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Hepatitis B, C and D virus genotypes detected in HBsAg- or anti-HCV-positive people from the Republic of Moldova

Abstract

In the Republic of Moldova, little is known about hepatitis B, C and D virus (HBV, HCV, HDV) genotypes, although the genetic variant may influence the course and outcome of disease. For HBV genotyping, 301 hepatitis B surface antigen (HBsAg)-positive sera collected in 2010 and 2011 from drug users, prison inmates, commercial sex workers, and the general population in different geographical regions were investigated. The 31 HBsAg-positive sera collected in 2011 were also tested for HDV. Eighty-eight anti-HCV-positive sera collected between 2010 and 2011 from the general population and health care workers were used for HCV genotyping. Phylogenetic analysis of 84 HBV sequences showed that most of the viruses belonged to genotype D (n = 82, 97.6%), predominantly to the subgenotype D1/D2 cluster (n = 75/82, 91.5%). One sequence (74110) clustered as an outlier to this cluster, and six sequences belonged to subgenotype D3. Only two subgenotype A2 sequences were found. Cloning of six samples with ambiguous sequence chromatogram signals showed no mixed infections. Phylogenetic analysis of HCV sequences from 66 patients showed a predominance of subtype 1b (n = 63, 95.5%). Two sequences belonged to subtype 3a, and one to subtype 2a. HDV RNA belonging to genotype 1 was found in two sera (2/31, 6.5%). Thus, genotypes prevalent in Europe were detected for all three hepatitis viruses. For both HBV and HCV, one genotype was dominant, while occasional other variants seem to be restricted to certain cohorts and/or transmission routes.

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References

  1. WHO (2015) World Hepatitis Day, 28 July 2014. https://www.who.int/campaigns/hepatitis-day/2014/event/en/

  2. WHO (2015) Hepatitis B, Fact sheet N°204. Updated July 2015 https://www.who.int/mediacentre/factsheets/fs204/en/

  3. Alfaiate D, Deny P, Durantel D (2015) Hepatitis delta virus: from biological and medical aspects to current and investigational therapeutic options. Antivir Res 122:112–129. https://doi.org/10.1016/j.antiviral.2015.08.009

    CAS  Article  PubMed  Google Scholar 

  4. WHO (2015) Hepatitis C, Fact sheet N°164. Updated July 2015. https://www.who.int/mediacentre/factsheets/fs164/en/

  5. Croagh CM, Desmond PV, Bell SJ (2015) Genotypes and viral variants in chronic hepatitis B: A review of epidemiology and clinical relevance. World J Hepatol 7(3):289–303. https://doi.org/10.4254/wjh.v7.i3.289

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lin CL, Kao JH (2015) Hepatitis B virus genotypes and variants. Cold Spring Harb Perspect Med 5(5):a021436. https://doi.org/10.1101/cshperspect.a021436

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mayerat C, Mantegani A, Frei PC (1999) Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection? J Viral Hepat 6(4):299–304

    CAS  Article  PubMed  Google Scholar 

  8. Preciado MV, Valva P, Escobar-Gutierrez A, Rahal P, Ruiz-Tovar K, Yamasaki L, Vazquez-Chacon C, Martinez-Guarneros A, Carpio-Pedroza JC, Fonseca-Coronado S, Cruz-Rivera M (2014) Hepatitis C virus molecular evolution: transmission, disease progression and antiviral therapy. World J Gastroenterol 20(43):15992–16013. https://doi.org/10.3748/wjg.v20.i43.15992

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Sunbul M (2014) Hepatitis B virus genotypes: global distribution and clinical importance. World J Gastroenterol 20(18):5427–5434. https://doi.org/10.3748/wjg.v20.i18.5427

    Article  PubMed  PubMed Central  Google Scholar 

  10. Alvarado-Mora MV, Locarnini S, Rizzetto M, Pinho JR (2013) An update on HDV: virology, pathogenesis and treatment. Antivir Ther 18(3 Pt B):541–548. https://doi.org/10.3851/IMP2598

    Article  PubMed  Google Scholar 

  11. WHO (2015) Hepatitis B (HepB3) immunization coverage among 1-year-old (%). https://apps.who.int/gho/data/node.main.A828?lang=en

  12. Guriev V, Spanu C, Isac M, Sajen O, Spinu I, Casaidi E (2013) Evolution of epidemical process of acute viral hepatitis B, C and D in the context of realization of National Programs for viral hepatitis B, C and D prevention. Romanian. National Center of Public Health, Chisinau, Republic of Moldova, Curierul Medical 56(5):172–176

  13. National Center of Public Health (2012) National Program for Control of Hepatitis B, C and D for the years 2012–2016. Romanian Official publication Nr 34-37, article Nr 115:1–20

  14. National Center of Public Health (2013) Epidemiological surveillance of viral hepatitis Romanian. Epidemiological state surveillance of public health in the Republic of Moldova. Natl Rep 2013:95–102

    Google Scholar 

  15. Hubschen JM, Mbah PO, Forbi JC, Otegbayo JA, Olinger CM, Charpentier E, Muller CP (2011) Detection of a new subgenotype of hepatitis B virus genotype A in Cameroon but not in neighbouring Nigeria. Clin Microbiol Infect 17(1):88–94. https://doi.org/10.1111/j.1469-0691.2010.03205.x

    CAS  Article  PubMed  Google Scholar 

  16. Olinger CM, Venard V, Njayou M, Oyefolu AO, Maiga I, Kemp AJ, Omilabu SA, le Faou A, Muller CP (2006) Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E and A in West Africa: new subtypes, mixed infections and recombinations. J Gen Virol 87(Pt 5):1163–1173. https://doi.org/10.1099/vir.0.81614-0

    CAS  Article  PubMed  Google Scholar 

  17. Hubschen JM, Jutavijittum P, Thammavong T, Samountry B, Yousukh A, Toriyama K, Sausy A, Muller CP (2011) High genetic diversity including potential new subtypes of hepatitis C virus genotype 6 in Lao People’s Democratic Republic. Clin Microbiol Infect 17(12):E30–E34. https://doi.org/10.1111/j.1469-0691.2011.03665.x

    CAS  Article  PubMed  Google Scholar 

  18. Andernach IE, Leiss LV, Tarnagda ZS, Tahita MC, Otegbayo JA, Forbi JC, Omilabu S, Gouandjika-Vasilache I, Komas NP, Mbah OP, Muller CP (2014) Characterization of hepatitis delta virus in sub-Saharan Africa. J Clin Microbiol 52(5):1629–1636. https://doi.org/10.1128/JCM.02297-13

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Gish RG, Yi DH, Kane S, Clark M, Mangahas M, Baqai S, Winters MA, Proudfoot J, Glenn JS (2013) Coinfection with hepatitis B and D: epidemiology, prevalence and disease in patients in Northern California. J Gastroenterol Hepatol 28(9):1521–1525. https://doi.org/10.1111/jgh.12217

    Article  PubMed  Google Scholar 

  20. Ho E, Deltenre P, Nkuize M, Delwaide J, Colle I, Michielsen P, Belgian Association for the Study of the L (2013) Coinfection of hepatitis B and hepatitis delta virus in Belgium: a multicenter BASL study. Prospective epidemiology and comparison with HBV mono-infection. J Med Virol 85(9):1513–1517. https://doi.org/10.1002/jmv.23653

    CAS  Article  PubMed  Google Scholar 

  21. Niederau C, Amani A, Thiel A (2015) Long-term follow-up of HBsAg-positive patients in Germany. Eur J Gastroenterol Hepatol. https://doi.org/10.1097/MEG.0000000000000487

    Google Scholar 

  22. Yu X, Guo R, Ke S, Huang Q, Lin C, Lin Z, Chen S, Li J, Yang P, Su Z (2015) Changes in HBsAg titer and HBV DNA load and their correlation in patients with chronic hepatitis B and HBV-related liver cirrhosis Chinese. Nan fang yi ke da xue xue bao. J South Med Univ 35(5):682–686

    Google Scholar 

  23. Constantinescu I, Nedelcu F, Toader MA, Daniela V (2008) Clinical and therapeutical importance of HBV genotyping in Romania. J Med Life 1(2):165–173

    PubMed  PubMed Central  Google Scholar 

  24. Malyy VP, Lyadova TI, Boyko VV, Gololobova OV, Karazina VN (2011) Clinical significance of genotyping obligate hepatotropic viruses Russian. Clin Immunol Allergol Infectiol 6–7:48–53

    Google Scholar 

  25. Yousif M, Kramvis A (2013) Genotype D of hepatitis B virus and its subgenotypes: an update. Hepatol Res 43(4):355–364. https://doi.org/10.1111/j.1872-034X.2012.01090.x

    CAS  Article  PubMed  Google Scholar 

  26. Sultana C, Oprisan G, Szmal C, Vagu C, Temereanca A, Dinu S, Teleman MD, Ruta S (2011) Molecular epidemiology of hepatitis C virus strains from Romania. J Gastrointest Liver Dis 20(3):261–266

    Google Scholar 

  27. Esteban JI, Sauleda S, Quer J (2008) The changing epidemiology of hepatitis C virus infection in Europe. J Hepatol 48(1):148–162. https://doi.org/10.1016/j.jhep.2007.07.033

    Article  PubMed  Google Scholar 

  28. Ripoli M, Pazienza V (2011) Impact of HCV genetic differences on pathobiology of disease. Expert Rev Anti-Infect Ther 9(9):747–759. https://doi.org/10.1586/eri.11.94

    CAS  Article  PubMed  Google Scholar 

  29. Pascarella S, Negro F (2011) Hepatitis D virus: an update. Liver Int 31(1):7–21. https://doi.org/10.1111/j.1478-3231.2010.02320.x

    CAS  Article  PubMed  Google Scholar 

  30. Le Gal F, Badur S, Hawajri NA, Akyuz F, Kaymakoglu S, Brichler S, Zoulim F, Gordien E, Gault E, Deny P (2012) Current hepatitis delta virus type 1 (HDV1) infections in central and eastern Turkey indicate a wide genetic diversity that is probably linked to different HDV1 origins. Arch Virol 157(4):647–659. https://doi.org/10.1007/s00705-011-1212-8

    CAS  Article  PubMed  Google Scholar 

  31. Popescu GA, Otelea D, Gavriliu LC, Neaga E, Popescu C, Paraschiv S, Fratila M (2013) Epidemiology of hepatitis D in patients infected with hepatitis B virus in bucharest: a cross-sectional study. J Med Virol 85(5):769–774. https://doi.org/10.1002/jmv.23524

    CAS  Article  PubMed  Google Scholar 

  32. Olinger CM, Lazouskaya NV, Eremin VF, Muller CP (2008) Multiple genotypes and subtypes of hepatitis B and C viruses in Belarus: similarities with Russia and Western European influences. Clin Microbiol Infect 14:575–581

    CAS  Article  PubMed  Google Scholar 

  33. Sandres-Saune K, Deny P, Pasquier C, Thibaut V, Duverlie G, Izopet J (2003) Determining hepatitis C genotype by analyzing the sequence of the NS5B region. J Virol Methods 109:187–193

    CAS  Article  PubMed  Google Scholar 

  34. Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24(8):1596–1599. https://doi.org/10.1093/molbev/msm092

    CAS  Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank the Ministry of Foreign and European Affairs in Luxembourg for financial support. The authors also thank Laura Țurcan and Irina Malanco, National Centre of Public Health, Chisinau, Republic of Moldova, for their contributions to the investigation of the specimens for the present study.

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Correspondence to Judith M. Hübschen.

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Oral informed consent was obtained from all participants to the screening program. A formal National Ethics Committee was set up only in 2013 when the investigations for the present study were already concluded.

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The authors declare that they have no conflict of interest.

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Handling Editor: Michael A. Purdy.

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Gori, A., Gheorgita, S., Spinu, C. et al. Hepatitis B, C and D virus genotypes detected in HBsAg- or anti-HCV-positive people from the Republic of Moldova. Arch Virol 163, 431–438 (2018). https://doi.org/10.1007/s00705-017-3632-6

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  • DOI: https://doi.org/10.1007/s00705-017-3632-6