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Characteristics of amino acid substitutions within the “a” determinant region of hepatitis B virus in chronically infected patients with coexisting HBsAg and anti-HBs - 22/11/20

Doi : 10.1016/j.clinre.2019.08.005 
Wei Hou a, b, , Zhixiao Huo a, Yanan Du c, Cindy Wang b, Wing-Kin Syn b, d, e,
a Tianjin Second People's Hospital and Tianjin Institute of Hepatology, Tianjin, China 
b Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA 
c Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing, China 
d Section of Gastroenterology, Ralph H Johnson Veterans Affairs Medical Center, Charleston, SC, USA 
e Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain 

Corresponding authors. Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Strom Thurmond Building, 30 Courtenay Drive, 29425 Charleston, SC, USA.Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South CarolinaStrom Thurmond Building, 30 Courtenay DriveCharlestonSC29425USA

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Highlights

There were more amino acid substitutions in HBsAg+/anti-HBs+ patients compared to the control subjects, especially within the first loop of the “a” determinant region in HBsAg+/anti-HBs+ patients.
The most frequent amino acid substitution was located at position s126 and the predominant substitution was sI126T.
sC137R was showed for the first time in HBsAg+/anti-HBs+ patients with genotype C.
The preferred amino acid substitutions with genotypic heterogeneity was revealed.

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Summary

Objectives

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.

Methods

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.

Results

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.

Conclusions

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.

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Keywords : Chronic hepatitis B, HBsAg, Anti-HBs, “a” determinant region, Amino acid substitution


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Vol 44 - N° 6

P. 923-931 - Novembre 2020 Ritorno al numero
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