Patterns of hepatitis b virus immune escape and pol/rt mutations across clinical cohorts of patients with genotypes a, e and occult hepatitis b infection in Nigeria: A multi-centre study

Osasona, Oluwadamilola Gideon; Oluwagbenga, Oguntoye Oluwatosin; Arowosaye, Abiola O; Abdulkareem, Lukman O.; Adewumi, Moses Olubusuyi; Happi, Christian; Folarin, Onikepe A.

doi:10.1080/21505594.2023.2218076

Cited by 3 publications

(3 citation statements)

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“…The prevalence of HBV IEMs in the restricted, immunodominant "a"-determinant region (ADR) between amino acid positions 124-147 was 37.5% (n = 9/24), where nine connotes the number of samples with IEM mutations occurring in the antigenic determinant region. The prevalence of HBV IEMs in this study was slightly higher than what was earlier reported by Osasana in Nigeria and Lazarevec in Brazil, where a prevalence of 29% and 10.7% were reported, respectively [39,44]. This high prevalence may be due to the fact that the study participants were asymptomatic and, therefore, have yet to undergo HBV infection treatment.…”

Section: Discussioncontrasting

confidence: 79%

“…This is not surprising, as this is the most common virus genotype reported in the country [37]. Other genotypes reported in Nigeria are A, B, C, and D [36,38,39]. Specifically, we identified important substitutions in the "a"-determinant domain and clinically relevant mutations in the BCP and PC HBV genomic regions in asymptomatic hospital attendees.…”

Section: Discussionmentioning

confidence: 54%

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Detection of Immune Escape and Basal Core Promoter/Precore Gene Mutations in Hepatitis B Virus Isolated from Asymptomatic Hospital Attendees in Two Southwestern States in Nigeria

Sobajo,

Oguzie,

Adegboyega

et al. 2023

Viruses

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Several mutations in the surface (S), basal core promoter (BCP), and precore (PC) genes of the hepatitis B virus have been linked to inaccurate diagnosis and the development of immune escape mutants (IEMs) of the infection, which can lead to chronic infection. Understanding the prevalence and spread of these mutations is critical in the global effort to eliminate HBV. Blood samples were collected from 410 people in Osun and Ekiti states, southwest Nigeria, between 2019 and 2021. Participants were drawn from a group of asymptomatic people who were either blood donors, outpatients, or antenatal patients with no record of HBV infection at the medical outpatients’ unit of the hospital. DNA was extracted from plasma using a Qiagen DNEasy kit, followed by nested PCR targeting HBV S and BCP/PC genes. The Sanger sequencing method was used to sequence the positive PCR amplicons, which were further analyzed for IEMs, BCP, and PC mutations. HBV-DNA was detected in 12.4% (51/410) of individuals. After DNA amplification and purification, 47.1% (24) of the S gene and 76.5% (39) of the BCP/PC gene amplicons were successfully sequenced. Phylogenetic analysis showed that all the HBV sequences obtained in this study were classified as HBV genotype E. Mutational analysis of the major hydrophilic region (MHR) and a-determinant domain of S gene sequences revealed the presence of three immune escape mutations: two samples harbored a T116N substitution, six samples had heterogenous D144A/N/S/H substitution, and one sample had a G145E substitution, respectively. The BCP/PC region analysis revealed a preponderance of major BCP mutants, with the prevalence of BCP double substitutions ranging from 38.5% (A1762T) to 43.6% (G1764A). Previously reported classical PC mutant variants were observed in high proportion, including G1896A (33.3%) and G1899A (12.8%) mutations. This study confirms the strong presence of HBV genotype E in Nigeria, the ongoing circulation of HBV IEMs, and a high prevalence of BCP/PC mutants in the cohorts. This has implications for diagnosis and vaccine efficacy for efficient management and control of HBV in the country.

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Section: Discussioncontrasting

confidence: 79%

Section: Discussionmentioning

confidence: 54%

Detection of Immune Escape and Basal Core Promoter/Precore Gene Mutations in Hepatitis B Virus Isolated from Asymptomatic Hospital Attendees in Two Southwestern States in Nigeria

Sobajo,

Oguzie,

Adegboyega

et al. 2023

Viruses

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“…A194V has not been characterized but it has been reported in many studies while sS207N is linked to immune escape [ 38 , 39 , 40 ]. Other mutations identified which were associated with immune escape were sK122R, sT127P and sS140L which are found in the MHR [ 28 , 29 , 30 , 31 , 32 , 33 ]. Other mutations with clinical significance were sY100S, sK122R, sM197T, sW201*, sS204R and sS204N which impair the production and secretion of HBsAg, associated with low HBV viral load and OBI [ 25 , 26 , 27 , 28 , 29 , 34 , 35 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus Prevalence among HIV-Uninfected People Living in Rural and Peri-Urban Areas in Botswana

Anderson,

Mangogola,

Phinius

et al. 2024

Microorganisms

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(1) Background: we determined the prevalence of the hepatitis B virus (HBV) amongst people without human immunodeficiency virus (HIV) in rural and peri-urban areas in Botswana. (2) Methods: We screened for the hepatitis B surface antigen (HBsAg) from archived plasma samples of people without HIV (n = 2135) randomly selected from the Botswana Combination Prevention Program (BCPP) (2013–2018). We sequenced 415 bp of the surface region using BigDye sequencing chemistry. (3) Results: The median age of participants was 31 (IQR: 24–46) and 64% (1360/2135) were female. HBV prevalence was 4.0% (86/2135) [95% CI: 3.3–4.9]) and ranged between 0–9.2%. Older participants (>35 years) had increased odds of HBV positivity (OR: 1.94; 95% CI: [1.32–2.86]; p = 0.001). Thirteen samples were sequenced and seven (53.8%) were genotype A, three (23.1%) were genotype D and genotype E each. Clinically significant mutations were identified in the surface region, but no classic drug resistance mutations were identified. (4) Conclusions: We report an HBV prevalence of 4.0% (95% CI 3.3–4.9) among people without HIV in rural and peri-urban communities in Botswana with varying rates in different communities. A comprehensive national HBV program is required in Botswana to guide HBV prevention, testing and management.

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Incidence of Occult Hepatitis B Infection (OBI) and hepatitis B genotype characterization among blood donors in Cameroon

Mbencho,

Hafza,

Cao

et al. 2024

PLoS ONE

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Background Occult hepatitis B infection (OBI) is characterized by the presence of hepatitis B virus (HBV) DNA at low levels in serum (<200 IU/mL) with a negative hepatitis B surface antigen (HBsAg) test. OBI remains a major challenge to blood safety, particularly in HBV-endemic regions like Cameroon, where HBV detection relies solely on HBsAg testing. This cross-sectional study aimed to investigate the actual incidence and genotype characteristics of OBI in Cameroonian blood donors. Methods Between March and June 2023, samples were collected from 288 HBsAg-negative blood donors aged 18 to 55 years and analysed for antibodies against the HBV core (anti-HBc) and surface antigens (anti-HBs). Following DNA extraction from the serum samples, qualitative nested PCR and quantitative real-time PCR were used to detect HBV viral DNA and viral load respectively. For positive samples, sequencing of a fragment of the S gene was performed to identify the circulating HBV genotypes. Results The findings revealed that 58% (n = 167/288) of blood donors tested positive for anti-HBc, 29% (n = 83/288) tested positive for anti-HBs, and 26% (n = 75/288) being positive for both anti-HBc and anti-HBs. Occult hepatitis was confirmed in 4.5% of the blood donors, all of whom belonged to either HBV genotypes A or E, which are predominant in Cameroon. The amino acid substitution sA184V associated with HBsAg detection failure in genotype E was observed in 70% of OBI sequences, and the HBsAg immune escape variants (sT131N and sS143L) implicated in OBI were also observed. The mutation rtN139K in the reverse transcriptase (RT) domain of the overlapping HBV polymerase (P) gene was present in 17% of OBI-positive sequences of genotype E, likely contributing to masking HBsAg secretion. Conclusion The results suggest a considerable risk of transfusion-transmitted HBV in this region. Therefore, to ensure blood safety, nucleic acid testing (NAT) is recommended, as relying solely on HBsAg assays is insufficient to eliminate this risk.

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Patterns of hepatitis b virus immune escape and pol/rt mutations across clinical cohorts of patients with genotypes a, e and occult hepatitis b infection in Nigeria: A multi-centre study

Cited by 3 publications

References 77 publications

Detection of Immune Escape and Basal Core Promoter/Precore Gene Mutations in Hepatitis B Virus Isolated from Asymptomatic Hospital Attendees in Two Southwestern States in Nigeria

Detection of Immune Escape and Basal Core Promoter/Precore Gene Mutations in Hepatitis B Virus Isolated from Asymptomatic Hospital Attendees in Two Southwestern States in Nigeria

Hepatitis B Virus Prevalence among HIV-Uninfected People Living in Rural and Peri-Urban Areas in Botswana

Incidence of Occult Hepatitis B Infection (OBI) and hepatitis B genotype characterization among blood donors in Cameroon

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