Detection of the hepatitis B surface antigen in patients with occult hepatitis B using an assay with enhanced sensitivity

Abstract

Patients with occult hepatitis B infection (OBI) have undetectable hepatitis B surface antigen (HBsAg) by conventional assays but detectable hepatitis B virus (HBV) DNA in blood/liver. We evaluated the key performance characteristics of a sensitive HBsAg assay (ARCHITECT HBsAg Next Qualitative Assay, referred as NEXT) with respect to HBsAg detection. Assay precision, sample carryover and seroconversion sensitivity of NEXT were evaluated. HBsAg was measured by NEXT in 1,138 individuals, including 1,038 patients who attended liver clinics in a tertiary hospital (200 HBV DNA-positive blood donors whose HBsAg was undetectable by conventional assays, and 38 patients receiving immunosuppressive therapy, 800 chronic hepatitis B patients with HBsAg seroclearance) and 100 HBsAg-negative subjects recruited from a community project. The within-run and within-laboratory coefficients of variation were <6% for the positive sample pools. In 9 seroconversion panels tested, NEXT allowed an earlier HBsAg detection than conventional assays. NEXT detected HBsAg in 10/200 (5%) HBsAg-negative blood donors, 1/20 (5%) and 0/18 HBsAg-negative patients with and without HBV reactivation respectively, and 59/800 (7.3%) patients with HBsAg seroclearance. HBsAg was detectable by NEXT in 27.8%, 8.2%, 6.9%, 3.8% and 1.9% samples at <3, 3–5, >5–8, >8–11, and >11 years after HBsAg seroclearance, respectively. Seven out of 100 HBsAg-negative community identified subjects was tested positive by NEXT. Comparing with conventional HBsAg assays, NEXT demonstrated a higher sensitivity and conferred an increment of 5–7% detection rate in patients with OBI, thereby helping in identifying HBV carriers and prevention of OBI-associated HBV transmission and reactivation.