Hepatitis C Virus Core Mutations Associated with False-Negative Serological Results for Genotype 3a Core Antigen

Abstract

Genetic characterization of the genotype 3a (GT3a) hepatitis C virus (HCV) core region from HCV core antigen (HCVcAg)-negative/RNA-positive cases and HCVcAg-positive/RNA-positive controls identified significant associations between the substitutions A48T and T49A/P and failure to detect HCVcAg (P < 0.05). Polymorphisms at residues 48 and 49 in the core protein are present across all major epidemic and endemic GTs. These findings have implications for HCV diagnosis, particularly in low-income regions in which GT3a HCV is endemic.

Hepatitis C Virus Core Antigen: A Simplified Treatment Monitoring Tool, including for Post-Treatment Relapse

“…A48T mutation is present in all genotypes (range: 0.35-6.70%). T49A mutation is present in all genotypes (range: 0.1-4.50%), T49P is present in GT2 (as well as Gt1a, GT1b and GT4, range: 0.4-15.7%) [19]. Those mutations were detected in the subsequent time-points (week 4, SVR12 and FU1).…”

“…For screening HCV in low prevalence setting, a three step algorithm with HCV antibody, followed by HCVcAg (for HCV ab reactive result) and finally HCV RNA test (for HCVcAg non-reactive result) would be cost effective in achieving 100% detection of active viraemia as previously described [37]. This study also identified six genotype 3 participants for whom the HCVcAg assay was consistently negative and HCV RNA levels quantifiable, five of whom could be attributable to amino acids substitutions identified in Core region previously showed to affect HCVcAg serological result [19]. Little data on the prevalence of those mutations are known in the general population and more studies are required to assess the impact of false negative HCV detection due to core antigen mutations on all genotypes.…”

“…the "grey-zone") were retested per manufacturer recommendations where sample was available. For participants with quantifiable HCV RNA, and yet consistently negative HCVcAg results, the HCV Core gene was amplified and sequenced using previously published methods where sample was available [15,17] to identify potential mutations in the antibody binding region of the ARCHITECT HCV Ag assay [18][19][20].…”

Investigation of the Significance of Detection of the Nucleocapsid Antigen of the Hepatitis C Virus in Children With Chronic Hepatitis C

“…Ранее было показано влияние субтипов ВГС на соот-ношение вирусной РНК и core-антигена [22,23]. В на-стоящем исследовании это было изучено для доминирую-щих субтипов вируса у детей с ХГС (табл.…”

“…Самое высокое соотношение установлено для субти-па 3а, что подтверждается данными, полученными при анализе образцов взрослых пациентов [10,22,23].…”