Journal of Istanbul Faculty of Medicine

SUBMITINFORMATION
EnglishTürkçe

Research Article


DOI :10.26650/IUITFD.2020.0093   IUP :10.26650/IUITFD.2020.0093    Full Text (PDF)

ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS

Bülent Çakal, Alp Atasoy, Bilger Çavuş, Aslı Çifcibaşı Örmeci, Mehveş Poda, Mesut Bulakçı, Mine Güllüoğlu, Mehmet Güven Günver, Filiz Akyüz

Objective: Occult hepatitis B infection (OBI) can be characterized by the long-term persistence of HBV DNA in the liver of individuals who test negative for the hepatitis B surface antigen (HBsAg) using the currently available assays. This study aimed to evaluate genotype, subgenotype and subtype profiles of HBVs obtained from patients with OBI. Material and Method: The study included 32 patients with OBI who were diagnosed with HBV DNA by Nested PCR method in liver biopsy samples of patients who underwent liver parenchymal biopsy due to HBsAg negative different clinic indications and 17 chronic hepatitis B patients. The MHR region of the HBV S gene was amplified using nested PCR. Sanger sequencing method was used to determine the genotype, subgenotypes and subtype/serotype of HBV. Results: In this study it was determined that the genotypes of all HBVs isolated from OBI and chronic hepatitis B patients were HBV/D, subgenotypes were respectively HBV/ D1 (75.5%), HBV/ D2 (6.1%) and HBV/D3 (18.4%), serotypes were respectively ayw2 (73.5%) and ayw3 (26.5%). Although the subgenotype of 28.1% of patients with OBI was determined as HBV/D3, none of the chronic hepatitis B patients had the HBV/D3 subgenotype. Conclusion: The potential effects of subgenotype HBV/D3 on the dynamics of viral biogenesis may be associated with OBI, characterized by low replication competence and HBsAg negativity.

Keywords: OBI, Genetic diversity, Genotypes, Subgenotypes, HBsAg Subtypes, Hepatitis B virus
DOI :10.26650/IUITFD.2020.0093   IUP :10.26650/IUITFD.2020.0093    Full Text (PDF)

OKÜLT HEPATİT B VİRÜSÜNÜN GENOTİP, SUBGENOTİP VE SUBTİP ANALİZİ

Bülent Çakal, Alp Atasoy, Bilger Çavuş, Aslı Çifcibaşı Örmeci, Mehveş Poda, Mesut Bulakçı, Mine Güllüoğlu, Mehmet Güven Günver, Filiz Akyüz

Amaç: Okült Hepatit B Virus (HBV) enfeksiyonu (Occult HBV infection; OBI) mevcut serolojik testler ile HBV yüzey antijeni (Surface antigen; HBsAg) negatif tespit edilen bireylerin karaciğerinde HBV genomunun uzun süreli persistan varlığı ile karakterizedir. Bu çalışmada OBI tanılı hastalardan elde edilen HBV’lerin genotip, subgenotip ve subtip profillerinin karakteristiğinin irdelenmesi amaçlanmıştır. Gereç ve Yöntem: Çalışmaya HBsAg negatif farklı klinik endikasyonlar nedeniyle karaciğer parankim biyopsisi gerçekleştirilen hastaların karaciğer biyopsi örneklerinde Nested PCR yöntemiyle HBV DNA varlığı tanımlanan 32 OBI tanılı hasta ile 17 kronik hepatit B hastası dahil edildi. HBV S gen MHR bölgesini hedefleyen DNA fragmanları nested PCR kullanılarak amplifiye edildi. HBV’nin genotip, subgenotip ve subtip/serotiplerinin belirlemek için Sanger sekans metodu kullanıldı. Bulgular: Bu çalışmada OBI ve kronik hepatit B hastalarından izole edilen HBV’lerin tümününün genotipi D, subgenotipler sırasıyla HBV/D1 (%75,5), HBV/D2 (%6,1) ve HBV/D3 (%18,4) serotipler sırasıyla ayw2 (%73,5) ve ayw3 (%26,5) olarak belirlenmiştir. OBI’li hastaların %28,1’nin subgenotipi HBV/D3 olarak belirlenmesine karşın kronik hepatit B hastalarının hiç birinde HBV/D3 subgenotipi saptanmamıştır. Sonuç: Subgenotip HBV/D3’ün viral biyogenezin dinamiği üzerindeki potansiyel etkileri HBsAg negatifliği ve düşük replikasyon yetkinliği ile karakterize OBI ile ilişkili olabilir. 

Keywords: OBI, Genetik varyasyon, Genotip, Subgenotip, HBsAg Subtipleri, Hepatit B virüsü

PDF View

References

  • 1. Revill PA, Chisari FV, Block JM, Dandri M, Gehring AJ, Guo H, et al. Lancet Gastroenterol. Hepatol 2019;4:545-58. google scholar
  • 2. Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F, Lok AS, and the Taormina Workshop on Occult HBV Infection Faculty Members. Update of the statements on biology and clinical impact of occult hepatitis B virus infection. J Hepatol 2019;71(2):397-408. [CrossRef] google scholar
  • 3. Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol 2008;49:652-7. [CrossRef] google scholar
  • 4. Torbenson M, Thomas DL. Occult hepatitis B. Lancet Infect Dis 2002;2:479-86. [CrossRef] google scholar
  • 5. Chemin I, Trepo C. Clinical impact of occult HBV infections. J Clin Virol 2005;34:15-21. [CrossRef] google scholar
  • 6. Ponde RAA. Molecular mechanisms underlying HBsAg negativity in occult HBV infection. Eur J Clin Microbiol Infect Dis 2015;34:1709-31. [CrossRef] google scholar
  • 7. Pollicino T, Raimondo G. Occult Hepatitis B Infection. Journal of Hepatology 2014;61:688-9. [CrossRef] google scholar
  • 8. Raimondo G, Caccamo G, Filomia R, Pollicino T. Occult HBV infection. Semin Immunopathol 2013;35:39-52. [CrossRef] google scholar
  • 9. Lugoboni F, Quaglio G, Civitelli P, Mezzelani P. Bloodborne viral hepatitis infections among drug users: the role of vaccination. Int J Environ Res Public Health 2009;6(1):400-13. [CrossRef] google scholar
  • 10. Chen BF, Chen PJ, Jow GM, Sablon E, Liu CJ, Chen DS, et al. High prevalence of mixed genotype infections in hepatitis B virus infected intravenous drug users. J Med Virol 2004;74(4):536-42. [CrossRef] google scholar
  • 11. Locarnini S, Zoulim F. Molecular genetics of HBV infection Antivir Ther 2010;3:3-14. [CrossRef] google scholar
  • 12. Seddigh-Tonekaboni S, Waters JA, Jeffers S, Gehrke R, Ofenloch B, Horsch A, et al. Effect of variation in the common “a” determinant on the antigenicity of hepatitis B surface antigen. J Med Virol 2000;60:113-21. [CrossRef] google scholar
  • 13. Waters J, Kennedy M, Voet P, Hauser P, Petre J, Carman W, et al. Loss of the common ‘a’ determinant of hepatitis B surface antigen by a vaccine-induced escape mutant. J Clin Invest 1992;90:2543-47. [CrossRef] google scholar
  • 14. Osiowy C. Detection of HBsAg mutants. J Med Virol 2006;78:48-51. [CrossRef] google scholar
  • 15. Huang CH, Yuan Q, Chen PJ, Zhang YL, Chen CR, Zheng QB, et al. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors. Journal of Hepatology 2012;57:720-9. [CrossRef] google scholar
  • 16. McMahon, BJ. The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B Hepatol Int 2009;3:334-42. [CrossRef] google scholar
  • 17. Purdy MA, Talekar G, Swenson P, Araujo A, Fields H. A New Algorithm for Deduction of Hepatitis B Surface Antigen Subtype Determinants from the Amino Acid Sequence. Intervirology 2007;50:45-51. [CrossRef] google scholar
  • 18. Norder H, Courouce AM, Coursaget P, Echevarria JM, Lee SD, Mushahwar IK, et al. Genetic diversity of hepatitis B virus strains derived worldwide: Genotypes, subgenotypes, and HBsAg subtypes. Intervirology 2004;47:289-309. [CrossRef] google scholar
  • 19. Kramvis A. Genotypes and Genetic Variability of Hepatitis B Virus. Intervirology 2014;57(3-4):141-50. [CrossRef] google scholar
  • 20. Zhang ZH, Wu CC, Chen XW, Li X, Li J, Lu MJ. Genetic variation of hepatitis B virus and its significance for pathogenesis. World J Gastroenterol 2016;22(1):126-44. [CrossRef] google scholar
  • 21. Revill PA, Tu T, Netter HJ, Yuen LKW, Locarnini SA, Littlejohn M. The evolution and clinical impact of hepatitis B virus genome diversity. Nature Reviews Gastroenterology & Hepatology 2020. [CrossRef] google scholar
  • 22. Blumberg BS, Alter HJ, Visnich S. A new antigen in leukemia sera. JAMA 1965;191:541. [CrossRef] google scholar
  • 23. Bancroft WH, Mundon FK, Russell PK. Detection of additional antigenic determinants of hepatitis B antigen. J Immunol 1972;109: 842-8. google scholar
  • 24. Weinberger KM, Bauer T, Bohm S, Jilg W. High genetic variability of the group-specific a-determinant of hepatitis B virus surface antigen (HBsAg) and the corresponding fragment of the viral polymerase in chronic virus carriers lacking detectable HBsAg in serum. J Gen Virol 2000;81:1165-74. [CrossRef] google scholar
  • 25. Raney AK, Johnson JL, Palmer CNA, McLachlan A. Members of the nuclear receptor superfamily regulate transcription from the hepatitis B virus nucleocapsid promoter. J Virol 1997;71:1058-71. [CrossRef] google scholar
  • 26. Pollicino T, Cacciola I, Saffioti F, Raimondo G. Hepatitis B virus PreS/S gene variants: Pathobiology and clinical implications. Journal of Hepatology 2014;61:408-17. [CrossRef] google scholar
  • 27. Sheldon J, Rode's B, Zoulim F, Bartholomeusz A, Soriano V Mutations affecting the replication capacity of the hepatitis B virus. Journal of Viral Hepatitis 2006;13:427-34. [CrossRef] google scholar
  • 28. Mirabelli C, Surdo M, Hemert F-V, Lian Z, Salpini R, Cento V. Specific mutations in the C-terminus domain of HBV surface antigen significantly correlate with low level of serum HBV-DNA in patients with chronic HBV infection. Journal of Infection 2015;70:288e298. [CrossRef] google scholar
  • 29. Huang X, Qin Y, Li W, Shi Q, Xue Y, Li J, et al. Molecular analysis of the hepatitis B virus presurface and surface gene in patients from eastern China with occult hepatitis B. J Med Virol 2013;85:979-86. [CrossRef] google scholar
  • 30. Chandra PK, Biswas A, Datta S, Banerjee A, Panigrahi R, Chakrabarti S. et al. Subgenotypes of hepatitis B virus genotype D (D1, D2, D3 and D5) in India: differential pattern of mutations, liver injury and occult HBV infection. J Viral Hepat 2009;16:749-56. [CrossRef] google scholar
  • 31. Datta S, Dasgupta D, Ghosh A, Ghosh S, Manna A, Datta S. Oncogenic potential of hepatitis B virus subgenotype D1 surpasses D3: significance in the development of hepatocellular carcinoma. Carcinogenesis 2018;39:283-92. [CrossRef] google scholar
  • 32. Khatun M, Mondal RK, Pal S, Baidya A, Bishnu D, Banerjee P, et al. Distinctiveness in virological features and pathogenic potentials of subgenotypes D1, D2, D3 and D5 of Hepatitis B virus. Sci Rep 2018;23;8(1):8055. [CrossRef] google scholar
  • 33. Alestig E, Söderström A, Norkrans G, Lindh M. Genetic Diversity of Genotype D3 in Acute Hepatitis B. J Med Virol 2013;85(7):1148-54. [CrossRef] google scholar
  • 34. Biswas A, Panigrahi R, Chandra PK, Banerjee A, Datta S, Pal M. Characterization of the Occult Hepatitis B Virus Variants Circulating among the Blood Donors from Eastern India. ScientificWorld Journal 2014;4:212704. google scholar
  • 35. Scheiblauer H, El-Nageh M, Diaz S, Nick S, Zeichhardt H, Grunert HP, et al. Performance evaluation of 70 hepatitis B virus (HBV) surface antigen (HBsAg) assays from around the world by a geographically diverse panel with an array of HBV genotypes and HBsAg subtypes Vox Sanguinis 2010;98:403-14. [CrossRef] google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Çakal, B., Atasoy, A., Çavuş, B., Çifcibaşı Örmeci, A., Poda, M., Bulakçı, M., Güllüoğlu, M., Günver, M.G., & Akyüz, F. (2021). ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS. Journal of Istanbul Faculty of Medicine, 84(3), 402-410. https://doi.org/10.26650/IUITFD.2020.0093


AMA

Çakal B, Atasoy A, Çavuş B, Çifcibaşı Örmeci A, Poda M, Bulakçı M, Güllüoğlu M, Günver M G, Akyüz F. ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS. Journal of Istanbul Faculty of Medicine. 2021;84(3):402-410. https://doi.org/10.26650/IUITFD.2020.0093


ABNT

Çakal, B.; Atasoy, A.; Çavuş, B.; Çifcibaşı Örmeci, A.; Poda, M.; Bulakçı, M.; Güllüoğlu, M.; Günver, M.G.; Akyüz, F. ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS. Journal of Istanbul Faculty of Medicine, [Publisher Location], v. 84, n. 3, p. 402-410, 2021.


Chicago: Author-Date Style

Çakal, Bülent, and Alp Atasoy and Bilger Çavuş and Aslı Çifcibaşı Örmeci and Mehveş Poda and Mesut Bulakçı and Mine Güllüoğlu and Mehmet Güven Günver and Filiz Akyüz. 2021. “ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS.” Journal of Istanbul Faculty of Medicine 84, no. 3: 402-410. https://doi.org/10.26650/IUITFD.2020.0093


Chicago: Humanities Style

Çakal, Bülent, and Alp Atasoy and Bilger Çavuş and Aslı Çifcibaşı Örmeci and Mehveş Poda and Mesut Bulakçı and Mine Güllüoğlu and Mehmet Güven Günver and Filiz Akyüz. “ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS.” Journal of Istanbul Faculty of Medicine 84, no. 3 (Nov. 2024): 402-410. https://doi.org/10.26650/IUITFD.2020.0093


Harvard: Australian Style

Çakal, B & Atasoy, A & Çavuş, B & Çifcibaşı Örmeci, A & Poda, M & Bulakçı, M & Güllüoğlu, M & Günver, MG & Akyüz, F 2021, 'ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS', Journal of Istanbul Faculty of Medicine, vol. 84, no. 3, pp. 402-410, viewed 23 Nov. 2024, https://doi.org/10.26650/IUITFD.2020.0093


Harvard: Author-Date Style

Çakal, B. and Atasoy, A. and Çavuş, B. and Çifcibaşı Örmeci, A. and Poda, M. and Bulakçı, M. and Güllüoğlu, M. and Günver, M.G. and Akyüz, F. (2021) ‘ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS’, Journal of Istanbul Faculty of Medicine, 84(3), pp. 402-410. https://doi.org/10.26650/IUITFD.2020.0093 (23 Nov. 2024).


MLA

Çakal, Bülent, and Alp Atasoy and Bilger Çavuş and Aslı Çifcibaşı Örmeci and Mehveş Poda and Mesut Bulakçı and Mine Güllüoğlu and Mehmet Güven Günver and Filiz Akyüz. “ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS.” Journal of Istanbul Faculty of Medicine, vol. 84, no. 3, 2021, pp. 402-410. [Database Container], https://doi.org/10.26650/IUITFD.2020.0093


Vancouver

Çakal B, Atasoy A, Çavuş B, Çifcibaşı Örmeci A, Poda M, Bulakçı M, Güllüoğlu M, Günver MG, Akyüz F. ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS. Journal of Istanbul Faculty of Medicine [Internet]. 23 Nov. 2024 [cited 23 Nov. 2024];84(3):402-410. Available from: https://doi.org/10.26650/IUITFD.2020.0093 doi: 10.26650/IUITFD.2020.0093


ISNAD

Çakal, Bülent - Atasoy, Alp - Çavuş, Bilger - Çifcibaşı Örmeci, Aslı - Poda, Mehveş - Bulakçı, Mesut - Güllüoğlu, Mine - Günver, MehmetGüven - Akyüz, Filiz. “ANALYSIS OF GENOTYPE, SUBGENOTYPE AND SEROTYPE OF OCCULT HEPATITIS B VIRUS”. Journal of Istanbul Faculty of Medicine 84/3 (Nov. 2024): 402-410. https://doi.org/10.26650/IUITFD.2020.0093



TIMELINE


Submitted04.08.2020
Accepted04.11.2020
Published Online12.07.2021

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE




Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.