Background Diagnosis of chronic hepatitis C virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid testing (NAT). Testing for hepatitis C virus core antigen (HCVcAg) is a potential alternative to NAT. Purpose To evaluate the accuracy of diagnosis of active HCV infection among adults and children for 5 HCVcAg tests compared with NAT. Data sources EMBASE, PubMed, Web of Science, Scopus, and Cochrane Database of Systematic Reviews from 1990 through 31 March 2016. Study selection Case-control, cross-sectional, cohort, or randomized trials that compared any of 5 HCVcAg tests with an NAT reference standard. Data extraction 2 independent reviewers extracted data and assessed quality using an adapted QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. Data synthesis 44 studies evaluated 5 index tests. Studies for the Abbott ARCHITECT HCV Ag assay had the highest quality, whereas those for the Ortho HCV Ag enzyme-linked immunosorbent assay (ELISA) had the lowest quality. From bivariate analyses, the sensitivity and specificity of the assays were as follows: Abbott ARCHITECT, 93.4% (95% CI, 90.1% to 96.4%) and 98.8% (CI, 97.4% to 99.5%); Ortho ELISA, 93.2% (CI, 81.6% to 97.7%) and 99.2% (CI, 87.9% to 100%); and Hunan Jynda Bioengineering Group HCV Ag ELISA, 59.5% (CI, 46.0% to 71.7%) and 82.9% (CI, 58.6% to 94.3%). Insufficient data were available for a meta-analysis about the Fujirebio Lumipulse Ortho HCV Ag and Eiken Lumispot HCV Ag assays. In 3 quantitative studies using Abbott ARCHITECT, HCVcAg correlated closely with HCV RNA levels greater than 3000 IU/mL. Limitations Insufficient data were available on covariates, such as HIV or hepatitis B virus status, for subgroup analyses. Few studies reported genotypes of isolates, and data for genotypes 4, 5, and 6 were scant. Most studies were conducted in high-resource settings and reference laboratories. Conclusion The HCVcAg assays with signal amplification have high sensitivity, high specificity, and good correlation with HCV RNA levels greater than 3000 IU/mL and have the potential to replace NAT in settings with high HCV prevalence. Primary funding source National Institutes of Health.

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Hepatitis C Core Antigen Testing for Diagnosis of Hepatitis C Virus Infection: A Systematic Review and Meta-analysis

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UK Standards for Microbiology Investigations

Diagnosis of chronic hepatitis C virus (HCV) infection usually requires both a positive HCV antibody screen and confirmatory nucleic acid testing (NAT). This systematic review of 44 studies evaluat...

Hepatitis C Core Antigen Testing for Diagnosis of Hepatitis C Virus Infection

Screening tests for blood donations are based upon sensitivity, cost-effectiveness and their suitability for high-throughput testing. Enzyme immunoassay (EIAs) for hepatitis C virus (HCV) antibodies were the initial screening tests introduced. The "first generation" antibody EIAs detected seroconversion after unduly long infectious window period. Improved HCV antibody assays still had an infectious window period around 66 d. HCV core antigen EIAs shortened the window period considerably, but high costs did not lead to widespread acceptance. A fourth-generation HCV antigen and antibody assay (combination EIA) is more convenient as two infectious markers of HCV are detected in the same assay. Molecular testing for HCV-RNA utilizing nucleic acid amplification technology (NAT) is the most sensitive assay and shortens the window period to only 4 d. Implementation of NAT in many developed countries around the world has resulted in dramatic reductions in transfusion transmissible HCV and relative risk is now < 1 per million donations. However, HCV serology still continues to be retained as some donations are serology positive but NAT negative. In resource constrained countries HCV screening is highly variable, depending upon infrastructure, trained manpower and financial resource. Rapid tests which do not require instrumentation and are simple to perform are used in many small and remotely located blood centres. The sensitivity as compared to EIAs is less and wherever feasible HCV antibody EIAs are most frequently used screening assays. Efforts have been made to implement combined antigen-antibody assays and even NAT in some of these countries.

Current testing strategies for hepatitis C virus infection in blood donors and the way forward.

The object of this study was to develop a simple, rapid, specific, and highly sensitive method to detect HCV core antigen. A nucleic acid aptamer was designed with the high specificity and sensitivity in a nucleic acid lateral flow strip to compete with HCV core antigen and DNA probes. The lower detection limit of the test strip was calculated to be 10 pg/mL with the scanner and 100 pg/mL with naked eyes. Results showed that there were no cross-interactions with other proteins such as HCV NS3, E1/E2 antigens, HIV p24 antigens, or BSA proteins (HCV unrelated protein). When the viral load exceeded 104 copies/mL, the positive coincidence rates of ELISA and strip detection, when compared with the HCV RNA assay, were 98.44% and 97.28%, respectively. The results indicated that the ELISA detection and strip assay were in good agreement with the measured value. The results indicated that a nucleic acid lateral flow strip was a simple, rapid, specific, highly sensitive, and cost-effective field-based method for de...

Development Of A Nucleic Acid Lateral Flow Strip For Detection Of Hepatitis C Virus (Hcv) Core Antigen

Diagnosis and monitoring of hepatitis C virus (HCV) infection relies mainly on the detection of HCV antibodies and HCV RNA. HCV antibody test has a longer window period and is not applicable in the immunosuppressed population. Although HCV RNA test reduces the window period, it is still not widely recommended because of its high cost and requirement of specific equipment. HCV core antigen is another direct virological marker which has been investigated in recent years. HCV core antigen assay is as simple as the HCV antibodies assay and can detect HCV infection only 1 day delay compared to the HCV RNA assay. In order to evaluate the application of HCV core antigen test in HCV diagnosis and management, we performed this meta-analysis. Twenty five articles were finally included in meta-analysis. All statistical analyses were performed with MetaDisc 1.4 and Stata 11.0. The pooled sensitivity of HCV core antigen assay was 0.84 (95 % CI, 0.83-0.85), and the pooled specificity was 0.98 (95 % CI, 0.97-0.98). HCV core antigen assays may not displace HCV RNA assays to be a definitive diagnosis of HCV infection until now. Considering the higher sensitivity (0.926) and specificity (0.991) of subgroup, HCV-cAg detection is a promising method as a confirmatory test for HCV antibody positive, therapy-naive individuals. Explored by meta-regression and subgroup analysis, possible sources of heterogeneity of specificity was found, while the heterogeneity of sensitivity was still significant.

Core antigen tests for hepatitis C virus: a meta-analysis

High-quality cadmium selenide (CdSe) quantum dots (QDs) were synthesised in liquid paraffin with a mixture of octadecylamine and trioctylphosphine oxide as stabilising ligands. The synthesised CdSe QDs were characterised by ultraviolet–visible absorption and photoluminescence spectroscopy, transmission electron microscopy and selected area electron diffraction techniques. Compared with CdSe QDs synthesised in liquid paraffin stabilising with only oleic acid, CdSe QDs synthesised by this new route possess higher quantum yields, more symmetric and narrower emission spectra. The new route enables us to achieve high-quality CdSe QDs in less expensive solvent, liquid paraffin.

Shuijun Gu

Papers

Core antigen tests for hepatitis C virus: a meta-analysis

Synthesis and photoluminescence properties of high-quality CdSe quantum dot in liquid paraffin