Immunologic events during the incubation period of hepatitis C virus infection: the role of antibodies to E2 glycoprotein. Multicentre Hemodialysis Cohort Study on Viral Hepatitis.

BACKGROUND: The study of the sensitivity of screening assays is greatly facilitated by testing the sequential changes in seroconverting individuals. The aim of this study was to investigate the early immunologic response after hepatitis C virus (HCV) infection and to evaluate whether HCV envelope (E2) recombinant antigen would provide a significant increase in sensitivity for detection of anti-HCV. STUDY DESIGN AND METHODS: Twenty hemodialysis patients who were seroconverting to anti-HCV were included in this study. They were followed up for a mean period (+/- SD) of 10.5 +/- 3.3 months, in which 13 to 46 serum samples per case were collected. Each sample was tested for anti-HCV by second- and third-generation enzyme immunoassay (EIA-2 and EIA-3) and recombinant immunoblot assay (RIBA-3). E2 antibodies were tested by a prototype EIA in which E2 was expressed as a recombinant antigen in Chinese hamster ovary cells. RESULTS: Alanine aminotransferase elevation was observed in 18 of 20 cases. Reactivity against c100, c33c, c22, NS5, and E2 was detected in 15 (75%), 19 (95%), 15 (75%), 2 (10%), and 17 (85%) patients, respectively; c33c was the most immunogenic antigen, followed in descending order by E2, c22, c100, and NS5. E2 antibody reactivity resolved the two RIBA-3-indeterminate cases. However, there was no case in which E2 reactivity preceded all other HCV antigens. Anti-E2 was found to react in all patients of genotypes 1a, 1b, and 3a but in only 2 of 4 patients of genotype 4a. CONCLUSION: In this group of seroconverting individuals, E2 antigen was shown to be highly immunoreactive and did resolve some RIBA-3-indeterminate samples as being positive, on the basis of reactivity to multiple antigens, but it did not improve early detection of seroconversion.

Hepatitis E virus (HEV) infection in haemodialysis patients. The Multicentre Haemodialysis Cohort Study on Viral Hepatitis.

BACKGROUND: The aim of this study was to determine the prevalence of hepatitis E virus (HEV) infection among patients undergoing haemodialysis (HD) and to evaluate whether chronic haemodialysis is associated with an increased risk of HEV infection. METHODS: Serum samples from 420 HD patients and 316 healthy volunteers were tested for IgG and IgM antibodies to HEV (anti-HEV). Anti-HEV IgG positive sera were confirmed using synthetic peptides. RESULTS: Anti-HEV IgG was confirmed in 27/420 (6.4%) of the HD patients and in 7/316 (2. 2%) of the reference group (P=0.07). However, multiple logistic regression analysis showed that the prevalence of anti-HEV IgG was not significantly higher in HD patients compared with the reference group, after controlling for age and sex. No patient was found positive for anti-HEV IgM. The presence of anti-HEV was associated with sex in HD patients (P=0.04). No significant association was found between anti-HEV and underlying renal disease, anti-HCV, anti-HBc, blood transfusions, history of elevated transaminases, history of clinical hepatitis and renal transplantation. A marginal association, which was observed with the duration of haemodialysis in univariate analysis (P=0.07), was not confirmed in multivariate analysis. CONCLUSIONS: Chronic haemodialysis is not associated with an increased risk of exposure to HEV, and the high prevalence of anti-HEV IgG in HD patients reported in uncontrolled studies is possibly due to the confounding effect of age and sex.