1887

Journal of General Virology header logo

Volume 102, Issue 7

Endemic HBV among hospital in-patients in Bangladesh, including evidence of occult infection Open Access

Abstract

Bangladesh is one of the top-ten most heavily burdened countries for viral hepatitis, with hepatitis B (HBV) infections responsible for the majority of cases. Recombinant and occult HBV infections (OBI) have been reported previously in the region. We investigated an adult fever cohort (=201) recruited in Dhaka, to determine the prevalence of HBV and OBI. A target-enrichment deep sequencing pipeline was applied to samples with HBV DNA >3.0 log IU ml. HBV infection was present in 16/201 (8 %), among whom 3/16 (19 %) were defined as OBI (HBsAg-negative but detectable HBV DNA). Whole genome deep sequences (WGS) were obtained for four cases, identifying genotypes A, C and D. One OBI case had sufficient DNA for sequencing, revealing multiple polymorphisms in the surface gene that may contribute to the occult phenotype. We identified mutations associated with nucleos(t)ide analogue resistance in 3/4 samples sequenced, although the clinical significance in this cohort is unknown. The high prevalence of HBV in this setting illustrates the importance of opportunistic clinical screening and DNA testing of transfusion products to minimise OBI transmission. WGS can inform understanding of diverse disease phenotypes, supporting progress towards international targets for HBV elimination.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Bangladesh , epidemiology , hepatitis B virus , occult , screening and sequencing
Funding
This study was supported by the:
  • National Institute for Health Research
    • Principle Award Recipient: AnnaL McNaughton
  • Wellcome Trust (Award 00174A1A)
    • Principle Award Recipient: SusannaDunachie
  • Wellcome Trust (Award 110110Z/15/Z)
    • Principle Award Recipient: PhilippaC Matthews
  • Commonwealth (Award BDCS-2015-44)
    • Principle Award Recipient: FazleRabbi Chowdhury
© 2021 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001628
2021-07-30
2024-05-13
Loading full text...

Full text loading...

/deliver/fulltext/jgv/102/7/jgv001628.html?itemId=/content/journal/jgv/10.1099/jgv.0.001628&mimeType=html&fmt=ahah

References

  1. WHO Global hepatitis report, 2017 [Internet]. World Health Organization; [cited 2019 Apr 24]; 2017 http://www.who.int/hepatitis/publications/global-hepatitis-report2017/en
  2. WHO Global health sector strategy on viral hepatitis 2016-2021 [Internet]. World Health Organization; 2017 http://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en
  3. Munshi SU, Tran TTT, TNT V, Tabassum S, Sultana N et al. Molecular characterization of hepatitis B virus in Bangladesh reveals a highly recombinant population. PLoS One 2017; 12:e0188944 [View Article] [PubMed]
     [Google Scholar]
  4. Al Mahtab M. Elimination of hepatitis viruses: Bangladesh scenario. Euroasian J Hepatogastroenterol 2017; 7:40–42 [View Article] [PubMed]
     [Google Scholar]
  5. Uz-Zaman MH, Rahman A, Yasmin M. Epidemiology of hepatitis B virus infection in Bangladesh: Prevalence among general population, risk groups and genotype distribution. Genes (Basel) 2018; 9: [View Article]
     [Google Scholar]
  6. Cooke GS, Andrieux-Meyer I, Applegate TL, Atun R, Burry JR et al. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology commission. Lancet Gastroenterol Hepatol 2019; 4:135–184 [View Article] [PubMed]
     [Google Scholar]
  7. Childs L, Roesel S, Tohme RA. Status and progress of hepatitis B control through vaccination in the South-East Asia Region, 1992-2015. Vaccine 2018; 36:6–14 [View Article] [PubMed]
     [Google Scholar]
  8. Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F et al. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol 2019; 71:397–408 [View Article] [PubMed]
     [Google Scholar]
  9. Martin CM, Welge JA, Rouster SD, Shata MT, Sherman KE et al. Mutations associated with occult hepatitis B virus infection result in decreased surface antigen expression in vitro. J Viral Hepat 2012; 19:716–723 [View Article] [PubMed]
     [Google Scholar]
  10. Kim MH, Kang SY, Lee WI. Occult HBV among Anti-hbc alone: Mutation analysis of an HBV surface gene and pre-S gene. Yonsei Med J 2017; 58:557–563 [View Article] [PubMed]
     [Google Scholar]
  11. Malagnino V, Fofana DB, Lacombe K, Gozlan J. Occult Hepatitis B virus infection: An old entity with novel clinical involvements. Open Forum Infect Dis 2018; 5:ofy227 [View Article] [PubMed]
     [Google Scholar]
  12. Huo TI, Wu JC, Lee PC, Chau GY, Lui WY et al. Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis. Hepatology 1998; 28:231–236 [View Article]
     [Google Scholar]
  13. Colagrossi L, Hermans LE, Salpini R, Di Carlo D, Pas SD et al. Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe. BMC Infect Dis 2018; 18:251 [View Article]
     [Google Scholar]
  14. Coleman PF. Detecting hepatitis B surface antigen mutants. Emerg Infect Dis 2006; 12:198–203 [View Article] [PubMed]
     [Google Scholar]
  15. Mahtab MA, Akbar SMF, Rahman S. Hepatitis B surface antigen-negative, but HBV DNA-positive patients in Bangladesh. Bangladesh Med Res Counc Bull 2012; 38:104–107 [View Article] [PubMed]
     [Google Scholar]
  16. Jahan M, Islam MA, Akbar SMF, Takahashi K, Tabassum S et al. Anti-hbc screening of blood donors in Bangladesh: Relevance to containment of HBV propagation. J Clin Exp Hepatol 2016; 6:115–118 [View Article] [PubMed]
     [Google Scholar]
  17. L-P H, Liu DP, Chen QY, Harrison TJ, He X et al. Occult HBV infection may be transmitted through close contact and manifest as an overt infection. PLOS ONE 2015; 10:e0138552
     [Google Scholar]
  18. Candotti D, Lin CK, Belkhiri D, Sakuldamrongpanich T, Biswas S et al. Occult hepatitis B infection in blood donors from South East Asia: molecular characterisation and potential mechanisms of occurrence. Gut 2012; 61:1744–1753 [View Article] [PubMed]
     [Google Scholar]
  19. Center for Biologics Evaluation, Research Complete list of DSA for infectious agents and HIV diagnostic assays [Internet]. U.S. Food and Drug administration; 2019 https://www.fda.gov/vaccines-blood-biologics/complete-list-donor-screening-assays-infectious-agents-and-hiv-diagnostic-assays
  20. Allice T, Cerutti F, Pittaluga F, Varetto S, Gabella S et al. COBAS AmpliPrep-COBAS TaqMan hepatitis B virus (HBV) test: a novel automated real-time PCR assay for quantification of HBV DNA in plasma. J Clin Microbiol 2007; 45:828–834 [View Article] [PubMed]
     [Google Scholar]
  21. Thomson E, Ip CLC, Badhan A, Christiansen MT, Adamson W et al. Comparison of next-generation sequencing technologies for comprehensive assessment of full-length hepatitis C viral genomes. J Clin Microbiol 2016; 54:2470–2484 [View Article] [PubMed]
     [Google Scholar]
  22. Podlaha O, Gane E, Brunetto M, Fung S, Chuang WL et al. Large-scale viral genome analysis identifies novel clinical associations between Hepatitis B virus and chronically infected patients. Sci Rep 2019; 9:10529 [View Article] [PubMed]
     [Google Scholar]
  23. Martel N, Gomes SA, Chemin I, Trépo C, Kay A. Improved rolling circle amplification (RCA) of hepatitis B virus (HBV) relaxed-circular serum DNA (RC-DNA. J Virol Methods 2013; 193:653–659 [View Article] [PubMed]
     [Google Scholar]
  24. Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J 2011; 17:10–12 [View Article]
     [Google Scholar]
  25. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods 2012; 9:357–359 [View Article] [PubMed]
     [Google Scholar]
  26. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25:1754–1760 [View Article] [PubMed]
     [Google Scholar]
  27. Simmonds P. SSE: a nucleotide and amino acid sequence analysis platform. BMC Res Notes 2012; 5:50 [View Article] [PubMed]
     [Google Scholar]
  28. Kumar S, Stecher G, Tamura K. MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets. Mol Biol Evol 2016; 33:1870–1874 [View Article] [PubMed]
     [Google Scholar]
  29. FigTree [Internet]. [cited 2020 Jan 23]. Available from; 2020 http://tree.bio.ed.ac.uk/software/figtree
  30. McNaughton AL, Revill PA, Littlejohn M, Matthews PC, Ansari MA. Analysis of genomic-length HBV sequences to determine genotype and subgenotype reference sequences. J Gen Virol 2020; 101:271–283 [View Article]
     [Google Scholar]
  31. Martin DP, Murrell B, Golden M, Khoosal A, Muhire B. RDP4: Detection and analysis of recombination patterns in virus genomes. Virus Evol 2015; 1:vev003 [View Article] [PubMed]
     [Google Scholar]
  32. Beloukas A, Geretti AM. Hepatitis B Virus Drug Resistance. Antimicrobial Drug Resistance 20171227–1242
     [Google Scholar]
  33. Mokaya J, McNaughton AL, Bester PA, Goedhals D, Barnes E et al. Hepatitis B virus resistance to tenofovir: fact or fiction? A synthesis of the evidence to date. Wellcome Open Res 2020; 5:151 [View Article]
     [Google Scholar]
  34. Raheel M, Choga WT, Blackard JT. The distribution of hepatitis B virus surface antigen polymorphisms at positions associated with vaccine escape. J Med Virol 2020 [View Article] [PubMed]
     [Google Scholar]
  35. Hossain MG, Ueda K. A meta-analysis on genetic variability of RT/HBsAg overlapping region of hepatitis B virus (HBV) isolates of Bangladesh. Infect Agent Cancer 2019; 14:33 [View Article] [PubMed]
     [Google Scholar]
  36. Shaha M, Hadisur Rahman M, Jahan M, Dey SK, Das KC et al. Identification of a novel tri-genotypic recombinant Hepatitis B virus in Bangladesh. Virus Res 2018; 255:154–156 [View Article] [PubMed]
     [Google Scholar]
  37. Manesis EK. HBeAg-negative chronic hepatitis B: from obscurity to prominence. J Hepatol 2006; 45:343–346 [View Article] [PubMed]
     [Google Scholar]
  38. Kim H, Lee SA, Kim DW, Lee SH, Kim BJ. Naturally occurring mutations in large surface genes related to occult infection of hepatitis B virus genotype c. PLOS ONE 2013; 8:e54486
     [Google Scholar]
  39. Mokaya J, McNaughton AL, Hadley MJ, Beloukas A, Geretti AM et al. A systematic review of hepatitis B virus (HBV) drug and vaccine escape mutations in Africa: A call for urgent action. PLoS Negl Trop Dis 2018; 12:e0006629 [View Article] [PubMed]
     [Google Scholar]
  40. Lee SA, Kim H, Kim H, Kim BJ. Nucleotide change of codon 182 in the surface gene of hepatitis B virus genotype C leading to truncated surface protein is associated with progression of liver diseases. J Hepatol 2012; 56:63–69 [View Article] [PubMed]
     [Google Scholar]
  41. Mokaya J, Maponga TG, McNaughton AL, Van Schalkwyk M, Hugo S et al. Evidence of tenofovir resistance in chronic hepatitis B virus (HBV) infection: An observational case series of South African adults. J Clin Virol 2020; 129:104548 [View Article] [PubMed]
     [Google Scholar]
  42. Rahman MA, Hakim F, Ahmed M, Ahsan CR, Nessa J et al. Prevalence of genotypes and subtypes of hepatitis B viruses in Bangladeshi population. Springerplus 2016; 5:278 [View Article] [PubMed]
     [Google Scholar]
  43. Wang ML, Wu D-B, Tao YC, Chen LL, Liu CP et al. The truncated mutant HBsAg expression increases the tumorigenesis of hepatitis B virus by regulating TGF-β/Smad signaling pathway. Virol J 2018; 15:61 [View Article] [PubMed]
     [Google Scholar]
  44. McNaughton AL, Roberts HE, Bonsall D, de Cesare M, Mokaya J et al. Illumina and Nanopore methods for whole genome sequencing of hepatitis B virus (HBV. Sci Rep 2019; 9:7081 [View Article] [PubMed]
     [Google Scholar]
  45. Yan B, Lv J, Feng Y, Liu J, Ji F et al. Temporal trend of hepatitis B surface mutations in the post-immunization period: 9 years of surveillance (2005-2013) in eastern China. Sci Rep 2017; 7:6669 [View Article] [PubMed]
     [Google Scholar]
  46. Mamun-Al M. Past, present, and future of viral hepatitis in Bangladesh. Euroasian J Hepatogastroenterol 2016; 6:43–44 [View Article] [PubMed]
     [Google Scholar]
  47. Astbury S, Da Costa Nunes Soares MM, Peprah E, King BJ, Jardim ACG et al. Extraction-free direct PCR from dried serum spots permits HBV genotyping and RAS identification by Sanger and minION sequencing. biorxiv 2019
     [Google Scholar]
  48. McNaughton AL, D’Arienzo V, Ansari MA, Lumley SF, Littlejohn M et al. Insights from deep sequencing of the HBV genome–unique, tiny, and misunderstood. Gastroenterology 2019; 156:384–399 [View Article] [PubMed]
     [Google Scholar]
  49. Downs LO, Matthews P, Vawda S, Bester A, Lythgoe K et al. Bimodal distribution and set point HBV DNA viral loads in chronic infection: retrospective analysis of cohorts from the UK and South Africa. Wellcome Open Res 2020; 5:113 [View Article]
     [Google Scholar]
  50. Tamandjou CR, Maponga TG, Chotun N, Preiser W, Andersson MI. Is hepatitis B birth dose vaccine needed in Africa. Pan Afr Med J 2017; 27:18 [View Article] [PubMed]
     [Google Scholar]
  51. Kim H, Kim B-J. Association of preS/S mutations with cccult Hepatitis B Virus (HBV) infection in South Korea: transmission potential of distinct cccult HBV variants. Int J Mol Sci 2015; 16:13595–13609 [View Article] [PubMed]
     [Google Scholar]
  52. Wang J, Zhang P, Zeng J, Du P, Zheng X et al. Occurrence of occult hepatitis B virus infection associated with envelope protein mutations according to anti-HBs carriage in blood donors. IntJ Infect Dis 2020; 92:38–45 [View Article]
     [Google Scholar]
  53. Pollicino T, Raffa G, Costantino L, Lisa A, Campello C et al. Molecular and functional analysis of occult hepatitis B virus isolates from patients with hepatocellular carcinoma. Hepatology 2007; 45:277–285 [View Article] [PubMed]
     [Google Scholar]
  54. Javanmard D, Namaei MH, Farahmand M, Ziaee A, Amini E et al. Molecular and serological characterization of occult hepatitis B virus infection among patients with hemophilia. J Med Virol 2019; 91:1519–1527 [View Article] [PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001628
Loading
Endemic HBV among hospital in-patients in Bangladesh, including evidence of occult infection
J. Gen. Virol. 102, 001628 (2021); https://doi.org/10.1099/jgv.0.001628
/content/journal/jgv/10.1099/jgv.0.001628
/content/journal/jgv/10.1099/jgv.0.001628
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error