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)

Hepatitis G virus (HGV) is a recently discovered RNA virus, which belongs to the Flaviviridae family. Although HGV infection is usually not associated with elevated serum transaminases, some recent studies have reported that HGV infection is found in a significant number of patients with fulminant hepatitis and may play a role in its etiopathogenesis. In this study the prevalence of HGV infection was determined in 500 healthy blood donors and in 24 patients admitted to hospital because of acute liver failure caused by fulminant hepatitis. The presence of HGV RNA was tested in sera, obtained at admission and before any transfusion was given, by a sensitive seminested reverse transcriptase-polymerase chain reaction (RT-PCR) assay specific for detection of the non-structural (NS)5 region. Nine of the 500 blood donors (1.8%) and two of the 24 patients (8.3%) were found to be HGV RNA positive. One patient was co-infected with HCV and was known to be an intravenous (i.v.) drug user. After intensive supporting treatment, this patient recovered completely. The second patient had no serological markers of known viral hepatitis infection, including hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV). This patient was successfully transplanted. From both patients, from HGV RNA-positive healthy blood donors and from other patients coinfected with HCV, a part of the HGV NS3 region (nucleotides 4191-4345, EMBL entry U45966) was cloned and sequenced. Sequence comparison revealed that the NS3 region of HGV in patients with fulminant hepatitis contained three nucleotide substitutions as part of the six substitutions described in previous work. These nucleotide substitutions were not found in the tested blood donors or in patients with HCV co-infection. Our findings therefore support the concept of the association of fulminant hepatitis with infection of a specific HGV strain.
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PMID:Hepatitis G virus infection in acute fulminant hepatitis: prevalence of HGV infection and sequence analysis of a specific viral strain. 979 13

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

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 prevalence of GB virus C (GBV-C) in candidate Brazilian blood donors with normal and elevated alanine aminotransferase levels was found to be 5.2% (5 of 95) and 6.5% (5 of 76), respectively. Among Brazilian patients, GBV-C was found in 9.5% (13 of 137) of cases of hepatitis not caused by hepatitis A virus (HAV), HBV, HCV, HDV, or HEV (non-A-E hepatitis) and in 18.2% (8 of 44) of individuals infected with HCV. Molecular characterization of GBV-C by partial sequencing of the NS3 region showed clustering between members of a single family, implying intrafamilial transmission. In conclusion, these results together suggest that contagion mechanisms which facilitate intrafamilial transmission of GBV-C may partially explain the high prevalence of viremic carriers worldwide.
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PMID:High prevalence of GB virus C in Brazil and molecular evidence for intrafamilial transmission. 1020 45

Serological research suggests that hepatitis B virus (HBV) and hepatitis C virus (HCV) are associated with the development of hepatocellular carcinoma (HCC). It is unclear how genes of hepatitis viruses participate in hepatocarcinogenesis in patients infected with HCV. We investigated the expression of hepatitis virus-related RNAs in resected liver from 51 patients with HCV antibodies (Ab) and without hepatitis B surface antigen (HBsAg). mRNA transcripts of the genes HBx, HBc, HBs, nonstructural (NS) region 3 of HCV, the 5'-untranslated region (UTR) of HCV, and the 5'-UTR of hepatitis G virus (HGV) were amplified by reverse-transcription polymerase chain reaction (RT-PCR) with specific primers for each gene. The HBx transcript was detected in 19 (37%) tumors and in 8 (16%) specimens of noncancerous tissues (P =.014). The NS3 gene of HCV was detected in 35 (69%) tumors and 41 (80%) noncancerous tissues. HGV RNA was detected in 3 tumors (6%). Patients with HBx transcripts were younger than patients without HBx transcripts (P =.012). HBx transcripts were detected in 3 (33%) of 9 well-differentiated HCCs, in 8 (31%) of 26 moderately differentiated HCCs, and in 8 (50%) of 16 poorly differentiated HCCs. Codon 130 (AAG) and codon 131 (GTC) of HBx were changed to ATG and ATC, respectively, in all HCCs with HBx transcripts. In conclusion, we found that the HBx gene was expressed in many HCCs; the gene might promote hepatocarcinogenesis in patients with HCVAb and without HBsAg, but HGV is not closely related to hepatocarcinogenesis in such patients.
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PMID:Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in Japanese patients with hepatitis C virus. 1021 26

The concept of chronic hepatitis induced by alcohol (AL-CH) has not been widely accepted, because AL-CH may be due to non-A-E hepatitis virus in heavy drinkers. Recently, hepatitis G virus (HGV) was identified as a positive-strand RNA virus related to members of the Flaviviridae family. In this study, we determined serum HGV in patients with AL-CH and analyzed the clinicopathological changes after abstinence to evaluate whether AL-CH is caused by alcohol or not. Serum samples were obtained from 16 patients with AL-CH who had neither hepatitis B nor C virus. The diagnosis was confirmed histologically. In eight patients, liver biopsy was performed twice, within 3 days and 4 to 8 weeks after abstinence. The NS3 region of the HGV genome was detected using an reverse transcriptase-polymerase chain reaction method. Serum levels of AST, ALT and gamma-glutamyltranspeptidase were measured once a week sequentially after admission. Serum HGV-RNA was detected in only one patient with AL-CH (6.3%). In all patients, including one patient with HGV, serum levels of AST, ALT and gamma-glutamyltranspeptidase clearly decreased to normal levels after abstinence. Inflammatory activity in the periportal area of patients with actively drinking decreased or disappeared after abstinence for 4 to 8 weeks. These results suggest that HGV may not play an important role for development of AL-CH, and that AL-CH may be caused by alcohol itself, although a more larger number of patients with AL-CH are needed to obtain definitive conclusions.
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PMID:Clinicopathological study of chronic hepatitis induced by alcohol with or without hepatitis G virus. 1023 75

The nucleotide sequence of hepatitis GB virus type C (HGBV-C)/hepatitis G virus (HGV) NS3/helicase and 5'-untranslated regions from 23 Spanish patients were analyzed to assign the HGV isolates one of the proposed HGBV-C/HGV genotypes. The analysis of the evolutionary distance frequency showed that the distances among all sequences in NS3/helicase region were distributed around a single peak of 0.20, suggesting that all included sequences belonged to the same HGBV-C/HGV genotype. By contrast, in the 5'-untranslated region, all the distances corresponding to our sequences and those of the HGBV-C/HGV types 2 and 3 were distributed around a major peak of 0.03. The remaining distances corresponding to the HGBV-C/HGV type 1 sequences were distributed around a minor peak of 0.11. The phylogenetic tree and pairwise comparison of evolutionary distances among the 5'-untranslated region of the infected patients and each HGBV-C/HGV genotype demonstrated that our HGBV-C/HGV isolates belonged to subtype 2a (17/23; 78%) and 2b (5/23; 22%). No relation was found between HGBV-C/HGV subtype and hepatitis B or C virus infection.
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PMID:Phylogenetic analysis of hepatitis GB virus type C/hepatitis G virus in Spanish patients with chronic hepatitis B or C virus infection. 1032 32

To study non-parental transmission of hepatitis G virus and/or GB virus C (HGV/GBV-C), we sequenced and compared the NS3/helicase region of the virus for five HGV/GBV-C RNA-positive mothers and their 11 children who had experienced neither blood transfusion nor overt hepatitis and were negative for HBV, HCV and HIV, except in one mother coinfected with HCV. The nucleotide sequences of the familial HGV/GBV-C isolates showed high similarity of 99-100% (mean 99.8%, 100% at the deduced amino acid level) between mother and her child(ren) in each family. These findings strongly suggest the spontaneous occurrence of mother-to-child transmission of HGV/GBV-C as reported previously. They also suggest that nucleotide sequence analysis on the NS3/helicase region of HGV/GBV-C may be a useful tool to study HGV/GBV-C transmission.
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PMID:Partial nucleotide sequencing of the NS3/helicase region of hepatitis G virus to prove vertical transmission. 1038 79

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


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