Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The agent responsible of more than 80% of the parenterally transmitted non-A-non-B hepatitis, designated hepatitis C virus (HCV), was identified in 1988 thanks to the isolation of the first cDNA reactive clone which was derived from experimentally infected chimpanzees RNA. The recombinant protein expressed from this clone located in the NS4 region of the HCV, allowed to establish the whole HCV-RNA sequence and to develop the first generation enzyme-linked immunoassays for detecting anti-HCV antibodies. Subsequently, other recombinant viral antigens derived from other HCV genome regions, were produced and used to develop second generation screening and confirmatory assays (1991). At least, thanks to a better presentation of the epitopes, since 1993 the performance of third generation reagents have been improved. Nevertheless, in spite of those modifications, the performance of both screening and confirmatory assays still needs to be improved. Moreover, in cases of difficulties of HCV infection diagnosis with serological tests, HCV-RNA detection with genomic amplification tools represents a useful alternative.
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PMID:[Development of a biological diagnosis for hepatitis C]. 926 88

Hepatitis C is the most common cause of post-transfusion hepatitis, as well as of the viral chronic liver disease in the western world. However since it is even more often asymptomatic than HBV, this is not truly recognized. The detection of hepatitis C can only rely on serological and virological methods and require their extensive use in screening programs. Following the molecular identification characterisation of HCV, it became possible to detect virus specific antibodies. The first generation Elisas were limited in their scope and have been replaced by second and third generation tests with better sensitivity and specificity. These assays detect antibodies to several sets of HCV protein including the C22 core, the C33 and C100, which correspond to the non structural regions (NS3 and NS4 respectively). More recently, NS5 proteins have also been added and synthetic peptides have replaced some of the recombinant proteins used initially. In spite of improved sensitivity and specificity, last generation Elisas still require confirmation by supplemental assays which can be of different types (immunoblot or combined Elisas) and include sets of structural and non structural recombinant proteins or peptides. New tests are needed to improve sensitivity and proficiency of this mandatory confirmation procedure. It is unclear at this stage whether the dogma inherited from HIV to request two sets of reactive antibodies will be also warranted by experience in HCV infection. The biggest limitation of present HCV tests is the delayed appearance of anti-HCV following primary infection. Even more worrisome is the fact that 10% of chronic infection with liver disease still remain seronegative, despite circulating HCV RNA in serum and/or liver as well as expressing HCV antigen demonstrable in liver tissue by immunostaining. Such a proportion is even more common in settings with immune deficiencies including organ transplantation and HIV infection. DNA amplification methods, such as PCR or others, must be used in order to demonstrate HCV RNA in combination with reverse transcription steps. This new powerful technology must be however applied under stringent quality control procedures and cannot be yet considered for screening or routine diagnosis although it can detect viremia as early as a week after exposure and help to monitor interferon treatment. During acute hepatitis, the delay in the appearance of anti-HCV hampers acute phase diagnosis. The early detection of HCV RNA in peripheral blood, confirms the diagnosis and opens up therapeutic possibilities. In chronic hepatitis, the diagnosis of seronegative forms may only be resolved by PCR. Moreover, the presence of HCV RNA in peripheral blood represents the only marker of on going viral replication and coincides with the severity of liver damage. During treatment with interferon, the follow up of HCV RNA sequences makes it possible to monitor its efficacy. The search for HCV RNA sequences directly in liver tissue shows that HCV may replicate in the liver in the absence of viremia. The presence of HCV RNA in the liver and the serum of liver transplanted patients is essential for the etiological diagnosis and management of hepatitis and bone marrow failure occurring after transplantation. Epidemiological study using PCR is a major tool in documenting vertical transmission between mother and child. Finally, PCR is important for the analysis of the HCV genome. Thus, in France there are at least three main strains, one close to the US prototype, the other close to the Japanese strain, possibly responsible for a more severe illness, and a third one distinct from the previous two. Two major HCV genotypes, F1 and F2, corresponding to HCV type I and II (USA prototype and Japanese) with prevalence of 45% and 55% respectively, were found in France. F1 infected patients were younger and more often male than F2 group. Nine of 28 patients in F1 genotype infected group had history of drug abuse but none i
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PMID:[Limits of immunoserologic and molecular diagnosis of hepatitis C]. 929 65

NS4, a nonstructural protein of HCV, is a frequent target of antibodies in infected subjects. According to recent data, the antibodies frequently recognize the sequence 1921-40 of the NS4 protein. The aim of this work was to analyze antibody reactivity with the sequence 1921-40 in different HCV-related disorders. Although this sequence is located in a relatively invariant region of viral genome, two strain-specific sequences are described. Thus, three NS4 1921-1940 peptides were synthesized: the BK shared by most viral strains, the J6 (strain 2a), and the J8 (strain 2b). The peptides were used as antigens in the solid phase for measuring serum IgG antibodies in an ELISA assay. Antibodies reactive with the 1921-40 BK peptide were detected in 64% of sera from patients with autoimmune hepatitis (AIH), 51% from chronic hepatitis C (CHC), and 22% from mixed cryoglobulinemia (MC). The frequency of positive sera in MC was significatively lower than in AIH (P < 0.0001) or CHC (P < 0.0021). Similar results were obtained with the J6 and J8 peptides. All sera that did not react with the BK peptide were negative on J6 and J8 and conversely most sera reacting with the BK peptide also bound the J6 and the J8 peptides. No correlation was found between the genotype of the infecting virus and the presence of antibodies to any of the NS4 peptides. These results indicate that many HCV-infected subjects produce antibodies to the NS4 sequence 1921-40. The immune response to this sequence is not strain specific and varies with the different disorders associated with HCV infection.
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PMID:Immune response to an epitope of the NS4 protein of hepatitis C virus in HCV-related disorders. 961 26

To investigate the role of hepatitis C virus (HCV) quasispecies mutation in the pathogenesis of HCV infection, we analyzed changes in the genetic diversity of HCV genomes in 22 patients before and after liver transplantation by using heteroduplex mobility assay (HMA) technology. All patients were infected with HCV genotype 1 and developed high-titer posttransplant viremia. Each patient was classified according to the severity of posttransplant hepatitis, as assessed by standard biochemical and histological criteria. HCV quasispecies were characterized by HMA analysis of eight separate subgenomic regions of HCV, which collectively comprise 44% of the entire genome. The glycoprotein genes E1 and E2, as well as the nonstructural protein genes NS2 and NS3, had the greatest genetic divergence after liver transplantation (the change in the heteroduplex mobility ratio [HMR] ranged from 2.5 to 7.0%). In contrast, genes encoding the core, NS4, and NS5b proteins had the least amount of genetic divergence after liver transplantation (range, 0.3 to 1.2%). The E1/E2 region showed the greatest change in genetic diversity after liver transplantation, and the change in HMRs was 2.5- to 3.3-fold greater in patients with asymptomatic or moderate disease than in those with severe disease. The E1-5' region of HCV quasispecies isolated from patients in the asymptomatic group had a significantly greater degree of diversification after liver transplantation than the same regions of HCV quasispecies isolated from patients in the severe disease group (P = 0.05). While changes in the genetic diversity of some nonstructural genes were also greater in asymptomatic patients or in patients with mild disease than in patients with severe disease, the results were not significant. Data from this cohort demonstrate that greater rates of HCV quasispecies diversification are associated with mild or moderate liver disease activity in this immunosuppressed population.
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PMID:Multigene tracking of hepatitis C virus quasispecies after liver transplantation: correlation of genetic diversification in the envelope region with asymptomatic or mild disease patterns. 981 42

Hepatitis C virus (HCV), the major causative agent of post transfusion non-A, non-B hepatitis (NANB), had been cloned and expressed. According to the protein sequence of HCV-BK and its epitope profiles which combined the hydrophilicity, accessibility, flexibility, antigenicity, charge distribution and HPLC reserve coefficient of protein using the "Goldkey" computer program, we designed and synthesized the following peptides: P1(475-495), P3(449-468), P4(658-663), P5(645-663), P6(484-489), P7(475-489), P15(655-662), P16(230-237), P17(225-237), P18(1220-1240), P19(1694-1735), P24(1230-1240), P25(1482-1493), P26(384-389), P27(2355-2389). The results of ELISA showed that P6(60% positive results) and P19(63% positive results) testing with PT-HC of Gu An, Hebei province were the major antigens in NS1 and in NS4 region, respectively.
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PMID:[Studies on synthetic peptide. XX: the antigenicity and linear epitope map of synthetic peptide hepatitis C virus]. 986 43

To examine the prevalence of hepatitis G virus (HGV) and hepatitis C virus (HCV) infections in deceased injection drug users and for comparison of the detection rates of HGV and HCV RNA in liver tissue with detection rates in postmortem serum samples, RT-PCR was performed in 50 drug abuse-related fatalities. HGV RNA was detectable in liver tissue samples from 17/50 suddenly deceased drug abusers (34%). In 16 of these 17 positive cases, serum samples were also available but HGV RNA was detected in only 10. From 29/50 anti-HCV positive individuals, HCV RNA was detected in 23/50 liver tissue samples (46%), but HCV RNA was detectable in only 6/22 of the corresponding serum samples. In 12 anti-HCV positive cases (10 being also positive for HCV RNA in the liver), the examinations revealed a coinfection with HGV by detection of HGV RNA in the liver tissue samples. A significant association between the detection of HCV RNA in the liver and the occurrence of antibodies against the HCV NS4 protein, but not against HCV core antigen or NS3 protein was observed. The probability of anti-HCV and HCV RNA positivity increased with the age of the individuals. No HGV or HCV infection was detected in a control group of 50 persons who died suddenly by violent impact. The prevalence of active HCV and HGV infections in injection drug users detected by RT-PCR in liver tissue is in good accordance with data obtained from sera from living injection drug users. In contrast, the detection rate in postmortem serum samples was clearly lower. Possible reasons for this observation are discussed and the use of liver tissue for postmortem detection of hepatitis virus RNA is recommended.
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PMID:Higher detection rate of hepatitis G and C virus RNA in liver tissue than in serum of deceased injection drug users. 993 40

The HLA class II-restricted T-cell response to hepatitis C virus (HCV) antigens is believed to influence the final outcome of hepatitis C, because it is vigorous in patients who recover from acute hepatitis C, but it is weak in those who develop a chronic infection. For this reason, exogenous stimulation of T-cell responses in chronic HCV infection may represent a strategy to cure patients with chronic hepatitis C by approximating the vigor of their T-cell reactivity to that of patients who succeed in recovering from hepatitis. It may also be a preventive approach to avoid spread of the virus by facilitating the development of a vigorous protective response at the very early stages of infection. T-cell-based vaccines composed of immunodominant, promiscuous, and conserved T-cell epitopes may represent a powerful tool to achieve optimal stimulation of the T-cell reactivity. To identify HLA class II-restricted T-cell epitopes useful for this purpose, 22 subjects with acute HCV infection were studied and followed for an average time of 29 months. Eight of them recovered from hepatitis, and 14 developed a chronic infection. Overlapping 20-mer peptides covering the entire core and NS4 antigens and a panel of peptides representing highly conserved regions of core, NS3, NS4, and NS5 were used. By direct peripheral blood T-cell stimulation and by fine-specificity analysis of HCV-specific T-cell lines and clones, highly immunogenic T-cell epitopes were identified within core, NS3, and NS4. All these epitopes are immunodominant and highly conserved among the known HCV isolates. Moreover, they are promiscuous, because they can be presented to T cells by different HLA class II molecules. Immunodominance, sequence conservation, and promiscuity make these epitopes ideal components of preventive or therapeutic T-cell-based vaccines against HCV.
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PMID:Conserved hepatitis C virus sequences are highly immunogenic for CD4(+) T cells: implications for vaccine development. 1049 64

Since January 6th 1994 to december 31 1997. We researched hepatitis C Virus antibodies by second and third generation ELISA in 34,130 bloods donors living in "Sahel Tunisien". 193 were positive (0.56%). Only 171 of them were secondary tested by immunoblot assay (anticore, anti NS5, anti NS3, anti NS4). Which was positive in 53 cases (30.9%); in determined (presence of only one antibody) in 78 cases (45.6%) and negative, in 40 cases (23.3%). There was a significant relation between a ratio over than 2.5 in ELISA and immunoblot positivity. Immune response to different hepatitis virus antigens were heterogeneous with predominant in determined profile. (78/171 cases). Most of donors of the last profile had either anti NS5 (32/78) or anti NS3 (33/78) and we excluded them even through usually negative in P.C.R and associated with a very low risk of contamination.
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PMID:[Hepatitis C virus antibodies in 34130 blood donors in Tunisian Sahel]. 1089 44

A double polymerase chain reaction, involoving nested primers deduced from NS3-5 regions of the hepatitis G virus (GBV-c/HGV) genome, was developed for a sensitive and specific detection of GBV-C (HGV) RNA. With this method, 10 anti-HGV positive patients with non A-E hepatitis and 10 healthy subjects were tested. Among 10 patients, GBV-C RNA was detected in 9, 8, 4, 9 patients by the NS-3 (1) primers, the NS3(2) primers, the NS4 primers, the NS5(1) primers and the NS5(2) primers respectively. Control sera from 10 healthy subjects did not reveal GBV-C (HGV) RNA by any set of the primers. These data suggest that the detection rate of GBV-C (HGV) RNA is different in various set of primers, the NS3(1) and the NS5(2) primers are superior to other primers and are more suitable for RT-PCR of GBV-C (HGV) RNA.
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PMID:[Detection of hepatitis G virus RNA in sera in non A-E hepatitis patients using polymerase chain reaction with multiple set primers]. 1561 20

The authors studied the levels of cytokines (interleukin (IL)-1, IL-2, IL-4, IL-6, and interferon-gamma (IFN-gamma)) and cell response to HBV and HCV in the dynamics in patients with acute mixed hepatitis (B+C) who recovered or became chronically ill, as well as before and after treatment of hepatitis C. Patients who later recovered had high levels of IL-2 and IFN-gamma during the acute phase of the disease, and displayed T-lymphocyte sensitization to HbeAg, Hbcore Ag, and the non-structural protein HCV NS3. A significant elevation of IL-2 level and, especially, IFN-gamma level, as well as the appearance of T-lymphocyte response to HCV NS3, HCVcore Ag, and HCV NS4 was observed during antiviral therapy.
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PMID:[Clinical significance of cytokine level and T-cell lymphocyte response to B and C hepatic viral antigens in patients with type C and B+C hepatitis receiving antiviral therapy]. 1788 15


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