Molecular and Serological Characterization of Hepatitis B Virus (HBV)-Positive Samples with Very Low or Undetectable Levels of HBV Surface Antigen

Kuhns, Mary C.; Holzmayer, Vera; Anderson, Mark; McNamara, Anne L.; Sauleda, Sílvia; Mbanya, Dora; Duong, Pham Tuan; Dung, Nguyen Tri; Cloherty, Gavin

doi:10.3390/v13102053

Cited by 19 publications

(16 citation statements)

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“…Furthermore, because the S gene’s open reading frame partially overlaps with that of the reverse transcriptase (RT) gene, mutations in the S gene cause antiviral resistance mutations to appear in the RT domain. The variation of S gene not only Strongly Affect HBsAg Detection ( Kuhns et al, 2021 ; Wang et al, 2021 ), but also leads to HBV drug resistance and immune escape ( Delfino et al, 2021 ). Drug resistance must be considered when a patient experiences a poor curative effect during a follow-up visit.…”

Section: Discussionmentioning

confidence: 99%

Reactivation of Occult Hepatitis B Virus Infection During Long-Term Entecavir Antiviral Therapy

et al. 2022

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Up to now, it has not been clear whether occult hepatitis B virus (HBV) infection (OBI) can be treated with antiviral therapy whether OBI can develop drug resistance gene mutation or not. We report a middle-aged female patient with OBI who showed HBV reactivation (HBVr) during more than 3 years of intermittent entecavir (ETV) antiviral therapy: seropositive HBV surface antigen (HBsAg), increased e antigen (HBeAg), and repeatedly elevated serum HBV DNA. Genotype analysis showed that the patient was infected with HBV type B. Genetic sequencing of HBV showed the mutants of S143T, D144G, and G145R in the S gene region, and the mutant of site 1896 in the pre-Core region coexisted with the wild type (G1896A/G). No mutation was found in other HBV gene segments. Drug resistance gene analysis found RtL229W mutant, resistant to lamivudine but sensitive to ETV and other nucleoside analogs. This case of OBI provides us with the following clinical experiences: Firstly, it is necessary to detect HBV genotype, mutation, and drug-resistant genes at the initial diagnosis, which can be helpful for reasonable treatment. Secondly, identifying the risk factors and mechanisms associated with HBVr could help quantify the risk of HBVr and manage the clinical consequences. Thirdly, the OBI patients with hepatitis B e antigen-positive, HBV DNA > 1 × 103 IU/ml should be recommended regular and continuous antiviral therapy as soon as possible to prevent the occurrence of hepatocirrhosis and hepatocellular carcinoma (HCC).

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Section: Discussionmentioning

confidence: 99%

Reactivation of Occult Hepatitis B Virus Infection During Long-Term Entecavir Antiviral Therapy

et al. 2022

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“…In the major hydrophilic region (MHR/aminoacids 99-169) of the S protein. G119R, Q129R, T140I, and D144A are the mutations of this region found in one study, affecting mainly the “a” determinant of MHR (aminoacids 124-147), which contains a cluster of B-cells epitopes[ 42 ]. P120T and S143L are other mutations associated with OBI[ 43 ].…”

Section: Mechanisms That Lead To Obimentioning

confidence: 99%

“…In the pre S1/S2 genomic region. The following pre-S1 mutations were found in one study: F25L, A28T, K57T, del 57-99, P65L, S78N, P89T, N98NK, N98NT, N98I, G102R; the following were found for pre S2: del 9-22, A11T, P36Q, and P54Q[ 42 ]. Mutations in this genomic region can affect antigenicity, immunogenicity, cell elimination, and/or expression of HBsAg, leading to the failure of its detection or reducing or even inhibiting the replication and/or secretion of virions and thus having a negative effect on HBsAg detection[ 46 ].…”

Section: Mechanisms That Lead To Obimentioning

confidence: 99%

“…With regard to antibodies, one study found that positive anti-HBs (≥ 10 mIU/mL) were more frequent in HBsAgNx [ARCHITECT HBsAg NEXT (sensitivity 0.005 IU/mL)]- negative than in HBsAgNx-positive nucleic acid testing yield samples ( P = 0.0014), while there was no significant difference for the HBsAgNx-negative vs HBsAgNx-positive OBI samples ( P = 0.0748)[ 42 ]. HBsAgNx is a “supersensitive” assay and its use in this study has been shown to improve HBsAg detection with 22.6% as compared to standard tests[ 42 ]. The masking of HBsAg by anti-HBs has been proposed as one reason for the lack of detection of OBI even if anti-HBs is undetectable[ 67 ].…”

Section: Mechanisms That Lead To Obimentioning

confidence: 99%

“…The masking of HBsAg by anti-HBs has been proposed as one reason for the lack of detection of OBI even if anti-HBs is undetectable[ 67 ]. Data from the first study[ 42 ] suggest that anti-HBs levels over 300 mIU/mL may affect the detection of samples with extremely low viral loads (median viral load: 4.42 IU/mL) and that the detection of such samples would require at least a 20000-fold excess of HBsAg to reach the detection limit of the HBsAgNx assay. Whether anti-HBs might be a consequence of vaccination in these cases or produced as a normal response to the immunogenic stimulus could be the subject of another discussion.…”

Section: Mechanisms That Lead To Obimentioning

confidence: 99%

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Occult hepatitis B — the result of the host immune response interaction with different genomic expressions of the virus

Gherlan¹

2022

WJCC

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With over 40 years of history, occult hepatitis B infection (OBI) continues to remain an important and challenging public health problem. Defined as the presence of replication-competent hepatitis B virus (HBV) DNA ( i.e. , episomal HBV covalently closed circular DNA) in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen (HBsAg) in currently available assays, OBI is currently diagnosed using polymerase chain reaction (PCR) and real-time PCR assays. However, all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI. In recent years, significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form. These factors are mainly related to the host immune system and, to a smaller proportion, to the virus. Both innate and adaptive immune responses are important in HBV infection management, and epigenetic changes driven by host mechanisms (acetylation, methylation, and microRNA implication) are added to such actions. Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection, the mechanisms of OBI are not mainly viral mutations.

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Occult hepatitis B in Iranian blood donors, an overview of the challenges: A narrative review

Ahmadi,

Sharifi,

Ghasemi

et al. 2023

Health Science Reports

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BackgroundOccult hepatitis B infection (OBI) is a transfusion‐transmitted infection. Although, screening the hepatitis B virus among blood donors can play an important role in increasing the health of blood products, OBI screening in blood transfusion centers is still a challenge. This review study aimed to appraise the challenges of OBI screening and its associated do's and don'ts in blood transfusion centers.MethodsIn this review study, a search was conducted on the electronic databases of PubMed, Web of Science, Scopus, Ovid, Irandoc, and Magiran from January 1996 to December 2020. Also, cross‐sectional studies that determined the prevalence of OBI or anti‐HBc were included in the study. In addition, studies with incomplete data on the prevalence of OBI were excluded.ResultsThe prevalence of OBI varies among Iranian blood donors. The rates reported by blood transfusion centers of Mashhad, Ahvaz, and Tehran were 0%, and Isfahan, Shiraz, and Kerman were 0.9%, 0.08%, and 2.36%, respectively. In areas with high prevalence of hepatitis B virus, OBI screening only by anti‐HBc test led to the exemption of blood donors from donating blood. Avoiding OBI screening also effected the risk of virus transmission to blood recipients. Plasma products had a higher risk (85%) of virus transmission.ConclusionsDetermining an appropriate screening strategy based on prevalence status, the cost‐effectiveness of screening tests, and the policies of each blood transfusion center is essential.

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Molecular and Serological Characterization of Hepatitis B Virus (HBV)-Positive Samples with Very Low or Undetectable Levels of HBV Surface Antigen

Cited by 19 publications

References 36 publications

Reactivation of Occult Hepatitis B Virus Infection During Long-Term Entecavir Antiviral Therapy

Reactivation of Occult Hepatitis B Virus Infection During Long-Term Entecavir Antiviral Therapy

Occult hepatitis B — the result of the host immune response interaction with different genomic expressions of the virus

Occult hepatitis B in Iranian blood donors, an overview of the challenges: A narrative review

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