A novel decentralized rapid test for detection of HCV antigens using smart polymer technology: a prospective multinational study.

Abstract

There is an unmet need for a rapid, affordable, and highly sensitive point-of-care HCV antigen test suitable for decentralized settings. We developed SMART-C, a lateral-flow assay integrating a thermo-responsive smart polymer for HCV antigen extraction and enrichment with colloidal gold nanoparticles. We evaluated its diagnostic performance against the Cobas® 6800 HCV RNA PCR assay as the reference standard. A multinational, multicentre, prospective diagnostic accuracy study was conducted during 2022-2026 at hospital and field sites in Egypt, Pakistan, and Japan. Paired serum/plasma samples from venous blood were tested blindly using SMART-C and quantitative HCV RNA PCR. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) were calculated following STARD guidelines. Additionally, 21 patients initiating direct-acting antiviral (DAA) therapy were prospectively followed to assess SMART-C performance during treatment and after viral clearance. Among 1,353 paired samples from a high-risk clinical cohort, SMART-C demonstrated 94.6% sensitivity (474/501; 95% CI, 92.3-96.3) and 91.3% specificity (778/852; 95% CI, 89.2-93.0), with 92.5% accuracy, 86.5% PPV, and 96.6% NPV. Agreement with PCR was high (κ=0.843). SMART-C paralleled PCR-defined viral decline during DAA therapy and became negative concordantly with PCR clearance in 19/21 patients. SMART-C achieved an analytical limit of detection below 10 IU/mL, approaching that of the Cobas® 6800 PCR assay (∼10 IU/mL). Its high diagnostic performance and simple lateral-flow format support its potential for decentralized HCV testing and contribution to WHO hepatitis C elimination goals.