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Clin Res Hepatol Gastroenterol. 2019 Oct 14. pii: S2210-7401(19)30189-5. doi: 10.1016/j.clinre.2019.08.005. [Epub ahead of print]

Characteristics of amino acid substitutions within the "a" determinant region of hepatitis B virus in chronically infected patients with coexisting HBsAg and anti-HBs.

Author information

1
Tianjin Second People's Hospital and Tianjin Institute of Hepatology, Tianjin, China; Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. Electronic address: houweicn@163.com.
2
Tianjin Second People's Hospital and Tianjin Institute of Hepatology, Tianjin, China.
3
Department of Biomedical Engineering, School of Medicine, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing, China.
4
Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA.
5
Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; Section of Gastroenterology, Ralph H Johnson Veterans Affairs Medical Center, Charleston, SC, USA; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain. Electronic address: synw@musc.edu.

Abstract

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.

KEYWORDS:

Amino acid substitution; Anti-HBs; Chronic hepatitis B; HBsAg; “a” determinant region

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