Clinical Performance Evaluation of Four Automated Chemiluminescence Immunoassays for Hepatitis C Virus Antibody Detection

Abstract

Various automated chemiluminescence immunoassay (CLIA) analyzers for the detection of antibodies to hepatitis C virus (HCV) are now commercially available in clinical laboratories and are replacing conventional enzyme immunoassays. We investigated the performance of four anti-HCV CLIAs (the Architect Anti-HCV assay on the Architect i2000 system, the Vitros Anti-HCV assay on the Vitros ECiQ Immunodiagnostic System, the Access HCV Ab PLUS assay on the UniCel DxI 800 analyzer, and the newly developed Elecsys Anti-HCV assay on the Cobas e 411 analyzer). The total percent coefficient of variation values of imprecision were 3.5 to 5.7% with positive control materials and 7.2 to 10.2% with negative control materials. The agreement between the results of the Elecsys, Architect, Vitros, and Access CLIAs ranged from 94.5 to 98.1%. The clinical sensitivity of all CLIAs was 100%. Each CLIA showed excellent reproducibility and clinical sensitivity. The Elecsys, Architect, Vitros, and Access CLIAs showed clinical specificities of 98.2, 98.8, 96.5, and 98.2%.Hepatitis C virus (HCV), first identified in 1989, is an enveloped positive-strand RNA virus classified in the Hepacivirus genus in the family Flaviviridae (6). The HCV genome is about 9.5 kb in length and encodes 3,011-to 3,033-amino-acid polypeptides in structural and nonstructural regions (20). The structural region contains the core protein and two envelope proteins (E1 and E2), and nonstructural proteins have been assigned protease (NS2, NS3, and NS4A), helicase (NS3), and RNA-dependent RNA polymerase (NS5B) (21) functions.The first commercially available anti-HCV enzyme immunoassay (EIA) used a single HCV recombinant antigen derived from the nonstructural NS4 protein designated c100-3 (19). The sensitivity of this first-generation EIA was low for a highprevalence population (approximately 80%) and showed a high false-positive rate (up to 70%) in a low-prevalence blood donor group (13). Therefore, a second-generation EIA was developed and approved for use by the Food and Drug Administration (FDA) in 1992 (3). The second-generation EIA, which contained additional HCV antigens from the core (c22-3) and NS3 (c33c) proteins, showed increased sensitivity and specificity and shortened the average seroconversion period from 16 to 10 weeks (1, 3, 13, 18). The third-generation EIA, which added a fourth antigen (NS5), showed significantly improved performance, particularly for high-risk patients (2, 8). However, a residual risk still exists due to the seroconversion period of approximately 56 days, and high false-positive rates were not resolved (12). The Centers for Disease Control and Prevention (CDC) recommended that an anti-HCV screening test positive result be verified by a more specific supplemental assay such as recombinant immunoblot or nucleic acid test (5). To facilitate the use of the supplemental assay, the revised guideline included an option for reflex supplemental testing based on signal-to-cutoff (s/co) ratios (4).Today, automated chemiluminescence immunoassay (...

Multicenter evaluation of a fully automated third-generation anti-HCV antibody screening test with excellent sensitivity and specificity

“…This was equivalent to the rates obtained with the Architect Anti-HCV, the ADVIA Centaur Anti-HCV, and the Vitros Eci aHCV assays. These findings are consistent with the results from other studies in which the specificity of the Elecsys Anti-HCV assay was compared with the Architect Anti-HCV, the ADVIA Centaur HCV, and Vitros Eci aHCV assays [11][12][13][14].…”

Detection limit of architect hepatitis C core antigen assay in correlation with HCV RNA, and renewed confirmation algorithm for reactive anti-HCV samples

“…Several studies have been conducted to compare HCV RNA and HCV-Ag measurements in detecting an active hepatitis C earlier than with anti-HCV antibodies alone. The first generation of HCVAg became positive when HCV RNA was >10 4 IU/mL [13,14]. Newer assays, such as Abbott Architect based on chemiluminescence, have become available since then.…”

Diagnosis and Management of Hepatitis C Virus Infection

“…[57][58][59] These immunoanalyzers are fully automated and optimized for efficiency and throughput. Most of these platforms use a chemiluminescent readout, which provides higher sensitivity than other detection approaches.…”