Influence of viraemia and genotype upon serological reactivity in screening assays for antibody to hepatitis C virus

Abstract

Detection of antibody to recombinant proteins derived from hepatitis C virus (HCV) genotype 1 represents the principal method for diagnosis of HCV infection. A method was developed for quantifying antibody reactivity in two third-generation enzyme immunoassays (Ortho EIA 3.0 and Murex VK48), and the influence of viraemia, HCV genotype, and host factors such as age, gender, and risk group upon antibody levels were investigated in a consecutive series of 117 anti-HCV-positive volunteer blood donors. Viraemic donors (as assessed by the polymerase chain reaction; PCR) showed significantly higher levels of anti-HCV by the Ortho EIA than those who were nonviraemic (adjusted mean difference of 10.1 fold after multiple regression analysis). The only other factor to influence significantly antibody level was genotype, where it was found that donors infected with type 1 showed 4 to 4.5 times greater serological reactivity by the Ortho assay than those infected with type 2 or 3. Antibody levels by the Ortho assay correlated closely to those detected by the Murex VK48 assay, and similar differences between PCR-positive and negative donors and between those infected with different genotypes were found. Differences in serological reactivity between genotypes indicate that a large proportion of epitopes of the type 1a or 1b recombinant proteins used in current assays are genotype specific. Variation in sensitivity of screening assays for different genotypes is of potential concern when used in countries where non-type 1 genotypes predominate in the blood donor or patient population.

Genetic variability of hepatitis C virus in South Egypt and its possible clinical implication

“…HCV genotype is an important predictor of response to interferon-alpha and ribavirin combination therapy [Hnatyszyn, 2005]. The route of transmission and serological reactivity are other factors which may differ among different HCV genotypes [Dhaliwal et al, 1996]. However, it is unclear, whether or not HCV genotypes differ in their pathogenicity [Zein, 2000].…”

Characteristics of Nucleotide Substitution in the Hepatitis C Virus Genome: Constraints on Sequence Change in Coding Regions at Both Ends of the Genome

“…At present, it is unclear whether these divergent subtypes should be considered as divergent subtypes of types 3 and 6 (Mellor et al 1995;Doi et al 1996;Mizokami et al 1996;Simmonds et al 1996), or as distinct virus types (Tokita et al 1994a(Tokita et al ,b, 1995(Tokita et al , 1996Sugiyama et al 1995). Evidence tacherjee et al 1995;Dhaliwal et al 1996) and sensitivity to interferon treatment (Davis 1994), but similar differences have not yet been demonstrated between virus subtypes.…”

Variability of the Hepatitis C Virus Genome

“…To estimate the genotype dependence of the sensitivity of the Ortho third generation assay, we compared antibody reactivity of samples collected from blood donors infected with genotypes 1, 2 and 3. Although antibody levels varied markedly between individuals, we found an approximate 5-fold reduction in median reactivity of type 2 and 3 samples in the ELISA [94], a difference in sensitivity that can be shown experimentally to substantially reduce the number of samples that can be detected on screening. On the basis of these results we are currently developing ELISAs based upon recombinant proteins from other genotypes, and comparing their effectiveness with conventional assays for blood donor screening of populations infected with predominantly non-type 1 variants.…”