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

Hou, Wei; Huo, Zhixiao; Du, Yanan; Wang, Cindy; Syn, Wing Kin

doi:10.1016/j.clinre.2019.08.005

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…The current mainstream hypotheses included mutations in the viral genome and hosts immune status [ 12 , 15 ]. Previously reported rates of coexistence of HBsAg and HBsAb vary widely, ranging from 0.3% to over 30% [ 10 , 11 , 15 , 18 , 21 , 22 ]. The coexistence of HBsAg and HBsAb (23.39%, 87/372) in our study was comparable with the incidence (20.67%, 234/1132) reported by Wang et al [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Characteristics and clinical treatment outcomes of chronic hepatitis B children with coexistence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg

Gu,

Li,

Yao

et al. 2024

BMC Med

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Background The coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) represents an uncommon serological pattern observed in patients with hepatitis B virus (HBV) infection, and its underlying mechanism and clinical significance have not been well established. The aim of this study was to investigate the association between this serological profile and clinical treatment outcomes in children with chronic hepatitis B (CHB). Methods This retrospective cohort study included 372 treatment-naïve CHB children from the Hunan Children’s Hospital. The participants were categorized into HBsAb-positive group and HBsAb-negative group. The associations between HBsAb positive status to clinical outcomes were assessed using Cox proportional hazard regression. Receiver operating characteristic curve was conducted to evaluate the prediction ability in HBsAg loss. Results The coexistence of HBsAg and HBsAb accounted for 23.39% (87/372) of the participants. The crude incidence rates of HBsAg loss, hepatitis B e antigen (HBeAg) clearance, and HBV-DNA undetectability were higher in the HBsAb-positive group compared with the HBsAb-negative group (37.46 vs. 17.37, 49.51 vs. 28.66, 92.11 vs. 66.54 per 100 person-years, respectively, all P < 0.05). The Cox regression analysis revealed a significant association between this serological profile and an increased likelihood of HBsAg loss (HR = 1.78, P = 0.001), and HBeAg clearance (HR = 1.78, P = 0.001). In addition, a combination of HBsAb ≥ 0.84 log10 IU/L and age ≤ 5 years can help identify patients likely to achieve HBsAg loss after antiviral therapy, with an AUC of 0.71. Conclusions Children who are positive for both HBsAg and HBsAb demonstrate a higher probability of favorable outcomes after antiviral treatment. Thus, children with HBsAb-positive CHB should be actively treated to achieve functional cure.

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Section: Discussionmentioning

confidence: 99%

Characteristics and clinical treatment outcomes of chronic hepatitis B children with coexistence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg

Gu,

Li,

Yao

et al. 2024

BMC Med

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“…Theoretically, the simultaneous presence of both positive hepatitis B surface antigen (HBsAg) and HBsAb in circulation should not appear in the same patient. However, this understanding has been challenged by several studies indicating the HBsAg+/HBsAb+ in chronic HBV patients from 2.63% to 8.9% (7)(8)(9)(10)(11). The mechanism underlying the simultaneous presence of HBsAg and HBsAb remains unclear and even controversial.…”

Section: Introductionmentioning

confidence: 99%

“…The antigenicity alteration of HBsAg could influence the recognition and neutralization (NT) between HBsAg and HBsAb (15,16). Several previous studies have attributed the HBsAg+/HBsAb+ serological patterns to aa substitutions that occurred in the "a" determinant of HBsAg resulting in immune evasion (10,17). The mutation of the HBV genome acquired during the disease process led to HBsAb being incapable of binding mutated HBsAg (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing

et al. 2021

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BackgroundThis study aimed to explore the molecular mechanism of the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) serological pattern via intensive characterization of HBV s gene in both chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients.MethodA total of 73 HBsAg+/HBsAb+ patients (CHB = 36, HCC = 37) and 96 HBsAg+/HBsAb− patients (CHB = 47, HCC = 49) were enrolled from 13 medical centers in China. The sequence features were elaborated based on the combination of next-generation sequencing (NGS) and multidimensional bioinformatics analysis.ResultsThe 16 high-frequency missense mutations, changes of stop codon mutation, clustering, and random forest models based on quasispecies features demonstrated the significant discrepancy power between HBsAg+/HBsAb+ and HBsAg+/HBsAb− in CHB and HCC, respectively. The immunogenicity for cytotoxic T lymphocyte (CTL) epitope Se and antigenicity for the major hydrophilic region (MHR) were both reduced in HBsAg+/HBsAb+ patients (CTL Se: p < 0.0001; MHR: p = 0.0216). Different mutation patterns were observed between HBsAg+/HBsAb+ patients with CHB and with HCC. Especially, mutations in antigenic epitopes, such as I126S in CHB and I126T in HCC, could impact the conformational structure and alter the antigenicity/immunogenicity of HBsAg.ConclusionBased on NGS and bioinformatics analysis, this study indicates for the first time that point mutations and quasispecies diversities of HBV s gene could alter the MHR antigenicity and CTL Se immunogenicity and could contribute to the concurrent HBsAg+/HBsAb+ with different features in HCC and CHB. Our findings might renew the understanding of this special serological profile and benefit the clinical management in HBV-related diseases.

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Controversies in Treating Chronic Hepatitis B Virus Infection

Sarowar

Hirode

Janssen

et al. 2021

Clinics in Liver Disease

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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

Cited by 5 publications

References 29 publications

Characteristics and clinical treatment outcomes of chronic hepatitis B children with coexistence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg

Characteristics and clinical treatment outcomes of chronic hepatitis B children with coexistence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg

The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing

Controversies in Treating Chronic Hepatitis B Virus Infection

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