Abstract

Despite several studies regarding the correlation between serum HBsAg titers and viral loads, the association remains uncertain. Eighty‐nine individuals were selected randomly from a Chinese cohort of 2,258 subjects infected persistently with hepatitis B virus (HBV) for cross‐sectional and longitudinal analysis. Viral loads of mutant HBV are lower than those of wild type HBV. The serum HBsAg titers correlate positively with viral loads in both HBeAg positive and negative subjects (r = 0.449, P = 0.013; r = 0.300, P = 0.018, respectively). No correlation between serum HBsAg titer and viral loads was found in any of the four phases of chronic HBV infection. The serum HBsAg titers correlate positively with viral loads in the group with wild type sequences of the PreS/S, basal core promoter (BCP), and preC regions of HBV(r = 0.502, P = 0.040). However, the correlation was not seen in the group with mutations in these regions (r = 0.165, P = 0.257). The correlation between HBsAg titers and viral loads was seen in individuals with wild type PreS/S sequences but not in the subgroup with BCP double mutations or PreC stop mutation, although their sequences in the preS/S regions were wild type. All these findings were confirmed by the longitudinal analysis. In conclusion, the correlation between serum HBsAg levels and viral loads may not differ between HBeAg positive and negative individuals but may depend on wild‐type or mutated genomic sequences. Therefore, HBsAg quantitation may be used as a surrogate for viral loads in only wild‐type HBV infections. J. Med. Virol. 87:1351–1360, 2015. © 2015 The Authors. Journal of Medical Virology Published by Wiley Periodicals, Inc.

Highlights

  • Hepatitis B virus (HBV) has a circular, partially double-stranded DNA genome of about 3200 nucleotides with four open reading frames (ORFs), namely the precore/core, polymerase, surface, and X ORFs [Tiollais et al, 1985]

  • The P-value is close to significance. These findings suggest that the correlation between serum Hepatitis B surface antigen (HBsAg) levels and viral loads may not differ between HBeAg positive and negative individuals

  • The serum HBsAg titers were positively correlated with serum HBV DNA concentrations in the groups with wild type preS/S, PreC and basal core promoter (BCP) sequences (r 1⁄4 0.553, P 1⁄4 0.026; r 1⁄4 0.671, P 1⁄4 0.004, respectively) (Fig. 3B and C) but not in the groups with mutated sequences (r 1⁄4 0.148, P 1⁄4 320; r 1⁄4 0.220, P 1⁄4 0.125, respectively) (Fig. 3E and F). These findings suggest that the correlation between serum HBsAg levels and viral loads differs between individuals with wild type and mutated HBV sequences

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Summary

Introduction

Hepatitis B virus (HBV) has a circular, partially double-stranded DNA genome of about 3200 nucleotides with four open reading frames (ORFs), namely the precore/core, polymerase, surface, and X ORFs [Tiollais et al, 1985]. The HBsAg found in serum can include all three forms of the surface protein found in the mature HBV virion, the large (L), medium (M), and small (S) proteins. These proteins are encoded by the S-ORF which contains three, in-frame initiation codons and is divided into the Pre-S1, Pre-S2 and S domains [Locarnini and Bowden, 2012]. Detection of HBsAg in serum has been the hallmark of HBV infection and remains the cornerstone for the diagnosis of acute and chronic hepatitis B [Martinot-Peignoux et al, 2014]. Compared to HBV DNA, quantification of HBsAg is relatively inexpensive and has been used widely

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