Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Structural and nonstructural regions of the HCV-encoded polyprotein have been expressed in recombinant yeast, bacteria, or insect cells and used to capture and measure reactive antibodies circulating in different individuals. The putative nucleocapsid protein (C) and nonstructural proteins 3-5 (NS3-NS5) were found to contain the most immunodominant epitopes. The NS3, NS4, and C regions were expressed in yeast in the form of a fused, chimeric polyprotein (C25) and a capture assay for reactive antibody was developed. This anti-C25 assay detects all previously identified HCV-seropositive cases and provides a substantially more sensitive diagnostic for both acute and chronic HCV infections than the current anti-C100-3 (NS4) assay. Anti-C25 was detected more frequently than anti-C100-3 in chronic, transfusion-associated non-A, non-B hepatitis patients from the United States (95% vs. 71%) and Japan (98% vs. 82%), in cryptogenic cirrhosis patients from the United States (62% vs. 28%), and in hepatitis B surface antigen-negative cases of hepatocellular carcinoma from Japan (83% vs. 63%). These data indicate that HCV has a greater role in these liver diseases than was previously thought. In volunteer United States blood donors sampled following the introduction of anti-C100-3 screening, the prevalence of anti-C25 and anti-C100-3 was 0.5% and 0.08%, respectively.
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PMID:Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: reevaluation of the role of HCV in liver disease. 127 66

Infection with hepatitis C virus (HCV) was analyzed by an enzyme-linked immunosorbent assay based on recombinant viral proteins encoded by regions of the putative viral core, NS3, NS4 and NS5, which were expressed in E. coli. Results showed that 106 of 124 cases (85.5%) of non-A, non-B chronic hepatitis and 43 of 45 cases (95.5%) of hepatocellular carcinoma, negative for HBV marker, were positive for antibodies against at least one of these viral proteins. One of 87 healthy individuals with normal alanine aminotransferase activity was positive for antibody against only the viral core, but was negative for HCV RNA. The serum of one patient with chronic hepatitis was positive for one of these proteins, but negative for HCV RNA. These findings in combination with results on detection of HCV RNA in the sera of patients with non-A, non-B chronic hepatitis indicated that 105 of 124 cases (84.6%) were positive for HCV infection. Sera that were negative for HCV antibodies against all these proteins were also negative for HCV RNA assayed by reverse transcription followed by the polymerase chain reaction. Screening of HCV infection by detecting viral antibodies in circulating blood using all these viral proteins is useful for reducing the number of ambiguous results in screening for viral infection. Thus, this assay system may be useful diagnostic purposes.
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PMID:Serodiagnostic assay of hepatitis C virus infection using viral proteins expressed in Escherichia coli. 131 40

The hepatitis C virus (HCV) commonly causes persistent infection and chronic liver disease, and it is an important risk factor for the development of hepatocellular carcinoma (HCC). The mechanisms responsible for HCV persistence and disease pathogenesis are not well understood, although it is likely that both direct (virus-induced) and indirect (immunologically mediated) mechanisms play an important role. This review focuses on current knowledge of the interactions between HCV and the host immune system, emphasizing aspects of the cellular immune response. Observations in humans infected with HCV as well as experimental HCV infection of chimpanzees suggest that natural HCV infection does not induce protective immunity at the humoral or cellular levels. Indeed, anti-HCV seroconversion does not prevent reinfection by homologous or independent viral inocula. A CD4+ T lymphocyte response directed against all of the putative viral proteins occurs in chronically infected patients despite their failure to clear the virus. While the HCV core and NS4 proteins seem to be most immunogenic at the CD4+ peripheral blood T cell level during chronic HCV infection, there is some evidence that the NS4-specific response is preferentially compartmentalized in the liver. Similarly, the CD8+ cytotoxic T lymphocyte (CTL) response is remarkably polyclonal and multispecific during chronic HCV infection, since epitopes located in all of the putative proteins are recognized by the CTL present in the peripheral blood and/or the intrahepatic lymphocyte populations during this disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunological aspects of HCV infection. 781 41

Hepatitis C virus (HCV) genotypes (groups I and II) were determined by a newly developed C14 assay in which antibodies against group-specific recombinant proteins of the NS4 region were measured by ELISA (enzyme-linked immunosorbent assay). The genotypes determined by the C14 assay were compared to those determined by a polymerase chain reaction (PCR) in 50 patients. The HCV genotypes determined by both methods were consistent in 78% of the patients. The results of the assays were not contradictory in any patient. The sensitivity of the C14 assay was as high as over 90%. Frequency of HCV genotypes was studied in 300 patients with chronic liver diseases type C by using the C14 assay. The prevalence of groups I and that of II in patients with chronic hepatitis were 73% and 21%, the correspondence figures in those with liver cirrhosis 80% and 13%, and in those with hepatocellular carcinoma 81% and 13%, respectively. The clinical characteristics were similar between the patients with group I and II HCV infections in each disease category. In conclusion, the C14 assay is useful for epidemiological studies of HCV genotypes, and group I is a major HCV genotype of chronic liver diseases type C in Japan.
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PMID:Prevalence of hepatitis C virus with different genotypes determined by a group-specific antibody assay in Japanese patients with chronic liver diseases due to hepatitis C virus infection. 796 59

Infection with the hepatitis C virus (HCV) commonly causes persistent disease, which may lead to cirrhosis and hepatocellular carcinoma. The pathogenesis of HCV infection is not well understood. It is most likely that both viral and host factors contribute to HCV persistence. This review focuses on the host's immune response to HCV in an attempt to present the current knowledge and concepts of the interactions between the virus and the host during HCV infection. Expansion of B lymphocytes and antibody production to virtually any HCV protein can be detected in most infected patients. However, observations in HCV-infected humans as well as experimental infections in chimpanzees suggest that natural HCV infection does not induce protective immunity, and reinfection can readily be demonstrated after inoculation with homologous or independent strains in HCV-seroconverted animals. Nevertheless, the immune system may gain partial control over HCV even in patients with chronic infection, as HCV infection in severely immunocompromised patients runs a particular cholestatic course which may rapidly lead to death from liver failure. Cytotoxic CD8+ T lymphocyte responses to HCV proteins have been characterized in peripheral blood and liver tissue and were found to be remarkably polyclonal and multispecific. Epitopes were identified on all of the putative HCV proteins, although only few major histocompatibility complex molecules were considered restriction elements. Immunoregulation may be particularly important in HCV infection. The HCV core and NS4 proteins appear to be most immunogenic for peripheral blood lymphocytes, and NS4 specific CD4+ lymphocytes are preferentially compartmentalized to the liver. However, there is an inverse relationship between CD4+ lymphocyte responses and antibody levels in infected patients. Furthermore, a strong cellular response to the HCV core protein apparently favors a benign course of infection. This unusual T-B cell relationship may be the consequence of an altered cytokine release during HCV infection. Alternatively, this virus may have found devices that can disturb immunoregulation in infected patients. A better understanding of these immunological mechanisms induced by HCV infection should make it possible to develop more effective strategies for the prevention and treatment of this insidious disease.
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PMID:Immune responses in hepatitis C virus infection. 883 85

A routine screening test used in the diagnosis of hepatitis C virus (HCV) infection is the anti-HCV antibody (anti-HCV) test containing core, NS3, NS4, and NS5 antigens of HCV. When HCV infection occurs in immunocompromised hosts, antibody formation against core, NS3, or NS4 antigens may be weak in the presence of HCV viremia and cannot be detected by routine anti-HCV tests. This study proposed that in immunocompromised hosts such as patients with chronic renal failure (whose capacity to form antibodies is diminished), antibody formation against the E2 region would be preserved, because the E2/NS1 region of HCV is strongly immunogenic. The aim of this study is to evaluate the significance of anti-E2 in the diagnosis of HCV infection among patients on maintenance hemodialysis who are anti-HCV-negative, using a conventional third-generation enzyme immunoassay (EIA) kit. The E2/NS1 gene of HCV encoding the amino acid sequence 388-664 was molecularly cloned into a vector containing an SV 40 promotor and was expressed in Chinese Hamster ovary cells. Using this E2 protein, the anti-E2 test was performed by EIA on 100 patients on maintenance hemodialysis, and on 50 patients with chronic hepatitis C who were anti-HCV-positive, to evaluate the antigenecity of the E2 protein. Of the 100 hemodialysis patients, 15 (15.0%) tested anti-HCV-positive using a third generation anti-HCV ELISA kit. Of the 85 patients who tested negative for anti-HCV, nine (10.6%) were anti-E2-positive and six (66.7%) of these anti-E2 positive patients showed HCV RNA viremia by HCV reverse transcription-polymerase chain reaction. Fourty-two (84.0%) of 50 patients with chronic hepatitis C were anti-E2-positive. As a control group, we tested for anti-E2 among 30 blood donors who were anti-HCV-negative, and also among 85 patients with hepatocellular carcinoma who were anti-HCV-negative, but in both groups, none (0%) was anti-E2-positive. In conclusion, these data suggest that the E2 protein of HCV should be included in a diagnostic anti-HCV kit for the detection of HCV infection in immunocompromised patients.
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PMID:Significance of anti-E2 in the diagnosis of HCV infection in patients on maintenance hemodialysis: anti-E2 is frequently detected among anti-HCV antibody-negative patients. 895 33

Sixteen medical institutions in Japan collaborated in this study of the epidemiology of hepatitis C virus (HCV) genotypes. A total of 4176 patients with type C chronic liver disease, from the four main islands of Japan, were evaluated. Of those evaluated, 2794 had chronic hepatitis, 727 had liver cirrhosis and 655 had hepatocellular carcinoma. The HCV genotype of the patients was determined by an enzyme-linked immunosorbent assay based on serological genotype 1- and 2-specific recombinant peptides (SG-1 and SG-2, respectively) of the NS4 region. The prevalence of SG-1 and SG-2 HCV was similar in the four main islands of Japan. SG-1 HCV predominated in each disease category (69-76%). The percentage of patients with SG-1 HCV increased by 7%, while that of patients with SG-2 HCV decreased by 7%, as liver disease progressed in severity from chronic hepatitis to carcinoma (P < 0.001). Patients with either SG-1 or SG-2 had a similar mean age and history of blood transfusion. In conclusion, SG-1 HCV was found to predominate in Japan, and the HCV genotype was found to be related to the stage of hepatitis C disease.
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PMID:Epidemiology of genotypes of hepatitis C virus in Japanese patients with type C chronic liver diseases: a multi-institution analysis. 896 29

Evidence is emerging that hepatitis C virus genotypes have different carcinogenic potentials. The hepatocarcinogenicity of genotype 5, the predominant subtype in hepatitis C virus isolates in South Africa, is not known. We have compared the prevalence of genotype 5 of hepatitis C virus in 44 southern African blacks with hepatitis C virus-related hepatocellular carcinoma with that in a comparable group of patients with hepatitis C virus-induced chronic liver disease (cirrhosis or chronic hepatitis) in the absence of cancer. Hepatitis C virus serotypes 1 to 6 were identified by measuring type-specific antibodies to NS4-derived peptide antigens. Serotype 5 was present in 48% (21/44) of the patients with hepatocellular carcinoma and 37% (15/41) of those with liver disease in the absence of hepatocellular carcinoma, an insignificant difference. Although the numbers of the other genotypes were small, the differences in the prevalence rates of these serotypes between the two groups of patients were also not significant. We conclude that genotype 5 of the hepatitis C virus is neither more nor less carcinogenic than other genotypes found in isolates in South Africa.
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PMID:Hepatocarcinogenic potential of genotype 5 of hepatitis C virus. 961 95

Exposure to hepatitis C virus (HCV) is associated with a high prevalence of persistent viral infection and the development of chronic liver disease and hepatocellular carcinoma. Recovery from acute infection may depend upon the generation of broad-based cellular immune responses to viral structural and nonstructural proteins. We used the DNA-based immunization approach in BALB/c mice to determine whether the HCV nonstructural proteins NS3, NS4, and NS5 will induce Ab responses, CD4+ Th cell proliferation, and cytokine release in response to stimulation by recombinant proteins as well as generate CD8+ CTL activity both in vitro and in vivo. We found that the nonstructural proteins were particularly good immunogens and produced cellular immune responses when administered as a DNA construct. Indeed, a tumor model was established following inoculation of syngenic SP2/0 cells stably transfected with NS5. We observed protection against tumor formation and growth only in mice immunized with the NS5-encoding DNA construct, establishing the generation of significant CTL activity in vivo by this technique. The results indicate that genetic immunization may define the cellular immune response of the host to HCV nonstructural proteins and is a promising approach for vaccine development.
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PMID:Genetic immunization generates cellular and humoral immune responses against the nonstructural proteins of the hepatitis C virus in a murine model. 979 26

Using 4 McAbs to HCV-C, E, NS3 and NS4 regions' antigens and PcAb to HBsAg, 59 cases of hepatocellular carcinoma(HCC) and 35 cases of liver cirrhosis(LC) were tested by immunohistochemistry technique. Positive reactions for hepatitis C virus were mainly present in the cytoplasm of hepatocytes and tumor cells with fine granules. The positive rates of HCV were 17.2% in HCC(29 cases) of Beijing, 26.7% in HCC(30 cases) of Shenyang and 14.3% in LC(35 cases) of Shenyang. C region's McAb had the highest positive rate of detection, which suggested that C region's protein had a high level expression. The positive rates of hepatitis B virus surface antigen were 63.0% in HCC(29 cases) of Beijing, 73.3% in HCC(30 cases) of Shenyang and 54.3% in LC(35 cases) of Shenyang, all of which were higher than their positive rate for HCV detected. In HCC and LC, HBV and HCV inclined to suppress the opposite side.
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PMID:[Detection of hepatitis C virus-C, E, NS3 and NS4 regions' antigens in hepatocellular carcinoma and liver cirrhosis]. 1252 45


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