Diagnostic Accuracy of Chemiluminescent Immunoassays Compared to Nucleic Acid Testing for Hepatitis C Screening in Blood Donors: A Systematic Review

Hepatitis C virus (HCV) remains a major global public health problem, requiring accurate and scalable diagnostic methods for effective screening and disease control. Nucleic acid testing (NAT) is considered the reference standard for HCV detection but is limited by high cost and technical complexity, particularly in resource-limited settings. Chemiluminescent immunoassays (CLIA) offer operational advantages and are increasingly used as alternative diagnostic tools. This systematic review was conducted following PRISMA guidelines to compare the diagnostic accuracy of CLIA with NAT for HCV detection in blood donors. A comprehensive literature search was performed in PubMed, Scopus, Web of Science, and Ebscohost for studies published between 2015 and July 2025. Eligible studies directly compared CLIA-based assays with NAT and reported sensitivity and specificity data. Study quality was assessed using the QUADAS-2 tool, and results were synthesized narratively. Four studies involving diverse populations and laboratory settings were included. CLIA-based assays demonstrated high diagnostic performance, with sensitivity ranging from 92.4% to 100% and specificity from 88.8% to 100% when compared with NAT. Several studies reported strong agreement between CLIA and molecular methods, supporting CLIA’s effectiveness for large-scale screening applications. CLIA provides a reliable and cost-effective alternative to NAT for HCV screening, particularly in blood donor and resource-limited settings. However, reduced sensitivity at low viral loads and study heterogeneity remain important limitations.