The mechanism of the coexistence of HBsAg and anti-HBs is still unclear. This study investigated the variations located in the major hydrophilic region (MHR) of HBV from individuals with simultaneous HBsAg and anti-HBs in Guangzhou, southern China. Among 4455 samples analyzed, 179 (4.02%) patients were discovered with both HBsAg and anti-HBs. Finally, 44 individuals with concurrent HBsAg and anti-HBs (defined as group I), and 88 patients with positive HBsAg and negative anti-HBs (defined as group II, served as control) were enrolled in the study. The number of residue changes per 100 residues within the MHR in group I was 7.1 times more frequent than group II (P < 0.001) and was discovered mostly in the MHR1 (aa99-119) (P < 0.001). Two or more residue changes in the MHR were discovered in 15 patients (34.1%) of group I, but were found in only one (1.1%) patient of group II (P < 0.001). The most common variants in group I were at positions s101Q, s133M, s126T/I, s131T, s145G, s120P, and s129Q. In addition, sQ101 K, sT131N, and sM133L were more frequently discovered in group I with significant difference (P < 0.05). In chronic hepatitis B (CHB) patients, the simultaneous of HBsAg and anti-HBs were accompanied with an increase of MHR variants, and suggested that the HBsAg mutants were selected by naturally acquired anti-HBs during chronic carriage.
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