Molecular and Clinical Characteristics of Hepatitis B Surface Antigen

HBs protein is encoded by the pre-S and S genome, and the detection of HBs antigen (HBsAg) in sera is an initial step for the diagnosis of hepatitis B virus (HBV) infection. The “a” determinant region (amino acid residues 124–147) is the main epitope for inducing a protective immune response. Mutations in the “a” determinant region, known as escape mutants, affect antigenicity and hinder attempts to detect HBV in serum [1]. HBsAg mutation is usually induced by immune escape of postexposure prophylaxis. In the 1970s, the introduction of the reversed passive hemagglutination (R-PHA) test revolutionized the detection of HBV [2]. Several enzyme immunoassays were then developed and showed increased sensitivity for the detection of HBV. However, it was still difficult to detect escape mutants using these methods [3]. Currently, chemiluminescent immunoassays (CLIA) and chemiluminescent enzyme immunoassays (CLEIA) are commonly used for HBV screening because they show higher sensitivities and specificities than the previous methods. In addition, CLIA and CLEIA allow us to quantify HBs-Ag, in terms of the HBs-Ag titer. The HBsAg titer in HB extracellular antigen (HBeAg)-positive chronic hepatitis B is positively correlated with serum HBV-DNA, intrahepatic double-stranded covalently closed circular DNA (cccDNA), and total HBV-DNA [4]. The HBsAg-HQ assay, the most recently introduced system, allows us to measure HBsAg at titers of > 0.005 IU/ml [5]. Advanced methods showing high sensitivity and low false-positive rates will become standard methods of measuring the HBsAg titer.