Correlation of improved hepatitis B surface antigen detection limits with hepatitis B virus DNA nucleic acid test yield in blood donations

BACKGROUND: This study provides data on the quantitative relationship between hepatitis B surface antigen (HBsAg; ng/mL) and hepatitis B virus (HBV) nucleic acid test (NAT; copies/mL) and addresses whether HBsAg assays with improved sensitivity would impact the detection of HBV-positive samples from occult or early seroconversion window period infections. STUDY DESIGN AND METHODS: Plasma samples were tested with an HBsAg assay (PRISM, Abbott Laboratories; sensitivity, 0.08-0.1 ng/mL) and with two HBsAg research prototype assays: HBsAg Prototype 1 (sensitivity, 0.032-0.045 ng/mL) and HBsAg Prototype 2 (sensitivity, 0.009-0.017 ng/mL); NAT assays were used to determine HBV DNA copy levels. RESULTS: Samples from 10 hepatitis B seroconversion panels covering the ramp-up phase were utilized to examine the relationship between detection of HBsAg using improved assays and viral load using quantitative HBV DNA polymerase chain reaction. For these samples, detection at the HBsAg assay cutoff (sample-to-cutoff ratio, 1.0) corresponded to 206 copies/mL HBV DNA for the HBsAg Prototype 1 assay and 329 copies/mL for the PRISM HBsAg assay. Compared to the PRISM HBsAg and HBsAg Prototype 1 assays, the HBsAg Prototype 2 assay detected two additional samples of 32 HBV DNA-positive samples obtained from blood donors with occult HBV and one of seven from blood donors with early window period infections. CONCLUSION: Increased sensitivity HBsAg assays result in the detection of samples containing lower viral loads. Improvements in the analytic sensitivity of HBsAg prototype assays allow the detection of additional HBV DNA-positive samples from donors with window period or occult infections compared to PRISM HBsAg. Improved HBsAg assays should allow for incremental detection of HBV infection.