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)

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

Hepatitis C virus (HCV) is a recently described causative agent of the great majority of post-transfusion non A-non B hepatitis and is classified within the Flaviviridae family. Due to a high prevalence of anti-HCV and other flaviviruses circulating in Brazil, such as dengue and yellow fever, we investigated the possibility of serological cross-reactivity between these viruses. Different panels of human sera positive for dengue type 1 (9 cases) and type 2 (7 cases) from 6 patients naturally infected with yellow fever and from 94 adults vaccinated against the 17D strain of yellow fever were tested against HCV antigens used in diagnostic assays. Two enzyme immunoassay systems were tested: one, an in-house test using recombinant antigens from core, NS3 and NS5 regions of the HCV genome (Research Foundation for Microbial Disease of Osaka University, Japan); and another, using synthetic peptides representing immunodominant epitopes of structural core and non-structural NS4 and NS5 HCV regions (INNOTEST HCV Ab, Innogenetics, Belgium). A line immunoassay (INNO-LIA HCV Ab, Innogenetics, Belgium) was used as a confirmatory test. In this, HCV antigens are coated as discrete lines on a nylon strip with plastic backing. Besides 4 control lines on each strip, a total of 6 HCV lines are present: line A consists of several NS4 epitopes, line B consists of several NS5 epitopes and lines C-F contain several core epitopes. This test not only confirms but differentiates antibodies to hepatitis C virus. No positive results were detected with these tests, indicating that hepatitis C infection can be evaluated by current assays in regions where flaviviruses are endemic.
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PMID:Human antibodies to dengue and yellow fever do not react in diagnostic assays for hepatitis C virus. 128 68

Serial serum samples from cardiac patients with a history of chronic or resolved post-transfusion non-A, non-B hepatitis were analyzed by a combination of cDNA synthesis and the polymerase chain reaction (cDNA/PCR) to amplify HCV RNA. Analysis of sera drawn after the acute hepatitis episode from 8 of the patients who had an acute, resolving HCV infection showed no detectable levels of HCV RNA when primers from the NS3 region were used. Evaluation of these sera with primers from the 5'-untranslated (5'-UT) region revealed that one patient was positive for HCV RNA. Further analysis of serial serum samples available from two of these patients indicated that a resolved infection was associated with a disappearance of detectable HCV RNA after a peak level during the acute phase of the disease. In contrast, post-acute samples from 4 of 6 patients with symptomatic acute HCV infection evolving to chronicity were positive for HCV RNA using primers from the NS3 region, however, upon retesting with primers from the 5'-UT region, all 6 patients were found to be positive. Analysis of serial serum samples from 2 of these patients showed the persistence of HCV RNA in 70% of the samples. These two patients were subsequently treated with interferon alpha-2b. One patient resolved his disease and normalized his aminotransferase level during treatment and thereafter, while the other relapsed upon cessation of treatment. In these two patients, normalization of ALT levels was consistent with the absence of HCV RNA while relapse of disease was confirmed by the reappearance of detectable levels of HCV RNA. These results indicate the utility of HCV RNA as a marker for persisting HCV viremia and in differentiating patients with ongoing active HCV infection from those with an acute resolving disease.
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PMID:Detection of hepatitis C viral RNA by the polymerase chain reaction in serum of patients with post-transfusion non-A, non-B hepatitis. 131 77

We obtained a cDNA clone representing a partial RNA sequence of a human hepatitis C virus (HCV) isolate from Southern California. RNA was extracted from the liver tissue of a patient with post-transfusion hepatitis, and used for cDNA synthesis and polymerase chain reaction (PCR) amplification using oligonucleotide primers specific for the prototype HCV RNA. The cDNA clone obtained contains 585 base pairs of HCV sequences and represents the region encoding the putative nonstructural protein NS3 of HCV. Sequence analysis of this clone showed that it shares 93.8%, 78.7% and 79.6% similarity, respectively, with the previously published American, Japanese and Taiwanese isolates at the nucleotide level, indicating the heterogeneity of HCV RNA in different geographic areas. By contrast, it shares 97.3%, 92.9% and 92.9% with these respective isolates at the amino acid level, suggesting the functional conservation of viral genes.
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PMID:Molecular cloning and sequence analysis of an isolate of hepatitis C virus from Southern California, U.S.A. 136 14

28 patients with posttransfusion non-A, non-B (NANB) hepatitis in Stockholm, Sweden, were studied for seroconversion to hepatitis C virus antibodies (anti-HCV) and time lag to seroconversion by first and second generation tests. 15/28 patients (54%) seroconverted to anti-HCV with a first generation anti-HCV ELISA using C100-3 from the nonstructural (NS) region 4 of the HCV genome and 23 (82%) with a second generation anti-HCV ELISA including also antigens from the core and NS3 regions of the HCV genome. The mean time from onset of hepatitis to seroconversion was 6.1 weeks (0-18 weeks) with the first generation test and 2.3 weeks (0-7 weeks) with the second generation test. Development of chronic hepatitis was noticed in 14/23 (61%) patients who seroconverted to anti-HCV with the second generation ELISA and in none of 5 patients with posttransfusion NANB hepatitis who did not seroconvert. The inclusion of antigens from the core and NS3 regions of the HCV genome has increased the sensitivity of the second generation anti-HCV ELISA as compared to the first generation ELISA and also shortened the time lag to seroconversion in patients with posttransfusion hepatitis C. Patients with posttransfusion NANB hepatitis seroconverting seem more prone to develop chronic disease than patients not seroconverting.
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PMID:Seroconversion to hepatitis C virus antibodies in patients with acute posttransfusion non-A, non-B hepatitis in Sweden with a second generation test. 137 90

A screening assay for the detection of antibodies to hepatitis C virus (HCV); ORTHO HCV ELISA Test System, Second Generation, was compared with the currently licensed c100-3 based test (ORTHO HCV ELISA Test System). The second generation ELISA differs from the c100-3 based assay in that it detects circulating antibodies to both structural (nucleocapsid) and non-structural (NS3/NS4) HCV proteins. Specimens tested consisted of a cohort of 35 patients diagnosed with non-A, non-B hepatitis (NANBH) and 3971 presumably healthy volunteer blood donors. Second generation ELISA demonstrated significantly greater clinical sensitivity in patients with acute phase NANBH (80% vs. 60%) as well as chronic disease (88% vs. 72%). Additional specimens reactive only in second generation ELISA, demonstrated reactivity to HCV antigens c33c and/or c22-3 in supplemental testing by the Chiron HCV RIBA Assay System. The second generation ELISA also detected additional RIBA reactive volunteer blood donors (0.18% of the population tested) that were nonreactive in first generation ELISA. This data indicated that second generation ELISA would detect approximately 2 additional anti-HCV reactive donors per 1,000 screened. Specificities obtained with this low risk population were 99.6% for first generation and 99.7% for second generation ELISA.
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PMID:Improved detection of antibodies to hepatitis C virus using a second generation ELISA. 138 Nov 39

Although sensitive assays for serum antibodies to hepatitis C virus (HCV/anti-HCV) have been developed recently, the relation of anti-HCV to HCV infection of the liver has not been clarified. Therefore, we determined the presence of HCV RNA by the reverse transcription-polymerase chain reaction (PCR) in liver biopsy specimens of 21 patients with chronic liver disease and 5 control patients. RNA was extracted from frozen liver tissues by the guanidinium method, HCV cDNA was synthesized by reverse transcription, and core region and NS3 region sequences were amplified by PCR. The sensitivity and specificity of the reaction was significantly enhanced by double PCR with nested primers followed by Southern blotting with an HCV specific oligomer probe. NS3 region sequences were detected in the liver specimens of 12 out of 15 anti-HCV positive patients. Core region sequences were detected in 9 patients, all of whom were also positive for NS3 region sequences. HCV sequences were not detected in 11 anti-HCV negative patients. In all cases, the integrity of the extracted RNA was demonstrated by successful amplification of albumin mRNA as internal control. Our findings demonstrate the feasibility of the reverse transcription-double PCR method followed by Southern blotting for the detection of HCV sequences in liver tissues. In this system, the detection rate of NS3 region sequences is higher than that of core region sequences. There is a statistically significant correlation between high titer anti-HCV antibodies in serum and NS3 region sequences in liver tissue. However, not all anti-HCV positive patients had HCV positive hepatitis. The reverse transcription-polymerase chain reaction for HCV sequences on liver tissue extracts may reveal valuable information on the diagnosis of HCV infection and the pathogenesis of chronic hepatitis C.
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PMID:Detection of hepatitis C virus sequences in liver tissue by the polymerase chain reaction. 165 40

The polymerase chain reaction (PCR) detected specific hepatitis C viral (HCV) RNA sequences in liver biopsies from two patients with chronic hepatitis, in the tissue of a liver implantate, in plasma from four chronic non-A, non-B hepatitis (NANBH) patients and, for the first time, in an infectious anti-D-immunoglobulin preparation. A comparison of the viral sequences coding for a region for the nonstructural NS3 protein from the liver tissues revealed only a very small degree of sequence divergence on the cDNA as well as on the amino acid level (between 0 and 5%). The sequence similarities of the RNA isolated from plasma of the four chronic NANBH patients and the anti-D-immunoglobulin preparation were partly somewhat lower but altogether also high (between 90 and 100%). In contrast, all eight cDNA and amino acid sequences exhibited a significantly higher degree of divergence in comparison with the HCV prototype sequence (between 29 and 32%) than among themselves (between 0 and 10%). This unexpected high sequence similarity of the eight European isolates and their low homology to the Northamerican prototype sequence is indicative for the existence of different types of HCV. This will be important not only for epidemiological studies but also for the development of effective diagnostic procedures and vaccines. Concerning the pathogenesis of NANBH, a double infection or a helper mechanism has to be considered: in addition to the C virus, sequences of an other virus particle were found in the infectious IgG preparation as well as in the liver biopsies.
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PMID:[Hepatitis C virus: sequence homology of a European isolate and divergence from the prototype]. 165 62

cDNA clone 11-7 was isolated by immunoscreening a cDNA library that was prepared from a pooled plasma of non-A non-B hepatitis (NANBH) patients using expression vector lambda gt11. This cDNA corresponds to known nucleotide positions 3983-4745 of the genome of hepatitis C virus (HCV). This clone was used as a probe for screening the HCV-related cDNAs in a cDNA library similarly prepared by using lambda gt10. As a result, six more cDNA clones were isolated and analyzed for their nucleotide sequences. The results strongly suggested that there are at least two groups of HCV, group I and group II. According to our classification, the prototype HCV and clone 11-7 belong to group I HCV, and their nucleotide and deduced amino acid sequences were diverged from those of group II HCV. Genetic variation observed in the nucleotide and the amino acid sequences between the two groups resembles that in the NS3 region of the genome between Japanese encephalitis virus and West Nile fever virus. Polypeptides produced in Escherichia coli carrying a clone 11-7 or a group II cDNA clone E reacted with antibodies in the blood of 12 or 4 out of 14 individual chronic NANBH patients, respectively. Our data clearly indicate the existence of a second group of HCV.
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PMID:A second group of hepatitis C viruses. 166 93

The nucleic acid sequence of the putative 5'-untranslated (5PUT) region of hepatitis C virus (HCV), determined for samples obtained from a variety of geographic origins, was found to be over 98% conserved among all isolates. On the basis of this signature sequence for HCV, a viral RNA assay was developed by using cDNA synthesis with reverse transcriptase, followed by polymerase chain reaction (PCR). The new assay was compared with the Ortho-Chiron C100-3 HCV enzyme-linked immunosorbent assay to research radioimmunoassays for antibodies to the C33c and C22 HCV antigens and to the first reported set of HCV PCR primers designed from the NS3 domain. Plasma samples from 16 Japanese patients with non-A, non-B hepatitis (NANBH) and 16 immunoassay-positive blood donors from the United States were investigated. The 5PUT PCR primers were found to be superior to the NS3 primers in sensitivity and specificity (15 of 25 versus 3 of 25 of the C100 enzyme-linked immunosorbent assay-positive samples, respectively). Samples from two C100-negative patients with acute NANBH were found to react with the 5PUT primers but not with the NS3 primers. Also, two of three patients with chronic NANBH converted from reverse transcriptase PCR positive to negative after interferon treatment. Although the clinical significance of the presence or absence of HCV RNA in samples from patients is not fully understood, the use of probes and primers from the 5PUT region (as opposed to primers from other segments) should not lead to false-negative results due to nucleic acid sequence variations in viral isolates.
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PMID:Use of a signature nucleotide sequence of hepatitis C virus for detection of viral RNA in human serum and plasma. 166 10


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