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Review
. 2019 Nov 7:14:33.
doi: 10.1186/s13027-019-0253-6. eCollection 2019.

A meta-analysis on genetic variability of RT/HBsAg overlapping region of hepatitis B virus (HBV) isolates of Bangladesh

Md Golzar Hossain  1   2 , Keiji Ueda  1
Affiliations
Review

A meta-analysis on genetic variability of RT/HBsAg overlapping region of hepatitis B virus (HBV) isolates of Bangladesh

Md Golzar Hossain et al. Infect Agent Cancer. .

Abstract

Background and aim: Hepatitis B caused by HBV is a serious public health hazard prevalent worldwide including Bangladesh. Few scattered molecular studies of HBV have been reported in Bangladesh. This study aimed to analyze the genetic variability of RT/HBsAg overlapping region of HBV isolates of Bangladesh and determination of correlation among the genotype/serotype and HBsAg escape and/or drug-resistant mutations.

Methods: A total of 97 complete HBsAg sequences of Bangladeshi HBV isolates from 2005 to 2017 from NCBI GenBank were extracted and analyzed using several HBV bioinformatics tools such as Geno2pheno-HBV, HBV Serotyper, HIV-Grade:HBV-Tool, and CLC sequence viewer.

Results: The prevalence of genotypes A, C, and D are 18, 46 and 35% which correspond to serotype adw, adr, and ayw, respectively. The prevalence of HBsAg escape mutations is 51% and most of which (62%) are found in the genotype D followed by 32% in genotype C and 6% in genotype A. Interestingly most (24/36) of the sequences of HBsAg escape mutations contained 128 V mutant which all belongs to only serotype ayw3 (Genotype D). Prevalence of drug-resistant mutations is ~ 11%, most of which are from genotype C (63.64%) and D (36.36%). Lamivudine resistant mutations were found in ~ 11% of sequences followed by Telbivudine 10% and Adefovir 3% where Tenofovir showed susceptibility to all 97 sequences. Moreover, 7 among of 97 sequences showed both HBsAg and drugs resistant mutations and none of them are found due to the same nucleotide substitutions.

Conclusion: There is a strong correlation among the genotype/serotype and HBsAg escape and/or drug-resistant mutations. This meta-analytical review will be helpful for genotype-serotype prediction by PCR-based diagnosis and development of vaccine and/or diagnostic kits, and the treatment against HBV infection in the future.

Keywords: Bangladesh; Drug-resistant mutations; Genotype; HBsAg escape mutations; Hepatitis B virus (HBV); Serotype.

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Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Prevalence of HBV genotype and serotype. Ninety-seven complete small HBsAg coding sequences of Bangladeshi HBV isolates of year, 2005–2017 were collected from NCBI GenBank. The HBV genotype and serotype were re-determined by using the bioinformatics tool followed by an analysis of their overall prevalence of genotype (a) and serotype (b) circulating in Bangladesh. Chi-square test was performed to determine the statistical significance level and only the p-value greater than 0.05 was mentioned
Fig. 2
Fig. 2
Distribution of HBV genotype among the serotype. Relationship of HBV genotype and serotype of Bangladeshi HBV isolates from 2005 to 2017 was determined. Chi-square test was performed to determine the statistical significance level and only the p-value greater than 0.05 was mentioned
Fig. 3
Fig. 3
Prevalence of HBsAg escape and drug-resistant mutations in RT/HBsAg overlapping region. Mutations related to HBsAg escape and drug resistant of RT/HBsAg overlapping region were determined by using Geno2pheno-HBV and HIV Grade: HBV-Tool. a Overall prevalence of HBsAg escape (a) and drug-resistant mutations (b) circulating in Bangladesh from 2005 to 2017 determined by two different bioinformatics tools. c Specific mutations with their frequency related to HBsAg escape and drug-resistant in the RT/HBsAg overlapping region. The numbers within the bracket showed the frequency of that mutation
Fig. 4
Fig. 4
Distribution (Relationship) of HBsAg escape and drug-resistant mutations among the genotypes. Relationship of HBsAg escape and drug-resistant HBV mutations circulating in Bangladesh from 2005 to 2017 was determined (a and b). Chi-square test was performed to determine the statistical significance level and only the p-value greater than 0.05 was mentioned
Fig. 5
Fig. 5
Alignment of the nucleotide sequences (a) and amino acid sequences of HBsAg, (b) and Pol RT domain (c) of the sequences showed both HBsAg escape and drug-resistant mutations
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