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

Abstract

Background Diagnosis of chronic Hepatitis C Virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid test (NAT). HCV core antigen (HCVcAg) is a potential alternative to NAT. Purpose This systematic review evaluated the accuracy of diagnosis of active HCV infection among adults and children for five HCVcAg tests compared to NAT. Data Sources EMBASE, PubMed, Web of Science, Scopus, and Cochrane from 1990 through March 31, 2016. Study Selection Cohort, cross-sectional, and randomized controlled trials were included without language restriction Data Extraction Two independent reviewers extracted data and assessed quality using an adapted Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data Synthesis 44 studies evaluated 5 index tests. Studies for the ARCHITECT had the highest quality, while those for Ortho ELISA were the lowest. From bivariate analyses, the sensitivity and specificity with 95% CI were: ARCHITECT 93.4% (90.1, 96.4) and 98.8% (97.4, 99.5), Ortho ELISA 93.2% (81.6, 97.7) and 99.2% (87.9, 100), and Hunan Jynda 59.5% (46.0, 71.7) and 82.9% (58.6, 94.3). Insufficient data were available for a meta-analysis for Lumipulse and Lumispot. In three quantitative studies using ARCHITECT, HCVcAg correlated closely with HCV RNA above 3000 IU/mL. Limitations There was insufficient data on covariates such as HIV or HBV status for sub-group analyses. Few studies reported genotypes of isolates and there were scant data for genotypes 4, 5, and 6. Most studies were conducted in high resource settings within reference laboratories. Conclusions HCVcAg assays with signal amplification have high sensitivity, high specificity, and good correlation with HCV RNA above 3000 IU/mL. HCVcAg assays have the potential to replace NAT in high HCV prevalence settings.

Hepatitis C Virus Core Antigen: A Simplified Treatment Monitoring Tool, including for Post-Treatment Relapse

“…The findings of this study supports previous cross-sectional and analytical studies [9], suggesting that HCVcAg may be an affordable method to screen and diagnose large numbers of people with chronic HCV. Considering greater than 95% of those with chronic HCV Fig.…”

“…This study is the first to prospectively evaluate the clinical performance of HCVcAg in plasma to monitor HCV treatment and viral recurrence among an international cohort of recent PWID and people receiving OST with chronic HCV infection. While limited to genotype 2/3 HCV infection, this study supports previous studies indicating HCVcAg can be used to identify active HCV infection at baseline/screening among those with chronic HCV infection [9,[21][22][23] and identify those with a sustained virological response at 12 weeks post treatment [10,24]. While these data confirm a previous study by Chevaliez et al [10] that HCVcAg can accurately detect viral recurrence 12 or 24 weeks post-treatment, this study provides additional comprehensive longitudinal profiles from individuals with recurrent viraemia.…”

“…HCV RNA results were dichotomized based on two thresholds, including the quantification threshold (15 IU/mL; i.e., ≥15 IU/mL: "quantifiable" < 15 IU/mL: "non-quantifiable"), and a threshold at 3,000 IU/mL. The latter threshold was used given that it has been recently identified in a meta-analysis for high sensitivity, high specificity and good correlation with HCVcAg [9]. All data was analysed using Stata (Stata 14, StataCorp, College Station, USA) and displayed using Prism (Prism 6, GraphPad Software, San Diego, USA).…”

“…Several commercial HCVcAg assays are now available and have demonstrated highly sensitive and specific diagnoses of active HCV infection in a range of populations [9]. Despite extensive evaluation as a diagnostic tool for chronic HCV infection, fewer studies have evaluated the clinical utility of the HCVcAg assay to monitor HCV treatment outcomes [10][11][12][13].…”

The hepatitis C cascade of care in people who inject drugs in Dar es Salaam, Tanzania

“…First, HCV core antigen quantification (HCVcAg), which is a surrogate measure of HCV RNA, has a relatively low cost (at US$10 per test),25 with a fully automated assay available on the Abbott ARCHITECT ® platform. It has been recently validated in African resource‐limited settings and has been proposed as a one‐step diagnostic alternative to conventional screening in such an environment 26, 27, 28. An additional challenge to testing PWID is poor venous access.…”