Detection of hepatitis C core antigen in serum or plasma as a marker of hepatitis C viraemia in the serological window‐phase

Abstract

A new immunoassay for the detection of hepatitis C core antigen (HCVcoreAg) in peripheral blood during serological window-phase was evaluated among healthy blood donors, commercially available hepatitis C virus (HCV) seroconversion panels and in-house specimens from individuals undergoing seroconversion. Among 1964 low-risk blood donor samples, seven samples were initially reactive but only one was repeat reactive. Reactivity of this specimen was not confirmable by neutralization with specific anti-HCV core antibody, and the sample was negative for HCV RNA by polymerase chain reaction (PCR). The specificity of the HCVcoreAg enzyme-linked immunosorbent assay (ELISA) was 99.95%. In seven commercially available HCV seroconversion panels, HCVcoreAg appeared 23-46 days earlier than anti-HCV antibody by third generation assay. Additional testing with specimens from patients undergoing anti-HCV seroconversion indicated that HCVcoreAg becomes undetectable by the present test format soon after the onset of antibody. This test may be considered as an alternative to nucleic amplification techniques (NAT) for blood donor HCV screening. Additional development of technology for detecting HCVcoreAg may be useful for patient diagnosis and therapy monitoring.

Direct Binding of Hepatitis C Virus Core to gC1qR on CD4+and CD8+T Cells Leads to Impaired Activation of Lck and Akt

“…Free core protein, which is not associated with immune complexes or with virus particles, is especially detectable in the serologically negative window phase; the detection of total core protein (i.e., core-immune complex) in serum or plasma serves as an indirect marker for HCV replication and viremia (2,43). The amount of free core protein does not seem to be large in chronically infected patients and may not be sufficient for eliciting the immunosuppressive effect.…”

“…Furthermore, dendritic cell maturation and, correspondingly, their CD4 ϩ -T-cellpriming ability are impaired by the HCV core, leading to a defect in the induction of anti-HCV T cells (36,37). Importantly, free core protein (non-virion associated) is secreted from infected cells and is detectable in the bloodstream of HCV-infected patients, possibly providing the virus with an indirect means of affecting host immunity (2,25,26,43). This free core protein has been shown to interfere with both proliferation and effector activities of human T cells through its interaction with a complement receptor, gC1qR, in a mixedlymphocyte reaction (18,44,45,46).…”

Kinetics and Significance of Serum Hepatitis C Virus Core Antigen in Patients with Acute Hepatitis C

“…Attempts to identify predictive markers of progression to chronic infection have been largely unsuccessful, and the persistently or intermittently positive identification of HCV RNA by PCR is currently accepted as evidence of chronic evolution even when liver enzymes, such as alanine aminotransferase (ALT), return to within the normal range after acute onset (2). Recently, a new immunoassay for the detection of circulating HCV core antigen has been developed that may be useful for identifying acute HCV infection earlier than anti-HCV seroconversion, which is occasionally delayed by several weeks after onset (5,11). The assay performance seems excellent, with a 99.9% specificity and a sensitivity relative to nucleic acid testing (NAT) of 98.6% (7) and with a statistically significant positive correlation with HCV RNA levels (9).…”

Correspondências

“…As principais dificuldades para a implantação do NAT em doadores de sangue têm sido a logística, alto custo e problemas de contaminação das amostras 4 .…”