Detection of the Hepatitis B Surface Antigen in Patients with Occult Hepatitis B by Use of 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.

Prevalence of occult hepatitis B virus infection in adults: a systematic review and meta-analysis

“…However, recent studies suggest that newer-generation, high-sensitivity HBsAg assays successfully detect additional cases of positive HBsAg in populations formally known to be negative for HBsAg. 32 In addition, although 138 studies included in our meta-analysis reported HBV NAT assay brand and model, we noted that often the reported assay sensitivity, if reported at all, was different to the assay sensitivity reported in the manufacturer's catalogue, and endemicity and population groups confounded analysis attempts based on LOD. Overall, it was impossible to reliably estimate the dual effect of HBsAg or NAT assay LOD on occult HBV infection prevalence, or perform an analysis with stricter inclusion criteria based on the LOD of assays.…”

The role of different viral biomarkers on the management of chronic hepatitis B

“…The lower limit of detection is around 0.05 IU/mL for most commonly used quantitative assays. [40][41][42] The clinical significance of measuring HBsAg by higher sensitivity assays with the lower limit of detection of 0.005 IU/mL and 0.0005 IU/mL [43][44][45][46] remains to be defined. Serum qHBsAg…”

Editorial: HBsAg seroclearance after pegylated interferon treatment—The beginning of the end

“…As it would not be feasible to biopsy every functionally cured patient, non‐invasive means to assess the risk of HBVr should be explored. More sensitive HBsAg assays 6 might be used to improve sensitivity, as well as novel viral biomarkers including serum hepatitis B core‐related antigen and HBV RNA; both are surrogate markers of cccDNA transcription, detected in ~15% of patients who developed spontaneous HBsAg seroclearance 7 …”