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)

While hepatitis C virus (HCV) is a major etiological agent of post-transfusion and community acquired non-A, non-B hepatitis, little is known about the epidemiology of HCV in the UK. A cost-effective method using dried blood spots to determine anti-HCV IgG in subjects which could be used in large-scale epidemiological studies is described. Samples were screened using an in-house IgG ELISA incorporating the recombinant proteins c22-3, c200, and NS5, while specific antibody to HCV was confirmed using a modified immunoblot RIBA 3.0. A panel of well evaluated anti-HCV positive and negative samples from the UK and South Africa were used to assess the sensitivity and specificity of the 2 tests. All anti-HCV positive samples were detected by the in-house screening EIA. Test/negative optical density ratios showed that more than 95% of reactive samples produced values greater than 5.0. Antibodies to HCV could be detected in a wide range of samples derived from asymptomatic and symptomatic patients and of different genotypes, with similar sensitivity. The presence of anti-HCV could be confirmed by RIBA 3.0 in samples with low reactivity, but not in anti-HCV negative samples. The immunoblot assay increased specificity by screening out false reactive EIA samples.
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PMID:A method for the detection and confirmation of antibodies to hepatitis C virus in dried blood spots. 938 10

Assays that detect antibody to hepatitis C virus (HCV) are used to screen blood donors and patients with hepatitis. Current enzyme-linked immunosorbent assay (ELISA)-based methods are invariably based upon antigens from expressed recombinant proteins or oligopeptides from HCV type 1. Some HCV antigens used in screening assays are coded by regions of the HCV genome that show extensive variability; therefore, HCV type 1-based assays may be less effective for the detection of antibody elicited by infection with other genotypes. In this study, we have measured antibody reactivity of sera from 110 hepatitis C patients infected with type 1b, 3a, or 4a to genotype-specific and cross-reactive epitopes present in recombinant proteins from HCV genotypes 1b (core, NS3, and NS5), 3a (NS3, NS5), and 4a (core, NS3), corresponding to those used in current third-generation screening ELISAs. By comparing the serological reactivities of sera to type-homologous and type-heterologous antigens, we detected a significant type-specific component to the reactivity to NS3 (61 to 77% of the total reactivity) and NS5 (60% of the total reactivity). Furthermore, despite the similarities in the amino acid sequences of the core antigens of type 1b and type 4a, we also found significantly greater reactivity to type-homologous antigens, with approximately 25% of reactivity being type specific. These findings are consistent with previous findings of fivefold weaker reactivity of sera from HCV type 2- and HCV type 3-infected blood donors in the currently used third-generation ELISAs and suggest that these assays are suboptimal for screening populations in which the predominant genotype is not type 1.
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PMID:Antigenic variation of core, NS3, and NS5 proteins among genotypes of hepatitis C virus. 939 95

Recently, a new virus related to flaviviruses, the hepatitis G virus (HGV), or GBV-C virus, was discovered as a putative blood-borne human pathogen. HGV RNA (NS5 region) was amplified by reverse transcription-nested PCR in the sera of 6 of 64 (9%) hemodialysis patients; 2 of 80 (2.5%) West Yukpa Amerindians, a population with a high rate of HBV infection but negative for HCV infection; and 1 patient with an acute episode of non-A, non-B, non-C hepatitis (NABCH). The patterns of single-strand conformation polymorphism of the amplified products were unique among different specimens and similar on follow-up for hemodialysis patients. All patients tested remained HGV RNA positive 1 and 2 years later, without major sequence variation, except for the NABCH patient, for whom a double infection and an apparent clearance of the original dominant variant was observed after 2 years. The sequences of the NS5 amplified products demonstrated 85 to 90% identity with other reported HGV sequences.
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PMID:Hepatitis G virus infection in Amerindians and other Venezuelan high-risk groups. 946 61

A novel virus (GBV-C/HGV) may be associated with some liver diseases including fulminant hepatitis and acute and chronic hepatitis. On the other hand, many investigations showed that this infection does not contribute to liver disease. GBV-C/HGV has been found to occur in association with infection with other hepatitis viruses. We investigated the effect of GBV-C/HGV infection on the clinical features and interferon treatment in patients with chronic hepatitis C. A total of 262 hepatitis C virus (HCV) RNA positive patients with chronic hepatitis were examined in this study. The detection of serum GBV-C/HGV RNA was done by RT-PCR using specific primers from the NS5 regions. Interferon-alpha was given at a dose of 6 MU/day for 16 or 24 weeks. A responder was defined as a patient with ALT normalization and HCV RNA disappearance after treatment. GBV-C/HGV RNA was detected in 28 (11%) patients. No significant difference was detected in clinical features (age, sex, liver-related biochemical tests, and histological examination) between the 28 GBV-C/HGV-positive patients and the GBV-C/HGV-negative patients. Using interferon therapy for hepatitis C, the responder rates of GBV-C/HGV-positive and -negative patients were 14% and 20%, respectively. Of the 28 patients with GBV-C/HGV RNA, GBV-C/HGV RNA was tested after interferon therapy in 16 and of these GBV-C/HGV RNA was not detected in nine patients after therapy. These findings suggest that GBV-C/HGV infection dose not affect the clinical features in patients with HCV and the efficacy of interferon therapy for chronic hepatitis C.
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PMID:GBV-C/HGV infection in chronic hepatitis C patients: its effect on clinical features and interferon therapy. 959 28

Excluding acute hepatic failure caused by drugs, the etiology of fulminant hepatitis (FH) remains unknown in many patients. There are conflicting data about a possible pathogenic role for the hepatitis G virus (HGV) in patients with cryptogenic fulminant hepatitis (non-A-E FH). We investigated the presence of circulating HGV in 36 patients with well-documented non-A-E fulminant and 5 patients with subfulminant hepatitis from 3 geographic locations in the United States. Serum HGV RNA was determined by reverse transcriptase-polymerase chain reaction using primers from the NS5 region of the HGV genome. HGV RNA was also measured before and after liver transplantation in 5 patients and at different time points in 7 patients. Serum samples were recoded and reanalyzed for HGV RNA using different primer sets to assess the validity of the HGV RNA assay. HGV was present in serum of 14 of the 36 patients (38.8%) with non-A-E fulminant hepatitis. Twenty percent of patients from the Northeast, 11% of the patients from the Southeast, and 50% from the Mid-Atlantic regions of the United States had circulating HGV RNA. The use of therapeutic blood products was significantly associated with the presence of serum HGV RNA (P <.02). Retesting for HGV RNA with different primers was positive in all but 1 case. HGV RNA is not causally related to non-A-E fulminant hepatitis. The finding of HGV RNA in serum from these patients is likely related to the administration of blood product transfusion after the onset of fulminant hepatitis.
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PMID:The significance of hepatitis G virus in serum of patients with sporadic fulminant and subfulminant hepatitis of unknown etiology. 1043 34

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

Individuals infected with hepatitis C virus (HCV) usually produce anti-HCV antibodies detectable by enzyme immunoassay (EIA); however, in certain viremic cases this antibody does not appear. To investigate whether anti-HCV in these cases is detectable by Western blot (WB), 38 HCV RNA positive/anti-HCV EIA-negative sera were tested by RIBA 3.0 or LiaTek III. The HCV genotypes (INNO-LiPA) were analyzed to determine whether the variance in these genotypes can be the reason for the late, weak antibody production or its absence. As the control group, 282 EIA-positive/HCV RNA-positive patients were examined. A single band reactivity of various intensities by RIBA or LiaTek was observed in 16/38 EIA negative sera. Positive results with NS3 were detected in 4 sera and weak positive (+/-) with core, NS3, and NS5 in 5, 6, and 1 sera, respectively. In 3 cases with anti-NS3, the seroreversion was observed in follow-up. The distribution of genotypes in anti-HCV-negative versus anti-HCV-positive groups was: 1b alone, 50.0% vs. 78.0%; 3a alone, 13.2% vs. 15.6%; and mixed (1b+3a), 36.8% vs. 5.0%, respectively. The follow-up studies showed that viremia was lost spontaneously in 12/35 patients. In some patients infected with two genotypes, the spontaneous loss of the 3a genotype was observed. The study showed that WB tests are useful for serological confirmation of HCV infection in some EIA negative/HCV RNA-positive patients but, because seroreversion may occur, sequential sera samples should be tested. No unusual HCV genotype was detected in anti-HCV-negative/HCV RNA-positive cases, but the frequency of mixed infection with the 1b+3a genotypes in this group was found to be higher than that in anti-HCV-positive hepatitis patients.
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PMID:Anti-HCV RIBA/LiaTek reactivity and HCV genotype in EIA-negative patients with viremia. 1053 25

Seven healthy macaques were inoculated with the GBV-C/HGV-RNA serum from a non-A-E hepatitis patient. The serology and pathology of the liver in the animals were observed. The results indicated that all inoculated animals were infected with a GBV-C/HGV-RNA viremia and had mildly abnormal alanine transaminase levels during the infectious period. The histology, immuno-histochemistry, and in situ hybridization in the liver tissues of the inoculated animals also showed that there was a very mild hepatitis with the positive antigenic expression and the genome of GBV-C/HGV-NS5 in hepatocytes. The pathological changes in the infected animals appeared to become normal whether or not GBV-C/HGV-RNA viremia persisted. There is a possibility that the mild virulence of the GBV-C/HGV to the host became harmless with time after inoculation. Infection and the transmission of the GBV-C/HGV virus in the macaques provides an appropriate animal model and new information about GBV-C/HGV infection in both humans and animals. It is possible that this virus is a mild and self-limited pathogenic agent to the hepatic cells of primates.
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PMID:Serological and histological findings in infection and transmission of GBV-C/HGV to macaques. 1056 59

Efficient transfer of proteins or nucleic acids across cellular membranes is a major problem in cell biology. Recently the existence of a fusogenic sequence was predicted in the junction area of the PreS2- and S-domain of the hepatitis-B virus surface antigens. We have identified cell permeability as a novel property of the PreS2-domain. Cell permeability of PreS2 is not restricted to hepatocytes. PreS2 translocates in an energy-independent manner into cells and is evenly distributed over the cytosol. Detailed analysis revealed that cell-permeability is mediated by an amphipatic alpha-helix between amino acids 41 and 52 of PreS2. Destruction of this translocation motif (PreS2-TLM) abolishes cell permeability. PreS2-TLM per se can act as a shuttle for peptides and functional proteins (such as EGFP). This permits the highly specific modulation of intracellular signal transduction by transfer of peptides competing protein-protein interactions as demonstrated by specific inhibition of TNFalpha-dependent activation of c-Raf-1 kinase. Moreover in vivo functionality was demonstrated by PreS2-TLM-dependent protein transfer into primary bone marrow cells and into the liver. The amphipatic motif is conserved between the different hepatitis-B virus subtypes, and the surface proteins of avian and rodent hepadnaviruses exhibit similar amphipatic peptide sequences. In respect to hepatitis-B virus-infection, the PreS2-TLM could represent the postulated fusion peptide and play a crucial role in the internalization of the viral particle.
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PMID:Novel cell permeable motif derived from the PreS2-domain of hepatitis-B virus surface antigens. 1082 1

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


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