摘要:

SUMMARY.Chronic infection with the hepatitis C virus is a major health problem. Conventional therapy, with interferon‐α is effective in only a minority of patients. The failure of current treatments has led to a major initiative to identify new antiviral agents. In the absence of a tissue culture model for hepatitis C infection the phwaceutical industry has been obliged to investigate the basic biology of hepatitis C viral replication. Such studies have identified novel translational regulatory elements and new proteolytic enzymes which may serve as targets for new antiviral dru

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00066.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY.Recombinant hepatitis C virus (HCV) core protein from aal‐164, designated cpl‐10, was used to immunize mice. Antibodies to cpl‐10 were produced in all seven strains of congenic mice; none of the strains could be considered low responders relative to the others. The mouse response against individual epitopes of HCV core protein varied from one strain to another: B1O.RIII (H‐2r) recognized all three peptides aa13–30, aa77–90, aa129–145; B10.D2 (H‐2d), B10 (H‐2b) and C3M.SW (H‐2b) responded to aa13–30, aa77–90; B10, M (H‐2f), B1O.BR (H‐2k) and C3H/HeJ (H‐2k) reacted with aa13–30 only. Competitive inhibition of binding demonstrated that antibody to the peptide was inhibited by cpl‐10 protein and the corresponding peptide only. Recombinant HCV core protein is highly immunogenic and can elicit good antibody response in mice. The aa13–30 is a major epitope of HCV core protein in mice. The humoral response to the distinct epitopes was regulated by the H‐2 genes. Further analysis indicated that the I‐a locus of H‐2 genes determined the antibody response to aa13–30 and 77–90. These results suggest that the variation of antibody responses to HCV in humans may partially cont

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00067.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY.Hepatitis B virus (HBV) variants containing mutations within the X and the precore regions of the viral genome were demonstrated by polymerase chain reaction (PCR) amplification and DNA sequencing in renal dialysis patients with different serological patterns of HBV infection. Among carriers, X region deletion mutants predominated in patients who lost hepatitis B e antigen (HBeAg), or developed anti‐HBe, but not in persistently HBeAg‐positive patients. The precore region remained wild type in all carriers whether or not they seroconverted from HBeAg to anti‐HBe. The frequency of precore and X region mutants was greatest among non‐carrier patients with viral antibodies as the only indication of infection and among patients with non‐A, non‐B hepatitis (NANBH), suggesting an inverse relationship between the presence of wild type HBV markers and the presence of HBV mutants. Furthermore, the detection of one but not the other mutation in many serum samples suggests that these mutations are independently selected for during infection. Finally, the absence of HBV DNA in 21 ‘uninfected’ dialysis patients with normal transaminases and no viral serology, suggests that replication of these mutants is associated with hepatitis. These results have important implications for HBV screening and treatment, as well as for the pathogenesis of ch

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00068.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY.Different genotypes of hepatitis C virus (HCV) have been shown to have distinct geographical distribution and to associate with variable clinical features. To evaluate their role in chronic hepatitis in Italian patients, we studied 495 consecutive cases with chronic hepatitis C seen in nine sentinel centres homo geneously distributed over Italy. HCV genotyping was carried out using a dot‐blot hybridization assay with genotype‐specific probes. Four hundred and eleven patients were viraemic and could be evaluated: 57% were found to be infected with HCV‐1,31% with HCV‐2, 8% with HCV‐3. 1% showed mixed infection and 3% were ascribed to HCV‐2b or HCV‐4 by direct sequencing. Geographical distribution showed discrete territorial variations. A history of drug addiction was commoner in patients infected with HCV‐3. There were no signifi cant differences in activity of liver disease among different HCV genotypes but the response to interferon therapy was reduced in patients infected with HCV‐1 compared

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00069.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY.Chronic coinfection with the hepatitis B (HBV) and hepatitis δ (HDV) viruses is known to cause severe liver disease, but the importance of coinfection with hepatitis C virus (HCV) and HBV has not been well documented. In the present study, the clinical and pathological severity of liver disease among patients with hepatitis resulting from multiple viruses was examined and an open trial of the efficacy of interferon‐α2b (IFN‐α) treatment was conducted. Nineteen patients with chronic HBV and HCV infection and 17 with HBV, HCV and HDV infection were studied: 12 in each group underwent liver biopsy. For each coinfected patient, two patients infected with HCV alone were selected as controls, and these were matched for age and risk factor and were estimated to have been infected for a similar duration. Coinfection with HBV and HCV or HBV, HCV and HDV was associated with more severe liver disease than HCV alone (P<0.01); total Scheer score, portal and lobular inflammation and fibrosis were all worse in coinfected subjects. Eight patients with chronic HBV and HCV were treated with recombinant IFN‐α2b [3 million units (MU), thrice weekly for 6 months]. Liver function tests normalized in two patients and one lost hepatitis B surface antigen (HBsAg). Seven patients with hepatitis B, C and δ coinfection were treated with the same regimen and only one normalized serum alanine aminotransferase (ALT) during (and after) treatment. It is concluded that coinfection with multiple hepatitis viruses is associated with histologically more severe liver disease than HCV alone. Short‐and long‐term responses to doses of IFN‐α that are used to treat HCV are infrequent, but further studies are required to determine whether higher‐dose IFN‐α may benefit patients with combined hepa

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00070.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY.Blood donor screening for hepatitis C virus (HCV) antibodies is now routine. Most blood transfusion services recommend that seropositive donors are referred for further investigation. Southern European studies suggest that many asymptomatic seropositive donors have clinically significant liver disease. Seropositive donors in areas of high prevalence may not, however, be representative of British donors. We have prospectively examined the prevalence and severity of HCV infection in a British volunteer blood donor population. During a 14 month period, only 0.35% (999/287 332) of all donors in the West Midlands were anti‐HCV (screening assay) positive. Only 5% (521999) of these were confirmed true seropositive. Nearly 80% (41/52) of seropositive donors were referred to the Queen Elizabeth Hospital Liver Unit for further investigation. Most underwent complete investigation, including liver biopsy. Forty of forty‐one donors had biochemical, histological, or virological evidence of persistent viral infection. Histological changes were generally mild and none was cirrhotic. Covertly infected patients had less severe disease than those with an overt risk factor for HCV exposure. In the British Midlands, the prevalence of blood donor seropositivity is low. In contrast with seropositive Southern European donors, the British donor is more likely to belong to an at‐risk group for parenteral exposure and is less likely to have severe histological changes. This study highlights the importance of developing locally relevant guidelines for the counselling and investigation of anti‐HCV‐positive blo

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00071.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SUMMARY.We have compared two different second‐generation (2.O) enzyme‐linked immunosorbent assays (ELISA) for the presence of antibodies to hepatitis C virus (anti‐HCV) in blood from volunteer, unpaid donors. At two separate blood centres, a total of 21431 donor samples were tested with Abbott Anti‐HCV 2.0 ELISA and Ortho Anti‐HCV 2.0 ELISA. Samples found to be repeatedly reactive were tested by supple‐mental/investigational assays, MATRIX HCV (Abbott) and anti‐HCV RIBA II (Ortho/Chiron), to ‘confirm’ the presence of anti‐HCV. Discordant ELISA samples were additionally tested by the polymerase chain reaction (PCR) for the presence of HCV RNA. The Abbott anti‐HCV assay had a repeatedly reactive rate of 0.59% (127/21431) and the Ortho anti‐HCV assay 0.51% (110/21431). Overall agreement between assays was 99.76%. 72/127 (56.7%) of Abbott repeatedly reactive samples confirmed on MATRIX and 61/127 (48.0%) on RIBAII; 70/110 (63.6%) of Ortho repeatedly reactivate samples confirmed on MATRIX and 61/110 (55.5%) on RIBA II. Discordant ELISA samples tested by PCR yielded negative results. Hence the two ELISA had equal sensitivity, as defined by detection of true positive samples: the slightly lower specificity of the Abbott Anti‐HCV 2.0 ELISA may be owing to culling of donors with a false positive test by Ortho's Anti‐HCV 1.0 and 2.0 ELISA tests (the routine tests in place at each blood centre). A sample found to be repeatedly reactive by two different ELISA tests for anti‐HCV is likely to be a true positive and may not require f

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00072.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00073.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY