Journal of Gastroenterology

, Volume 44, Issue 6, pp 568–576 | Cite as

A phylogenetic study of hepatitis B virus in chronically infected Brazilian patients of Western and Asian descent

  • Cintia Mendes Clemente
  • Flair José Carrilho
  • João Renato Rebello Pinho
  • Suzane Kioko Ono-Nita
  • Luiz Caetano Da Silva
  • Regina Célia Moreira
  • Marcílio Figueiredo Lemos
  • Isabel Maria Vicente Guedes de Carvalho Mello
Original Article—Liver, Pancreas, and Biliary Tract



Hepatitis B virus (HBV) causes one of the most important chronic viral infections worldwide. HBV is classified into eight genotypes whose epidemiology varies geographically. In Brazil, genotypes A, D, and F are more frequent, while in East Asia, genotypes B and C predominate. Several studies showed that immigrants retain the HBV infection pattern of their ancestral country.


To identify HBV genotypes infecting chronic carriers in Brazilian families of Western and Asian descent by Hepatitis B surface antigen gene sequencing and analyze the route of viral transmission by phylogenetic analysis of viral sequences.


Eighty-seven people chronically infected with HBV were separated into two groups: Western descent (27) and Asian descent (60). Surface and pre-core/core genes were amplified from serum HBV-DNA and sequences were subjected to phylogenetic analysis.


HBV genotype A was found in 74% of Western subjects, while genotype C was found in 94% of Asian patients. Thirty-eight percent of Western families were infected with HBV with similar pre-core/core sequences, while only 25% of Asian families showed similarity in these sequences.


Phylogenetical analysis of pre-core/core HBV gene suggested intra-familial transmission of HBV in 38% of Western families and 25% of Asian families. Analysis of HBsAg gene sequences helped to define the HBV genotype but did not allow inferring route of transmission as its sequences showed a smaller phylogenetic signal than pre-core/core sequences. Chronic HBV carriers of Asian descent born in or living in Brazil were infected with the same HBV genotype predominant in their ancestral country.


Hepatitis B Disease transmission Genotype Phylogeny Family 



FAPESP—Fundação de Amparo à Pesquisa do Estado de São Paulo (Grants 00/00998/1 and 0011457/1 Viral Genetic Diversity Network) and Alves de Queiroz Family Fund for Research.


  1. 1.
    Lavanchy D. Epidemiology. In: Thomas HC, Lemon S, Zuckerman AJ, editors. Viral Hepatitis. 3rd ed. Malden: Blackwell; 2005. p. 181–92.Google Scholar
  2. 2.
    Kann M, Gerlich WH. Structure and molecular virology. In: Thomas HC, Lemon S, Zuckerman AJ, editors. Viral Hepatitis. 3rd ed. Malden: Blackwell; 2005. p. 149–80.Google Scholar
  3. 3.
    Sitnik R, Pinho JRR, Bertolini DA, Bernardini AP, da Silva LC, Carrilho FJ. Hepatitis B virus genotypes and precore and core mutations in Brazilian patients. J Clin Microbiol. 2004;42:2455–660.PubMedCrossRefGoogle Scholar
  4. 4.
    Kidd-Ljunggren K, Miyakawa Y, Kidd AH. Genetic variability in hepatitis B viruses. J Gen Virol. 2002;83:1267–80.PubMedGoogle Scholar
  5. 5.
    Carrilho FJ, Mendes-Corrêa MCJ. Magnitude of hepatitis B and C in Latin America. In: Schinazi RF, Sommadossi J-P, Thomas HC, editors. Therapies for Viral Hepatitis. London: International Medical Press; 1998. p. 25–34.Google Scholar
  6. 6.
    Chu CJ, Keeffe EB, Han SH, Perrillo RP, Min AD, Soldevila-Pico C, et al. Hepatitis B virus genotypes in the United States: results of a nationwide study. Gastroenterology. 2003;125:444–51.PubMedCrossRefGoogle Scholar
  7. 7.
    Dumpis U, Holmes EC, Mendy M, Hill A, Thursz M, Hall A, et al. Transmission of hepatitis B infection in Gambian families revealed by phylogenetic analysis. J Hepatol. 2001;35:99–104.PubMedCrossRefGoogle Scholar
  8. 8.
    Santantonio T, Jung MC, Pastore G, Angarano G, Günther S, Will H. Familial clustering of HBV pre-C and pre-S mutants. J Hepatol. 1997;26:221–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Lin CL, Kao JH, Chen BF, Chen PJ, Lai MY, Chen DS. Application of hepatitis B virus genotyping and phylogenetic analysis in intrafamilial transmission of hepatitis B virus. Clin Infect Dis. 2005;41:1576–81.PubMedCrossRefGoogle Scholar
  10. 10.
    Kaneko S, Feinstone SM, Miller RH. Rapid and sensitive method for the detection of serum hepatitis B virus DNA using the polymerase chain reaction technique. J Clin Microbiol. 1989;27:1930–3.PubMedGoogle Scholar
  11. 11.
    Takahashi K, Aoyama K, Ohno N, Iwata K, Akahane Y, Baba K, et al. The precore/core promoter mutant (T1762A1764) of hepatitis B virus: clinical significance and an easy method for detection. J Gen Virol. 1995;76:3159–64.PubMedCrossRefGoogle Scholar
  12. 12.
    Strimmer K, Von Haeseler A. Likelihood–mapping: a simple method to visualize phylogenetic content of a sequence alignment. Proc Natl Acad Sci USA. 1997;94:6815–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Hall T. BioEdit, version 6.0.7. Ibis therapeutics. Carlsbad, 2004.Google Scholar
  14. 14.
    Swofford DL. PAUP* Phylogenetic analysis using Parsimony (*and Other Methods), Version 4b10. Sinauer. Sunderland, 2002.Google Scholar
  15. 15.
    Posada D, Crandal KA. Modeltest: testing the model of DNA substitution. Bioinformatics. 1998;14:817–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Carrilho FJ, Ono-Nita SK, Cardoso RA, Cancado EL, Pinho JR, Alves VA, et al. A prospective study of hepatitis B virus markers in patients with chronic HBV infection from Brazilian families of Western and Asian origin. Braz J Med Biol Res. 2005;38:1399–408.PubMedCrossRefGoogle Scholar
  17. 17.
    Ono-Nita SK, Carrilho FJ, Cardoso RA, Nita ME, da Silva LC. Searching for chronic hepatitis B patients in a low prevalence area–role of racial origin. BMC Fam Pract. 2004;5:7.PubMedCrossRefGoogle Scholar
  18. 18.
    Guidotti LG, Ishikawa T, Hobbs MV, Matzke B, Schreiber R, Chisari FV. Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity. 1996;4:25–36.PubMedCrossRefGoogle Scholar
  19. 19.
    Khan A, Tanaka Y, Saito H, Ebinuma H, Sekiguchi H, Iwama H, et al. Transmission of hepatitis B virus (HBV) genotypes among Japanese immigrants and natives in Bolivia. Virus Res. 2008;132:174–80.PubMedCrossRefGoogle Scholar
  20. 20.
    Zhong M, Hou J, Luo K. Identification of vertical transmission of hepatitis B virus from mother to children by direct sequencing a segment of surface gene of hepatitis B virus. Zhonghua Yi Xue Za Zhi. 1996;76:194–6.PubMedGoogle Scholar
  21. 21.
    Martinson FE, Weigle KA, Royce RA, Weber DJ, Suchindran CM, Lemon SM. Risk factors for horizontal transmission of hepatitis B virus in a rural district in Ghana. Am J Epidemiol. 1998;147:478–87.PubMedGoogle Scholar
  22. 22.
    Alarka US, Greene S, Lok AS. Detection of precore hepatitis B virus mutants in asymptomatic HBsAg-positive family members. Hepatology. 1994;19:1366–70.CrossRefGoogle Scholar
  23. 23.
    Cacciola I, Cerenzia G, Pollicino T, Squadrito G, Castellaneta S, Zanetti AR. Genomic heterogeneity of hepatitis B virus (HBV) and outcome of perinatal HBV infection. J Hepatol. 2002;36:426–32.PubMedCrossRefGoogle Scholar
  24. 24.
    Thomas HC, Carman WF. Envelope and precore/core variants of hepatitis B virus. Gastroenterol Clin North Am. 1994;23:499–514.PubMedGoogle Scholar
  25. 25.
    Zampino R, Lobello S, Chiaramonte M, Venturi-Pasini C, Dumpis U, Thursz M, et al. Intra-familial transmission of hepatitis B virus in Italy: phylogenetic sequence analysis and amino-acid variation of the core gene. J Hepatol. 2002;36:248–53.PubMedCrossRefGoogle Scholar
  26. 26.
    Sugauchi F, Mizokami M, Orito E, Sugauchi F, Mizokami M, Orito E, et al. Molecular evolutionary analysis of the complete nucleotide sequence of hepatitis B virus (HBV) in a case of HBV infection acquired through a needlestick accident. Clin Infect Dis. 2000;31:1195–201.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  • Cintia Mendes Clemente
    • 1
  • Flair José Carrilho
    • 1
  • João Renato Rebello Pinho
    • 1
    • 2
  • Suzane Kioko Ono-Nita
    • 1
  • Luiz Caetano Da Silva
    • 1
  • Regina Célia Moreira
    • 3
  • Marcílio Figueiredo Lemos
    • 3
  • Isabel Maria Vicente Guedes de Carvalho Mello
    • 1
    • 4
  1. 1.Departmento de Gastroenterologia, Faculdade de MedicinaUniversidade de São PauloSão PauloBrazil
  2. 2.Laboratório de Hepatologia e Gastroenterologia TropicalInstituto de Medicina Tropical da Universidade de São PauloSão PauloBrazil
  3. 3.Serviço de Virologia, Instituto Adolfo LutzSão PauloBrazil
  4. 4.Laboratório de Imunologia ViralInstituto ButantanSão PauloBrazil

Personalised recommendations