Sensitivity of HCV core antigen and HCV RNA detection in the early infection phase

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Abstract
BACKGROUND : Various countries have introduced HCV NAT to exclude infectious donations collected during the preseroconversion window phase (PWP). For the same purpose, an ELISA has also been developed to detect HCV core antigen (cAg). STUDY DESIGN AND METHODS : Using sequential samples from regular plasma donors with very recent HCV infections, a total of 494 samples from 52 anti‐HCV‐negative donors were collected. These panels were used for direct comparison of the performance of PCR and ELISA in detecting viral markers (RNA and cAg) during the PWP of HCV infection. The panels were genotyped, and each sample was analyzed by qualitative and quantitative HCV PCR and by cAg ELISA. The HCV RNA doubling time was calculated from quantitation of viral RNA in consecutive samples during the earliest outbreak of viremia. RESULTS : Concurrent detection of HCV RNA and cAg in 218 and nondetection in 185 samples yielded 81.6‐percent concordance in the results of 494 samples. Unidirectional discrepancy of results (i.e., PCR positive and cAg negative) was seen in 91 of 494 (18.4%) samples, which was consistent with 65 specimens with RNA concentrations ranging between 300 and 100,000 IU per mL and 26 specimens with less than 300 IU per mL (limit of quantitative PCR). Individual genotyped panels had different kinetics and courses of viremia. The mean doubling time in the early PWP at the onset of viremia was derived to be 10.8 (range, 5.8‐21.0) hours. CONCLUSION : A majority of HCV RNA‐positive samples were also cAg‐positive during the PWP. The current cAg detection corresponds to 100,000 IU per mL of HCV RNA. Since low‐titer samples would be identified only by single‐donation NAT, which is often affordable only in developed countries, the cAg ELISA could offer a practical alternative for some countries. The doubling time for HCV RNA at the onset of viremia corresponds to a calculated mean delay of cAg detection during the virus burst phase of 2 or 5 days, when compared with minipool (5000 IU/mL) or single‐donation NAT (50 IU/mL), respectively.