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Simultaneous positivity for both hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs) is an atypical serological profile in chronic hepatitis B (CHB) patients. The exact mechanisms underlying the uncommon profile remains unclear. The aim of this study was to analyze the characteristics of amino acid substitutions within the "a" determinant region in a large cohort of CHB patients with coexistence of HBsAg and anti-HBs. In total 8687 CHB patients, of which 505 had coexisting HBsAg and anti-HBs, were enrolled in this study. Mutations within the "a" determinant region in 131 HBsAg+/anti-HBs+ patients and 150 age and gender matched HBsAg+/anti-HBs- patients were determined by direct sequencing and the characteristics of amino acid substitutions were analyzed. The prevalence of coexistence of HBsAg and anti-HBs in the CHB patients was 5.81%. Compared to the control subjects, there were more amino acid substitutions in HBsAg+/anti-HBs+ patients (30.5% vs. 12.7%, P<0.001), especially within the first loop of the "a" determinant region. The most frequent amino acid substitution was located at position s126 and the predominant substitution was sI126T in HBsAg+/anti-HBs+ patients with genotype C. The frequency of additional N-glycosylation sites in HBsAg+/anti-HBs+ patients and the control subjects was 3.8% and 0.6%, respectively. The accumulation and diversity of amino acid variations within "a" determinant region might contribute to the coexistence of HBsAg and anti-HBs. These findings extend understanding of the genetic mechanism of this atypical serological profile in CHB patients. Copyright © 2019 Elsevier Masson SAS. All rights reserved.


Wei Hou, Zhixiao Huo, Yanan Du, Cindy Wang, Wing-Kin Syn. Characteristics of amino acid substitutions within the "a" determinant region of hepatitis B virus in chronically infected patients with coexisting HBsAg and anti-HBs. Clinics and research in hepatology and gastroenterology. 2020 Nov;44(6):923-931

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PMID: 31624004

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