-myc act synergistically in liver tumorigenesis. Upregulation of Fas in chronic hepatitis C infection and of c-myc & EGFR in malignant transformation was concluded from this study. c-myc expression may obstruct the induction of apoptosis of HCC cells and lead to uncontrolled cell growth.
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PMID:Immunohistochemical expression of CD95 (Fas), c-myc and epidermal growth factor receptor in hepatitis C virus infection, cirrhotic liver disease and hepatocellular carcinoma. 1685 63

Apoptosis is central for control and elimination of viral infections. In chronic hepatitis C virus (HCV) infection, enhanced hepatocyte apoptosis and upregulation of the death-inducing ligands CD95/Fas occur. This study aimed to study the role of serum soluble Fas and hepatic Fas expression as early predictors of advancement of chronic hepatitis C disease. The current study included 50 cases of chronic hepatitis C (CHC) (and negative hepatitis B virus infection), 30 cases of liver cirrhosis (LC) and HCV, and 20 cases of hepatocellular carcinoma (HCC) and HCV admitted to Theodor Bilharz Research Institute, Giza, Egypt. Fifteen wedge liver biopsies, taken during laparoscopic cholecystectomy, were included in the study as normal controls. Assessment of serum soluble Fas level (sFas) and other laboratory investigations, including liver function tests, serologic markers for viral hepatitis, and serum alpha-fetoprotein level (alpha-FP), were determined for all cases. Histopathologic study and immunohistochemistry using monoclonal antibody for CD95 were also done. The sFas was significantly increased in CHC, LC, and HCC cases compared with normal controls (P < .01). The increase of sFas in HCC was also significantly higher than that of CHC (P < .01). However, positive hepatic expression of Fas antigen was higher in CHC than LC with no significant difference; meanwhile, it was significantly lower in HCC (P < .01) compared with CHC. In conclusion, circulating and hepatic Fas expression in chronic hepatitis C infection illustrate the mechanism of liver injury caused by death receptors throughout the multistep process of fibrosis/carcinogenesis. Not only the higher degree of hepatic fibrosis, but also the lower expression of Fas protein, are correlated with the increased incidence of HCC.
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PMID:Circulating and hepatic Fas expression in HCV-induced chronic liver disease and hepatocellular carcinoma. 1867 33