Comparison of Serum HBsAg Quantitation by Four Immunoassays, and Relationships of HBsAg Level with HBV Replication and HBV Genotypes

Abstract

BackgroundThe decline in hepatitis B virus surface antigen (HBsAg) may be an early predictor of the viral efficacy of Hepatitis B virus (HBV) therapy. The HBsAg levels obtained by different immunoassays now need comparing and the relationships between levels of HBsAg and HBV DNA alongside HBsAg and genotype must be evaluated.Methodology/Principal FindingsHBsAg levels were compared among 80 patients using the Abbott Architect assay, a commercial immunoassay approved for HBsAg detection and quantitation, and three other assays derived from immunoassays approved for HBsAg detection (manufactured by Diasorin, Bio-Rad and Roche). Good correlation was found between the Abbot vs. Diasorin, Bio-Rad and Roche assays with narrow 95% limits of agreement and small mean differences: −0.06 to 0.11, −0.09 log10 IU/mL; −0.57 to 0.64, −0.04 log10 IU/mL; −0.09 to 0.45, −0.27 log10 IU/mL, respectively. These agreements were not affected by genotypes A or D. HBsAg was weakly correlated with HBV DNA, whatever the HBsAg assay used: Abbott, ρ = 0.36 p = 0.001, Diasorin ρ = 0.34, p = 0.002; Bio-Rad ρ = 0.37, p<0.001; or Roche ρ = 0.41, p<0.001. This relationship between levels of HBsAg and HBV DNA seemed to depend on genotypes. Whereas HBsAg (Abbott assay) tended to correlate with HBV DNA for genotype A (ρ = 0.44, p = 0.02), no such correlation was significant for genotypes D (ρ = 0.29, p = 0.15).Conclusion/SignificanceThe quantitation of HBsAg in routine clinical samples is comparable between the reference assay and the adapted assays with acceptable accuracy limits, low levels of variability and minimum discrepancy. While HBsAg quantitation is not affected by HBV genotype, the observed association between levels of HBsAg and HBV DNA seems genotype dependent.

Hepatitis B Virus Genotypes and Variants

“…A recent study evaluated the correlation between HBV DNA and HBsAg levels according to HBV genotype. These investigators found that serum HBsAg level tended to correlate with HBV DNA level for genotype A, but did not reach significant for genotype D (Tuaillon et al 2012). We recently followed 187 patients with chronic HBV infection for a median of 8 years.…”

Dried Blood Spot Tests for the Diagnosis and Therapeutic Monitoring of HIV and Viral Hepatitis B and C

“…This analytical sensibility is generally insufficient to meet the minimum requirements of European regulatory authorities and WHO (Lower limit of detection (LOD) < 4 IU/mL) (Chevaliez et al, 2014; World Health Organization [WHO], 2019). HBsAg laboratory tests have a sensitivity <0.1 IU/mL (Tuaillon et al, 2012), suggesting that even with a dilution factor of 10 or 20 times related to the elution step, the DBS testing may have a better sensitivity than HBsAg RDT. Systematic reviews have reported 98% sensitivity and 100% specificity for HBsAg screening on DBS compared to 88.9% sensitivity and 98.4% specificity using HBsAg RDT Lange et al, 2017a).…”

Introduction of an Automated System for the Diagnosis and Quantification of Hepatitis B and Hepatitis C Viruses

“…A new assay was developed for measuring HBV core-related antigen (HBcrAg), which consists of a core, e antigen (HBeAg), and the precore HBV proteins (22-kD precore fragment, amino acids 28-150); HBcrAg levels correlated well with HBV DNA levels [15]. A recent study showed that the serum HBcrAg concentration was related to the level of intrahepatic cccDNA [16]. Until recently, and for more than a decade, only 1 commercial qHBsAg assay was available [15].…”