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)

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

In 1974, Prince et al. reported the existence of posttransfusion hepatitis with a long incubation period which was not related to hepatitis B virus (HBV). These cases were named "non-A, non-B" (NANB) hepatitis. The genome of NANB hepatitis virus was discovered recently using a recombinant complementary DNA (cDNA) approach. It was termed the hepatitis C virus (HCV), and a specific diagnostic tool for the circulating HCV antibody (anti-HCV) was developed using a purified viral polypeptide derived from recombinant yeast expressing a small part of the HCV genome. HCV is believed to be the main cause of blood-borne non-A, non-B hepatitis worldwide, which frequently evolves to chronic hepatitis and cirrhosis, and which may also be involved in the development of hepatocellular carcinoma. HCV is classified as part of the flaviviridae family and contains a positive-stranded RNA molecule by approximately 10 kb nucleotides. The HCV genome encodes a large polyprotein precursor, which is processed in structural nucleocapsid and envelope proteins and in non-structural proteins (NS1-NS5). Nucleotide sequence comparisons of distinct HCV isolates have shown a significant genetic variability between the different HCV strains. At present the diagnosis of HCV infection depends on various anti-HCV tests including second generation HCV Ab. Antigenic markers for HCV are being developed but the concentrations of HCV antigens in serum are at the lower limit of detectability by existing immunoassay technology. A polymerase chain reaction has been used to detect HCV RNA in the serum and liver. Serum HCV RNA disappears from serum after effective IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fundamental studies of hepatitis C virus: a review]. 133 74

Hepatitis C virus is a positive single-strand RNA virus distantly related to flaviviruses. Therefore RNA replicase, an RNA-dependent RNA polymerase, may be essential for the replication of hepatitis C virus, as well as other RNA viruses. In this study we synthesized the recombinant polypeptide (HCV-NS5 antigen) with a 576 bp cDNA encoding a part of the NS5 region of the HCV genome that has the Gly-Asp-Asp motif. The antibody against this polypeptide was obtained from rabbit serum. In Western-blot analysis with NS5 IgG HCV antibody, an 84-kD protein was clearly detected as a single band in the microsomal fraction but not in the nuclear and mitochondrial fractions or in the cytosol fraction. Immunohistochemically, HCV-NS5 antigen was clearly stained in the cytoplasm of hepatocytes but not in the nucleus or cell membrane. Moreover, as determined on immunoelectron microscopy, HCV-NS5 antigen was demonstrated with fine granular distribution along the endoplasmic reticulum but not in other organelles, including the nucleus and mitochondria. Immunoreaction in other cell types was negative. These results indicate that replication of HCV may occur only in hepatocytes and that HCV-NS5 may be produced in the endoplasmic reticulum of these cells. HCV-NS5 antigen was stained only in the livers of hepatitis C virus-positive patients but not in sections from patients with chronic type B hepatitis or alcoholic fibrosis. In chronic type C liver disease, the overall detection rate of HCV-NS5 antigen was 56% (33% in chronic persistent hepatitis, 52% in chronic active hepatitis and 86% in cirrhosis).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of antigens related to hepatitis C virus RNA encoding the NS5 region in the livers of patients with chronic type C hepatitis. 750 61

The authors investigated the epidemiology of hepatitis C virus (HCV) related to liver diseases in Korea. Anti-HCV was studied by EIA in sera from patients with chronic liver diseases (CLD), individuals at high risk, healthy individuals, and family members of patients with CLD. We also evaluated the efficacy of a new anti-HCV assay kit, HCD EIA, consisting of 3 recombinant peptides derived from CORE, NS3 and NS5 regions of the HCV genome, for screening HCV infection. The prevalence of anti-HCV in HCD EIA was 15.4% of 1055 cases studied, while that in the anti-C100-3 EIA was 11.1%. The incidence of anti-HCV in HCD EIA was 5.9% of 17 cases with acute hepatitis, 18.1% of 293 cases with chronic hepatitis, 24.1% of 79 cases with liver cirrhosis, 28.0% of 100 cases with hepatocellular carcinoma, 19.8% of 81 cases maintained with hemodialysis, 31.3% of 16 cases with blood dyscrasias, 4.4% of 114 cases with fatty liver, 1% of 100 healthy persons, 1.3% of 150 blood donors, and 6.2% of 97 family members from 26 patients with type C CLD. Familial HCV clustering was detected in 3 (11.5%) of 26 patients with anti-HCV(+) CLD. The prevalence of anti-HCV in 190 HBsAg positive CLD was 8.4%. The relative proportions of positive anti-HCV, HBsAg, both positive 17.4%, 40.7%, and 3.7%, respectively, while 38.2% of the cases were negative for both anti-HCV and HBsAg. The prevalence of anti-HCV among CLD increased significantly in relation to age (p < 0.05), and it became higher than that of HBsAg after age 60.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of hepatitis C virus related to liver diseases in Korea. 768 3

We tested HGV RNA in serum in addition to HBV DNA and HCV RNA to study the causative agents involved in chronic non-B, non-C hepatitis. Twenty five patients diagnosed as having chronic non-B, non-C hepatitis(negative for HBsAg and HCV-Ab), were investigated in this study. HGV RNA was detected by nested RT-PCR using primers in 5'-untranslated, NS3 and NS5 regions. Of the 25 patients, 4(16%) were positive for HGV RNA, only 1(4%) was positive for HBV DNA and none were positive for HCV RNA. Of the 4 patients with HGV RNA, 2 histologically has mild fibrosis and the remaining 2 had cirrhosis. One patient with cirrhosis also had hepatocellular carcinoma; HBV DNA was positive in this patient. All 3 patients with only the HGV infection had a mild histological grade. In conclusion, HGV infection was involved in 16% of Japanese patients with chronic non-B, non-C hepatitis. Chronic hepatitis G seemed to exhibit mild hepatitis activity.
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PMID:[GB virus C/hepatitis G virus infection in patients with chronic non-B, non-C hepatitis]. 908 58

Hepatitis C virus (HCV) represents one of the major causes of acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) around the world. Our knowledge of the life cycle of HCV, however, is limited. Current studies are hampered by the lack of a reproducible, high-level in vitro replication system of HCV. We sought to establish HCV replication in HepG2 cells by gene transfer of in vitro transcribed HCV RNA. In preliminary experiments, diethylaminoethyl-dextran led to more efficient gene transfer than cationic liposomes (lipofectin, lipofectamine, and DOTAP). Therefore, in subsequent experiments, HepG2 cells were transfected with full-length (9.6-kb) and near-full-length (9.4-kb) HCV RNA using diethylaminoethyl-dextran. Transfection with subgenomic HCV RNA and mock transfection were used as controls. Positive- and negative-strand HCV RNA sequences were detected by reverse transcription polymerase chain reaction (KT-PCR) for 60 days in the infectious HCV RNA transfected HepG2 cells. The presence of negative-strand HCV RNA, presumably representing replicative intermediates, was confirmed by ribonuclease protection assay. The intracellular levels of HCV RNA were measured by quantitative competitive RT-PCR from 10 to 50 days after transfection and were stable over this time period at moderately high levels (10(8) to 10(10) genomes per mg of total RNA). Expression of viral core and nonstructural proteins was detected in the cytoplasm of transfected cells by immunostaining. Virus-like particles measuring 50 to 60 nm in diameter were found by electron microscopy in cytoplasmic vesicles and conditioned media of the cells transfected with infectious HCV RNA but not in cells transfected with truncated HCV RNA. Culture supernatants of infectious HCV RNA transfected HepG2 cells were infectious for Daudi cells for three passages tested. The truncated HCV RNA lacking NS5 and 3' untranslated region (3' UTR) of HCV was replication incompetent. This is the first demonstration of HCV particles in HepG2 cells after transfection with infectious HCV RNA. We conclude that we have established a reproducible HCV replication system in HepG2 cells that can be used to study the life cycle of HCV and to test anti-HCV agents.
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PMID:Transfection of HepG2 cells with infectious hepatitis C virus genome. 925 Jan 50

Virus-specific CD4(+) T-cell response at the site of inflammation is believed to play a decisive role for the course of viral disease. In hepatitis C virus (HCV) infection, the majority of studies focused on the peripheral blood T-cell response. In this study we analyzed intrahepatic virus-specific CD4(+) T-cell response and compared this with that in the peripheral blood. Liver and blood-derived T-cell lines were studied in 36 patients (18 with chronic hepatitis C and 18 with HCV-associated cirrhosis). Virus-specific interferon gamma (IFN-gamma) production at a single cell level to various HCV-proteins (core, nonstructural [NS] 3/4, NS5) were determined by enzyme-linked immunospot (ELIspot). Phenotyping was done by fluorescent-activated cell sorter analysis. In approximately half (16 of 36 [44%]) of intrahepatic T-cell lines a significant number of IFN-gamma spots were observed, whereas this was the case in only 19% (7 of 36 T-cell lines) in the blood. In relative terms, core and nonstructural proteins were recognized with the same frequency in both compartments, but HCV-specificity was significantly more often detected in liver tissue compared with the blood. Hepatitis activity index, viral load, and alanine transaminase levels did not correlate with the detection of HCV-specific CD4(+) T cells. All T-cell lines were dominated by CD4(+) T cells. In conclusion, HCV-specific CD4(+) T cells are multispecific, compartmentalize to the liver, and produce IFN-gamma. We speculate that our data would support the concept of compartmentalization of specific T cells at the site of inflammation and that a low frequency of specific T cells is associated with failure to clear the virus and a chronic course of disease.
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PMID:Liver-derived hepatitis C virus (HCV)-specific CD4(+) T cells recognize multiple HCV epitopes and produce interferon gamma. 1096 Apr 55

OBJECTIVE: To undertake a comparative evaluation of diagnostic modalities used in the detection of hepatitis C virus (HCV) infection by serum antibody in ELISA and HCV-RNA in the serum as well as in the liver tissue of the same patients with chronic liver disease by reverse transcription-polymerase chain reaction (RT-PCR). METHODS: Thirty-five subjects comprising 30 cases of cirrhosis of the liver and five cases of chronic hepatitis were included in the study group. The criteria for including the subjects in the study were the availability and quality of serum and liver samples. Serologic ELISA tests for HCV antibody as well as HBsAg and anti-HBc IgG for hepatitis B virus (HBV) were performed on the patient's sera, while RT-PCR was carried out with RNA extracted from both serum and liver biopsies of the patients. Primer sequences selected from the conserved NS5 region of the HCV genome were used in RT-PCR. RESULTS: Of 30 cases of cirrhosis studied, five (16.6%) were anti-HCV antibody positive, while seven (23.3%) were positive for HCV RNA in serum and 10 (33.3%) were positive in liver tissue. One of the anti-HCV antibody-positive patients was negative for HCV RNA in both liver and serum by PCR. All seven patients who showed positivity for HCV RNA in serum were also positive for HCV RNA in the liver. Another three cirrhosis cases (10%) found to be HCV positive in liver tissue were negative for both antibody and HCV RNA in serum. Of the five cases of chronic hepatitis, two (40%) were found to be positive by all three tests. HCV was found to be more prevalent in HBV-infected cases (8/18; 44.5%). However, two of the three cirrhotic patients who showed HCV positivity only in liver PCR tested negative for HBV surface antigen. CONCLUSIONS: RT-PCR detection of HCV RNA in liver tissue is of significant clinical importance and is more reliable than RT-PCR in serum or antibody tests by ELISA. RT-PCR can effectively complement antibody tests for reliable diagnosis, since assessment of HCV positivity by a single test seems to be inadequate. The frequent association of HCV infection with HBV suggests that hepatitis B and C viruses may share similar modes of transmission in India.
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PMID:Comparative evaluation of hepatitis C virus infection in serum and liver tissue of patients with chronic liver disease by reverse transcription-polymerase chain reaction. 1185 64

The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy.
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PMID:Course and outcome of hepatitis C. 1240 73

Persons with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection are at increased risk for progression to cirrhosis compared with persons with HCV alone, but the reasons for this are unclear. In chronic HCV, the mechanism of liver injury is presumed to be due to HCV-specific T cell destruction of hepatocytes, so it is paradoxical that immunosuppressed hosts have higher rates of fibrosis progression. We examined intrahepatic cellular immune responses to HCV antigens to determine whether there were qualitative or quantitative differences in subjects with and without HIV. Expanded, CD4-enriched, liver-infiltrating lymphocytes from 18 subjects with chronic HCV and 12 subjects with HIV/HCV were cultured in the presence of HCV core protein, nonstructural proteins NS3 and NS5, and recall antigens tetanus toxoid and Candida. Secretion of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin (IL) 10 was determined using enzyme-linked immunosorbent spot assay. There were no significant differences in liver biopsy grade or stage for HIV/HCV versus HCV groups. There were no significant differences between groups in the secretion of IFN-gamma or TNF-alpha in response to HCV or recall antigens. However, there was a significant increase in IL-10 secretion in response to NS3 and NS5 in subjects with HCV compared with HIV and HCV coinfection. In conclusion, subjects with coinfection have an alteration of intrahepatic HCV-specific IL-10 cytokine response that may have implications for HCV-related disease progression.
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PMID:Comparison of HCV-specific intrahepatic CD4+ T cells in HIV/HCV versus HCV. 1523 95


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