Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fas antigen (ag) is a cell surface protein known to trigger apoptosis in a variety of cells upon specific antibody binding. On the other hand, Bcl-2 protein, an oncogene product located at the mitochondrial inner surface, prolongs cell survival by blocking apoptosis. In this study we examined the expression of Fas ag and bcl-2 protein in 17 cases of hepatocellular carcinoma (HCC) to determine their role on HCC. By flow cytometric analysis, mean (SD) value of the expression of Fas ag on hepatocytes derived from normal liver, diseased liver (chronic hepatitis or liver cirrhosis) and HCC was 5.8 (4.7)%, 10.3 (6.9)%, and 24.0 (18.2)%, respectively. Fas ag expression on hepatoma cells was significantly greater than normal and diseased liver cells. The expression of Bcl-2 protein in normal liver, diseased liver and HCC was 4.3 (8.5)%, 0.8 (2.5)% and 2.1 (3.4)%, respectively, and the difference was not significant. These results suggest that induction of apoptosis may be a possible therapy against HCC.
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PMID:Expression of Fas antigen and Bcl-2 protein in hepatocellular carcinoma. 750 84

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

The primary diseases of 209 explanted livers of the transplantation center of the University of Heidelberg are presented. Liver cirrhosis was found in 48.8% as the primary disease followed by the group of malignancies of the liver (28.2%) with HCC as the predominant tumor. Fulminant liver failure was found in 13.8% as the primary disease. Metabolic disorders comprised a small group of 11 cases (5.3%). 7 cases were transplanted for Budd Chiari syndrome (3.3%) and one case was transplanted for E. alveolaris. The examination of fulminant viral hepatitis revealed evidence of the involvement of the APO-1/Fas (CD95) system in the pathogenesis of this disorder. Prognostic factors for recurrence of hepatocellular carcinoma are size and number of tumor nodules as well as proliferative activity of the tumors determined by Ki67 immunostaining. Diagnosis of HCV infection of the livers is best established by RT-PCR after RNA extraction and is still superior to other immunohistochemical or in-situ methods.
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PMID:[Pathology of the explanted liver in liver transplantation]. 860 Jun 90

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

To date, there have been no reports of the involvement of the Fas system in recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT). In 25 patients who underwent OLT for HCV-related liver cirrhosis, we evaluated the expression of the Fas antigen (FasAg) on hepatocytes, apoptic hepatocytes, and serum levels of soluble Fas (sFas). The level of HCV viremia and HCV genotype were determined by polymerase chain reaction. Serum sFas levels were determined by an enzyme immunoassay procedure. DNA fragmentation was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) technique on deparaffinized liver samples. FasAg expression was evaluated by an immunoperoxidase method. Sixteen patients had evidence of recurrent HCV disease. The number of hepatocytes expressing FasAg and the percentage of apoptotic hepatocytes was greater among patients who developed recurrent hepatitis than among those who did not (P <.01 and P <.0001, respectively). There was a correlation between hepatic expression of FasAg, intensity of lobular inflammation (P =.007), and TUNEL index (P <.001). The levels of sFas were greater among the patients with recurrent HCV hepatitis than those without recurrent hepatitis (P <.04). We conclude that (1) Fas expression is up-regulated in recurrent HCV after OLT and is related to the grading of liver disease; likewise, levels of sFas were greater in the patients with recurrent HCV hepatitis; and (2) the demonstration of hepatocytes with FasAg expression and the labeling of the nuclei by TUNEL assay suggest that hepatic apoptosis mediated by the Fas system may have a role in the pathogenesis of recurrent HCV hepatitis after OLT.
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PMID:Involvement of the fas system in hepatitis C virus recurrence after liver transplantation. 1098 54

We aimed to determine serum soluble Fas antigen (sFas) levels at various stages of hepatitis C virus (HCV)-induced liver disease, and investigate correlations between serum sFas levels and clinical, biochemical and pathologic features. Sixty-five patients were categorized into five groups: 1, chronic active hepatitis C, elevated alanine aminotransferase (ALT), HCV-polymerase chain reaction (PCR) positive; 2, responders to interferon + ribavirin therapy; 3, cirrhosis; 4, chronic hepatitis C, normal ALT, HVC-PCR positive; and 5, sustained responders. Group 6 comprised 15 control individuals. Serum sFas levels were measured by enzyme-linked immunosorbent assay. Significant differences in serum sFas levels were found between the following groups: 1 and 2; 1 and 3; 1 and 4; 1 and 6; and 3 and 6. Serum sFas levels did not correlate with ALT, histological activity or HCV-PCR positivity within group 1. Serum sFas levels appear to increase in advanced stages of HCV-induced liver disease, as a result of host-related immunological factors.
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PMID:Elevated serum soluble Fas levels in the various stages of hepatitis C virus-induced liver disease. 1458 5

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

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.
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PMID: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. 2369 29


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