Performance evaluation of the ADVIA Centaur anti-HBe and HBeAg assays.
ABSTRACT Detection of HBeAg and anti-HBe is valuable for the evaluation and therapeutic management of hepatitis B infection.
To determine the clinical performance of the newly CE-approved(a) HBeAg and anti-HBe assays on the fully automated, random access ADVIA Centaur immunoassay system.
Patient samples collected at two sites were used to compare the ADVIA Centaur assays to Abbott AxSYM assays. Consensus of discordant results was reached using Roche Elecsys assays. Additionally, two well-characterized seroconversion panels were evaluated.
The ADVIA Centaur HBeAg assay sensitivity was 100% and specificity was 99.5%. The ADVIA Centaur anti-HBe assay sensitivity was 100% and the resolved specificity was 98.2%. Fewer samples required retesting with the ADVIA Centaur assays than with the AxSYM. In two well-characterized seroconversion panels, the ADVIA Centaur anti-HBe assay detected anti-HBe 20-25 days earlier than the AxSYM assay; the ADVIA Centaur and AxSYM HBeAg assays detected HBe reactivity on the same day.
The ADVIA Centaur HBeAg and anti-HBe assays demonstrated good sensitivity and specificity, and thus are suitable for clinical use. Their novel algorithms require reduced retesting, suggesting these assays may be more cost effective.
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ABSTRACT: Due to the lack of proof reading activity of hepatitis B virus (HBV) polymerase, mutation/variation of the viral sequence is frequently found during long term follow-ups. In the majority of children with chronic HBV infection, wild type HBV is the dominant viral strain during the natural course of chronic HBV infection. During long-term follow-up, HBV precore mutants developed spontaneously in approximately 10 to 24% of children before HBeAg seroconversion, and in around 50% of children after HBeAg seroconversion mutants. Occasionally, children may be infected primarily by mutant strains of HBV. Approximately 36% of children with fulminant hepatitis and 30% of children with acute hepatitis B were infected by precore mutants of HBV transmitted by their mothers or blood donors. In addition, after universal HBV vaccination, HBV surface gene variants emerge or are selected under the immune pressure generated by the host or by administration of hepatitis B immune globulin and hepatitis B vaccination. In HBV DNA positive children from four sequential surveys in Taiwan, the prevalence of hepatitis B surface gene a determinant mutants increased from 7.8% before the vaccination program, to 19.6%, 28.1%, and 23.1% at 5, 10, and 15 years after the program. Nucleoside analogue may also induce mutant strains, which reduces the antiviral effects. The most common example is the YMDD mutation of the HBV polymerase gene after antiviral therapy with lamivudine. It developed in 19% of the treated children. In conclusion, children may be infected primarily by mutant strains of HBV either naturally during acute HBV infection. Those infected with wild type HBV initially may develop mutant strains gradually during the course of chronic infection under the host immune pressure. Vaccine escape mutants may develop after immunoprophylaxis. In addition, antiviral therapy with nucleoside anlogues may also induce drug resistant mutant strains. Understanding the viral mutation status will help to design accurate strategies of immunoprophylaxis and antiviral therapy against HBV infection.The Indian Journal of Pediatrics 08/2006; 73(9):803-807. DOI:10.1007/BF02790390 · 0.92 Impact Factor
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ABSTRACT: Human hepatitis B virus (HBV) can cause acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HBV e antigen (HBeAg), a secreted protein and not required for viral replication, is thought to play an immunoregulatory role during viral infection. However, the functional involvement of HBeAg in host immune response has not been fully elucidated. We report in this study that HBeAg can bind to interleukin-1 receptor accessory protein (IL-1RAcP). Interleukin-1 (IL-1) plays an important role in inflammation and regulation of immune response, and membrane form of IL-1RAcP (mIL-1RAcP) is an essential component of trimeric IL-1/IL-1 receptor/mIL-1RAcP complex. We show that glutathione S-transferase- or polyhistidine-tagged recombinant HBeAg can interact with endogenous mIL-1RAcP in vitro. Purified (His)6-HBeAg added in the culture medium can interact with overexpressed FLAG-tagged mIL-1RAcP in vivo. Indirect immunofluorescence and confocal microscopy show that HBeAg colocalizes with mIL-1RAcP on the cell surface. Furthermore, HBeAg is able to induce the interaction of IL-1 receptor I (IL-1RI) with mIL-1RAcP and trigger the recruitment of adaptor protein myeloid differentiation factor 88 (MyD88) to the IL-1RI/mIL-1RAcP complex. Assembly and activation of IL-1RI/mIL-1RAcP signaling complex by HBeAg can activate downstream NF-kappaB pathway through IkappaB degradation, induce NF-kappaB-dependent luciferase expression, and induce the expression of IL-1-responsive genes. Silencing of IL-1RAcP by small interfering RNA dramatically abolishes HBeAg-mediated NF-kappaB activation. These results demonstrate that HBeAg can trigger host IL-1 response by binding to mIL-1RAcP. The interaction of HBeAg with mIL-1RAcP may play an important role in modulating host immune response in acute and chronic HBV infection.Journal of Biological Chemistry 12/2006; 281(45):34525-36. DOI:10.1074/jbc.M510981200 · 4.60 Impact Factor
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ABSTRACT: The following article reports on newly developed ADVIA Centaur immunoassays (Bayer HealthCare LLC, Diagnostics Division; Tarrytown, NY, USA) for the detection of markers of hepatitis B infection in human serum and plasma. These fully automated assays detect antibodies to hepatitis B surface antigen (anti-HBs), total antibodies to hepatitis B core antigen (anti-HBc Total) and IgM antibodies to hepatitis B core antigen (anti-HBc IgM). The ADVIA Centaur HBV assays employ magnetic particle separation technology with direct chemiluminescence for optimal assay performance. The three ADVIA Centaur HBV assays were tested in extensive performance evaluations at two sites in Europe. Prospectively collected specimens from HBV infected subjects, blood donors, hospitalized/clinical patients and HBV vaccinees were tested under routine laboratory conditions to generate performance data. The studies resulted in the following clinical performance: overall diagnostic specificity > 99.9%, i.e. 100% for ADVIA Centaur Anti-HBs, 100% for ADVIA Centaur HBcIgM and 99.94% for ADVIA Centaur HBc Total. All of the assays showed excellent diagnostic sensitivity, as follows: 99.0% for ADVIA Centaur Anti-HBs, 98.5% for ADVIA Centaur HBcIgM and 100% for ADVIA Centaur HBc Total. Interfering substances and potential cross-reacting samples produced no effects on the results in any of the three ADVIA Centaur HBV assays. Evaluations using HBV seroconversion panels resulted in comparable or better results as compared to the reference assay(s). The performance evaluation data clearly demonstrate that the three ADVIA Centaur HBV assays are specific and sensitive automated immunoassays for the detection of antibodies to hepatitis B virus. Furthermore, these data indicate that assay performance is comparable, if not better, than the performance of currently marketed assays. Additionally, these assays have all of the advantages of being on the ADVIA Centaur immunoassay system including high throughput and full automation. Finally, these data, which had been submitted to the appropriate regulatory agencies (Notified Bodies) in Europe, have resulted in these assays now being CE marked and, thus, being readily available in the European market.Journal of Clinical Virology 04/2004; 30 Suppl 1:S6-10. DOI:10.1016/j.jcv.2004.02.003 · 3.47 Impact Factor