ARCHITECT Hepatitis C Virus Ag Research Articles

Diagnostic performance of hepatitis C core antigen assay to identify active infections: A systematic review and meta-analysis.

Hepatitis C virus (HCV) core antigen (HCVcAg) assay is an alternative for diagnosing HCV infection in a single step. This meta-analysis aimed to evaluate the Abbott ARCHITECT HCV Ag assay's diagnostic performance (validity and utility) for diagnosing active hepatitis C. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were searched until 10 January 2023. The protocol was registered at the prospective international register of systematic reviews (PROSPERO: CRD42022337191). Abbott ARCHITECT HCV Ag assay was the test for evaluation, and nucleic acid amplification tests with a cut-off ≤50IU/mL were the gold standard. Statistical analysis was performed using STATA with the MIDAS module and random-effects models. The bivariate analysis was conducted on 46 studies (18,116 samples). The pooled sensitivity was 0.96 (95% CI=0.94-0.97), specificity 0.99 (95% CI=0.99-1.00), positive likelihood ratio 141.81 (95% CI=72.39-277.79), and negative likelihood ratio 0.04 (95% CI=0.03-0.06). The area under the summary receiver operating characteristic curve was 1.00 (95% CI=0.34-1.00). For active hepatitis C prevalence values of 0.1%-15%, the probability that a positive test was a true positive was 12%-96%, respectively, indicating that a confirmatory test should be necessary, particularly with a prevalence ≤5%. However, the probability that a negative test was a false negative was close to zero, indicating the absence of HCV infection. The validity (accuracy) of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection in serum/plasma samples was excellent. Although the HCVcAg assay showed limited diagnostic utility in low prevalence settings (≤1%), it might help diagnose hepatitis C in high prevalence scenarios (≥5%).

Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.

The standard algorithm for diagnosing hepatitis C virus (HCV) infection has two steps, an HCV antibody test for screening and a nucleic acid amplification test (NAAT) for confirmation. However, the HCV core antigen (HCVcAg) detection assay is an alternative for one-step diagnosis. We aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay to detect active hepatitis C in serum/plasma in people living with HIV/AIDS (PLWHA), through a systematic review and meta-analysis. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched until 20 September 2022 (PROSPERO, CRD42022348351). We included studies evaluating Abbott ARCHITECT HCV Ag assay (index assay) versus NAATs (reference test) in PLWHA coinfected with HCV who did not receive antiviral treatment for HCV. Meta-analysis was performed with the MIDAS module using Stata and random-effects models. The QUADAS-2 tool evaluated the risk of bias. The bivariate analysis was conducted on 11 studies with 2,407 samples. Pooled sensitivity was 0.95 (95% CI = 0.92 to 0.97), specificity 0.97 (95% CI = 0.93 to 0.99), positive likelihood ratio 37.76 (95% CI = 12.84 to 111.02), and negative likelihood ratio 0.06 (95% CI = 0.04 to 0.09). The area under the curve was 0.97 (95% CI = 0.20 to 1.00). For low prevalence (≤5%), the posttest probability that an individual with a positive test was a true positive ranged from 4% to 67%, whereas, at high prevalence (≥10%), the posttest probability was between 81% and 87%, indicating that a confirmatory test should be necessary, particularly with prevalence values of ≤1%. Regardless of prevalence, the probability that an individual with a negative test was a false negative was close to zero, indicating that the individual was not infected with HCV. In conclusion, the accuracy of the Abbott ARCHITECT HCV Ag assay was very good for HCV screening in serum/plasma samples from PLWHA. The clinical utility to confirm HCV infection was acceptable in high-prevalence settings (≥10%) but poor in low-prevalence settings (≤1%). Furthermore, it was excellent in excluding active HCV infection.

Multicenter performance evaluation of the Elecsys HCV Duo immunoassay.

The diagnostic accuracy of the Elecsys® HCV Duo antigen-antibody combination immunoassay (Roche Diagnostics GmbH) was evaluated for the detection of hepatitis C virus (HCV) infection, versus commercially available comparators. This multicenter study (August 2020-March 2021) assessed the specificity of the Elecsys HCV Duo immunoassay and comparator assays in blood donor and routine clinical laboratory samples; sensitivity was determined in confirmed HCV-positive samples and seroconversion panels. The Elecsys HCV Duo immunoassay was compared with the Monolisa HCV Ag-Ab ULTRA V2, Murex HCV Ag/Ab Combination and ARCHITECT HCV Ag assays, as well as nucleic acid testing (NAT). The antibody (anti-HCV) module of the Elecsys HCV Duo immunoassay was compared with the Elecsys Anti-HCV II, Alinity s Anti-HCV, ARCHITECT Anti-HCV and RIBA HCV 3.0 SIA assays. The specificity of the Elecsys HCV Duo immunoassay was 99.94% (95% confidence interval [CI], 99.89-99.97) and 99.92% (95% CI, 99.71-99.99) in blood donor (n=20,634) and routine clinical laboratory samples (n=2531), respectively. The specificity of the Elecsys HCV Duo immunoassay was similar or better than comparator assays. The sensitivity of the Elecsys HCV Duo immunoassay in confirmed HCV-positive samples (n=257) was 99.6%. In seroconversion panels, the Elecsys HCV Duo immunoassay detected infections earlier (2.2-21.9 days) than all but one of the comparator assays and detected HCV 1.8 days later than NAT. The Elecsys HCV Duo immunoassay shows high diagnostic accuracy, reduces the diagnostic window, and could be used when NAT is not possible.

Evaluation of Hepatitis C Virus Core Antigen Assay in a Resource-Limited Setting in Pakistan.

The diagnosis of Hepatitis C virus (HCV) infection can be challenging due to its cost and a lack of access to centralized testing. There is an urgent need to develop simplified HCV testing algorithms. The aim of this study was to evaluate the performance characteristics of a Hepatitis C core antigen (HCVcAg) assay in a decentralized, resource-limited setting. This is a descriptive cross-sectional study from a highly endemic area of Karachi, Pakistan. Between October 2019 and July 2020, subjects aged 12 years and above who screened positive for HCV antibodies were simultaneously tested for HCV RNA (Xpert HCV Viral Load, GeneXpert® IV, Cepheid, France) and HCVcAg (ARCHITECT HCV Ag assay, Abbott® Diagnostics) to confirm active HCV infection. An Abbott ARCHITECT® i1000SR Immunoassay Analyser was installed at a local district hospital as a point-of-care (POC) facility for HCVcAg testing, while samples for HCV RNA were tested in a central lab. Two hundred individuals (mean age 46.4 ± 14.5 years, 71.5% females), who screened positive for HCV antibody, were included in the study. HCV RNA was detected in 128 (64.0%) while HCVcAg was reactive in 119 (59.5%) cases. Performance of the Immunoassay Analyser was excellent with a higher throughput and quicker readout value compared to the GeneXpert System. The sensitivity and specificity of HCVcAg (≥10 fmol/L) at HCV RNA thresholds of ≥12 was 99.1% (95% CI: 95–100%) and 87.6% (95%CI: 78.4–94%). A strong agreement was observed between the HCVcAg assay and HCV RNA. The ARCHITECT HCV Ag assay showed high sensitivity and specificity compared to HCV RNA in a decentralized, resource-limited setting. It can therefore be used as a confirmatory test in HCV elimination programs, particularly for low-income countries such as Pakistan.

Architect HCV Ag assay is an efficient alternative tool to RNA qRT-PCR quantification for assessing viral load in HCV infection

Objective To evaluate the performance characteristics of the automated Architect hepatitis C virus (HCV) core Ag assay versus HCV RNA by PCR among Egyptian patients and to assess its use for valuable clinical workup. Background HCV diagnosis by conventional anti-HCV assays has high rate of false positivity, false negativity, and a limited sensitivity for detection. Although HCV RNA assays are a reliable method for HCV diagnosis, they need technical skills and may also have false-positive results because of contamination. Moreover, the test is time consuming and more expensive. In contrast, the HCV core antigen test detects circulating HCV core antigen and identifies individuals who are actively infected with HCV. A commercialized test (the Architect HCV core antigen test) is supposed to have a sensitivity to detect ∼0.06 pg/ml and consequently a significant increase in sensitivity over the previous assay and a stronger correlation with HCV RNA testing. Patients and methods A descriptive, cross-sectional study was conducted on 60 HCV antibody-positive patients attending the outpatient clinic of Tropical Medicine Department, Al-Hussein University Hospital, Cairo, Egypt. The patients were classified into four groups based on the level of HCV viremia: group A included five patients with PCR below detection limit (12 IU/ml), group B included 39 patients with low viremia (<100 000 IU/ml), group C included 13 patients with moderate viremia (100 000–10 000 000 IU/ml), and group D included three patients with high viremia (>10 000 000 IU/ml). Each case was subjected to thorough clinical evaluation, HCV RNA quantification by Abbott Real Time HCV assay, and HCV Ag quantification by Architect HCV core antigen test. Results HCV Ag was found to be negative only in five of 55 HCV RNA-positive patients who had low level of viremia. The levels of HCV Ag showed a good correlation with those from the HCV RNA quantification (r=0.913, P≤0.001). Regarding HCV core antigen/HCV RNA ratio, it was not fixed for all patients. In most of them, each 1 pg/ml core Ag was equal to ∼10 000 IU/ml of RNA. Conclusion The Architect HCV Ag assay could be used as an alternative tool to HCV RNA PCR quantification in assessing viral load in HCV infection, and it has the advantages of lower cost, easy testing, and rapid reporting.

Community screening for hepatitis C virus infection in a low-prevalence population

BackgroundAge cohort screening for hepatitis C virus (HCV) might be an effective strategy if the majority of undiagnosed cases are concentrated in a particular age group. The objective of this study was to determine HCV prevalence in different age cohorts of the general population in the Central European part of Russia and second, to assess feasibility of HCV antigen testing for community screening programs.MethodsSera from 2027 volunteers were tested for anti-HCV (Architect Anti-HCV, Abbott Laboratories). All anti-HCV reactive samples were confirmed in an immunoblot and tested for HCV Ag (ARCHITECT HCV Ag, Abbott Laboratories), HCV RNA and HCV viral load.ResultsOut of 31 individuals with anti-HCV reactive result, 22 (71%) were confirmed by immunoblot, six were false positives and three were indeterminate. Active infection was observed in 73% of anti-HCV confirmed positives. Five out of 16 individuals had low HCV-RNA levels (< 10,000 IU/mL) and one of those had a very low level (594 IU/mL). Agreement between HCV Ag and HCV RNA was 100%. Total anti-HCV and active HCV infection rates were 1.09% (22/2027) and 0.79% (16/2027), respectively. The peak rates were observed in people 60 years or older (anti-HCV: 2.84% [95% CI: 1.66–4.74%], 13/319; HCV RNA/HCV Ag: 2.23% [95% CI: 1.20–4.00%], 10/319).ConclusionsOverall HCV prevalence is low, except in people 60 years or older. The latter should be considered as a target group for HCV screening. The high agreement between HCV RNA and HCV Ag suggests the utility of HCV Ag testing to confirm active infection in screening programs.

Hepatitis C virus core antigen for screening organ donors and recipients

Organ donors and recipients are routinely screened for hepatitis C virus (HCV) infection, typically via anti-HCV detection. We analyze the utility of an alternative HCV core antigen (HCV-Ag) quantification system, the ARCHITECT HCV Ag Assay, in this setting. We simultaneously tested 315 samples from potential organ donors and recipients using two chemiluminescent microparticle immunoassays: ARCHITECT Anti-HCV and HCV Ag (Abbott, Germany). HCV-Ag was detected in 81 of the serum samples (25.71%) and anti-HCV in 87 (27.62%). Seventy-five of the HCV-Ag–positive samples were positive for anti-HCV (92.59%). Overall concordance between the two assays was 94.29%. Of the six HCV-Ag–positive/anti-HCV–negative patients, five had HCV-Ag values <32 fmol/L, and the sixth had a concentration of 477.50 fmol/L (viral load, 137,000 IU/mL). The HCV AG Assay detects HCV infections missed by the Anti-HCV Assay. Both markers should be used to screen for HCV infection in potential organ donors and recipients.

Hepatitis C virus seroprevalence and prevalence of chronic infection in the adult population in Ireland: a study of residual sera, April 2014 to February 2016.

Robust data on hepatitis C virus (HCV) population prevalence are essential to inform national HCV services. In 2016, we undertook a survey to estimate HCV prevalence among the adult population in Ireland. We used anonymised residual sera available at the National Virus Reference Laboratory. We selected a random sample comprising persons ≥ 18 years with probability proportional to the general population age-sex distribution. Anti-HCV and HCV Ag were determined using the Architect anti-HCV and HCV Ag assays. Fifty-three of 3,795 specimens were seropositive (age-sex-area weighted seroprevalence 0.98% (95% confidence interval (CI): 0.73–1.3%)). Thirty-three specimens were HCV-antigen and antibody-positive (age-sex-area weighted prevalence of chronic infection 0.57% (95% CI: 0.40–0.81%)). The prevalence of chronic infection was higher in men (0.91%; 95% CI: 0.61–1.4%), in specimens from the east of the country (1.4%; 95%CI: 0.99–2.0%), and among persons aged 30–39 years and 40–49 years (1.1% (95% CI: 0.59–2.0%) and 1.1% (95% CI: 0.64–1.9%) respectively). Ireland ranks at the lower end of the spectrum of prevalence of chronic HCV infection internationally. Men born between 1965 and 1984 from the east of the country have the highest rate of chronic HCV infection.

Hepatitis C virus core antigen: A simplified treatment monitoring tool, including for post-treatment relapse

BackgroundSimple, affordable diagnostic tools are essential to facilitate global hepatitis C virus (HCV) elimination efforts. ObjectivesThis study evaluated the clinical performance of core antigen (HCVcAg) assay from plasma samples to monitor HCV treatment efficacy and HCV viral recurrence. Study designPlasma samples from a study of response-guided pegylated-interferon/ribavirin therapy for people who inject drugs with chronic HCV genotype 2/3 infection were assessed for HCV RNA (AmpliPrep/COBAS Taqman assay, Roche) and HCVcAg (ARCHITECT HCV Ag, Abbott Diagnostics) during and after therapy. The sensitivity and specificity of the HCVcAg assay was compared to the HCV RNA assay (gold standard). ResultsA total of 335 samples from 92 enrolled participants were assessed (mean 4 time-points per participant). At baseline, end of treatment response (ETR) and sustained virological response (SVR) visits, the sensitivity of the HCVcAg assay with quantifiable HCV RNA threshold was 94% (95% CI: 88%, 98%), 56% (21%, 86%) and 100%, respectively. The specificity was between 98 to 100% for all time-points assessed. HCVcAg accurately detected all six participants with viral recurrence, demonstrating 100% sensitivity and specificity. One participant with detectable (non-quantifiable) HCV RNA and non-reactive HCVcAg at SVR12 subsequently cleared HCV RNA at SVR24. ConclusionsHCVcAg demonstrated high sensitivity and specificity for detection of pre-treatment and post-treatment viraemia. This study indicates that confirmation of active HCV infection, including recurrent viraemia, by HCVcAg is possible. Reduced on-treatment sensitivity of HCVcAg may be a clinical advantage given the moves toward simplification of monitoring schedules.

INVESTIGATION OF THE SIGNIFICANCE OF DETECTION OF THE NUCLEOCAPSID ANTIGEN OF THE HEPATITIS C VIRUS IN CHILDREN WITH CHRONIC HEPATITIS C

The aim of this study was to investigate the clinical and diagnostic significance of the detection of core-antigen of hepatitis C virus (HCV) in children with chronic hepatitis C (CHC). Sera of 101 patients and 24 non-infected participants were analyzed. Core-antigen was determined by chemiluminescent method using «ARCHITECT HCV Ag» (Abbott, USA). HCV RNA was detected by highly sensitive OT-PCA. The presence of liver fibrosis was established by non-invasive methods. Antibody to core-antigen was detected by ELISA using commercial test-systems. A correlation was found between concentration of core-antigen and HCV RNA, viral subtypes, ALT level, and presence of liver fibrosis. High sensitivity and specificity of the chemiluminescent method for the detection of core antigen in children with CHC was shown. For the first time three ranges of core-antigen concentrations were proposed.

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

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. To evaluate the accuracy of diagnosis of active HCV infection among adults and children for 5 HCVcAg tests compared with NAT. EMBASE, PubMed, Web of Science, Scopus, and Cochrane Database of Systematic Reviews from 1990 through 31 March 2016. Case-control, cross-sectional, cohort, or randomized trials that compared any of 5 HCVcAg tests with an NAT reference standard. 2 independent reviewers extracted data and assessed quality using an adapted QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. 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. 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. 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. National Institutes of Health.

Probable hepatitis C virus transmission from a seronegative blood donor via cellular blood products.

Probable hepatitis C virus transmission from a seronegative blood donor via cellular blood products.

Clinical utility of the ARCHITECT HCV Ag assay for early treatment monitoring in patients with chronic hepatitis C genotype 1 infection

BackgroundVirologic response-monitoring is essential for determining therapy duration in patients with chronic hepatitis C virus (HCV) infection. This is usually performed using highly sensitive HCV-RNA assays. However, HCV-RNA assays are time-consuming, expensive and require highly trained personnel. Quantitative determination of HCV core-antigen (HCVAg) levels may be used to supplement treatment monitoring. ObjectivesThe clinical utility of the ARCHITECT HCV Ag assay (Abbott Diagnostics) for response-guided therapy was investigated. Study designWe analyzed serum from 160 patients with HCV genotype 1 infection who had been treated with peg-interferon alfa-2b/ribavirin. HCVAg levels were determined at baseline, weeks 1, 2, 4 and 12. HCVAg levels were compared to those obtained with HCV-RNA assays: VERSANT HCV Quantitative 3.0 (bDNA) and Qualitative (TMA, both Siemens Healthcare) assay and the Abbott RealTime HCV assay (ART; Abbott Diagnostics). ResultsBaseline HCVAg levels correlated well with HCV-RNA as assessed by bDNA (r=0.91; p<0.0001) and ART (r=0.92; p<0.0001), respectively. Patients with undetectable HCVAg levels at week 1 had a 90.9% probability (positive predictive value) to achieve a rapid virologic response (HCV-RNA undetectable at week 4) based on TMA and 86.4% based on ART, respectively. Patients with less than 1log10 reduction in HCVAg between baseline and week 12 had a 90% probability (negative predictive value) to achieve a nonresponse (<2log10 decline in HCV-RNA between baseline and week 12) based on bDNA and 100% based on ART, respectively. ConclusionsDetermination of HCVAg may be useful for antiviral response-monitoring in patients with HCV genotype 1 infection.

Is Hepatitis C Virus Core Antigen an Adequate Marker for Community Screening?

A new hepatitis C virus (HCV) core antigen (HCV Ag) assay was thought to have a good correlation with HCV RNA. The aim was to elucidate the usefulness of this HCV Ag assay in community screening. In a township where HCV is endemic, 405 residents aged 58 years or older responded to a follow-up community screening. All subjects were tested for anti-HCV (AxSYM, version 3.0; Abbott Diagnostics) and HCV Ag (Architect HCV Ag test; Abbott Diagnostics). For subjects with anti-HCV signal-to-cutoff ratios (S/CO) > 10 and/or HCV Ag > 3 fmol/liter, HCV RNA data (Taqman HCV RNA; Roche Diagnostics) were further checked. A total of 115 (28.4%) subjects had their serum HCV RNA levels measured, and 93 were HCV RNA positive. The other 290 subjects were supposed to be HCV RNA negative. HCV Ag was significantly correlated with HCV RNA according to the following equation: (log HCV RNA) = 2.08 + 1.03 (log HCV Ag) (R(2) = 0.94; P < 0.001). As determined using a combination of the values for anti-HCV (S/CO > 40) and HCV Ag (>3 fmol/liter) as a cutoff to predict viremia, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 96.8%, 100%, 99.3%, 100%, and 99%, respectively. In conclusion, for a community study, HCV Ag showed good correlation with HCV RNA. In addition, anti-HCV or HCV Ag can predict HCV viremia well, while a combination of anti-HCV (>40 S/CO) and HCV Ag (>3 fmol/liter) can provide the best result validity.

Evaluation of ARCHITECT HCV Core Antigen Assay

Hepatitis C virus (HCV) core antigen (Ag) levels are known to be well correlating with HCV RNA levels, and may be used as an alternative marker of HCV replication for monitoring the response to HCV treatment. However, the low sensitivity of HCV core Ag assay has been an obstacle for clinical use. In this study, recently developed ARCHITECT HCV Ag assay (Abbott Laboratories, USA) was evaluated for analytical performance and clinical usefulness. A total of 109 sera from HCV infected patients including various genotypes of HCV (1b, 2, 2a/2c, 2b, and 3a) and 20 sera from healthy donors were used for evaluating the sensitivity, precision, and linearity of the HCV core Ag assay. The cross reactivity with HIV, hepatitis B virus and myeloma proteins (N=5, each) and correlation with HCV RNA PCR assay were also evaluated. The sensitivity of the HCV core Ag assay was 97.2% (106/109) and there were no false positive results and cross reactivity. The within-run, between-run and between-day CVs were 3.0%, 2.5% and 3.0%, respectively. The levels of HCV core antigen showed a good correlation with those of HCV RNA quantification (r=0.940). The HCV Ag assay showed an excellent linearity in the range from 0.63 to 17,114 fmol/L (r=0.999). The ARCHITECT HCV Ag assay was good in sensitivity, precision, and linearity and its results well correlated with HCV RNA levels. This assay could be used as a good marker of viral replication for monitoring the therapy response in chronically HCV infected patients.