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

Abstract

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 ≤50 IU/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%).

Performance of HCV core antigen and PCR testing in a predominantly genotype 3 population

“…Sensitivity (98.0%, CI: 95.4%-99.3%) and specificity (98.6% CI: 95.0%-99.8%) for HCVcAg in our study with a cut-off of ≥3 fmol/L, is consistent with other studies. 6 Another study from Pakistan, reported a lower sensitivity and specificity of 96.8% and 91.8% (95%, CI: 83%-97%) 7 at ≥3 fmol/L. While they reported the higher HCVcAg sensitivity at a threshold of ≥10 fmol/L (99.1%, CI: 95-100%).…”

Down-Classification of Hepatitis C Virus Diagnostics: Implications for Screening and Diagnosis

“…HCVcAg correlates well with HCV RNA levels ≥10 000 IU/mL and, thus, can detect viremia in the vast majority of persons with active HCV infection. A recent metanalysis of 46 studies using HCVcAg reported the assay to have high specificity and sensitivity for active HCV infection but suboptimal positive predictive value in low prevalence settings [ 16 ]. Nonetheless, this test may be a valuable addition to the rapid diagnostic armamentarium, especially in high-prevalence settings where nucleic acid testing is less feasible or unavailable [ 15 ].…”