Current Gastroenterology Reports

, Volume 14, Issue 1, pp 37–46 | Cite as

Is There Any Value to Hepatitis B Virus Genotype Analysis?

Liver (BR Bacon, Section Editor)

Abstract

Hepatitis B may cause a varying spectrum of diseases ranging from an asymptomatic or mild anicteric acute illness, to severe or fulminant hepatitis. Similarly, the outcome of chronic hepatitis B is variable. Viral factors associated with outcome of chronic hepatitis B virus (HBV) infection include hepatitis B e antigen status, HBV DNA, genotype, and HBV variants. HBV genotypes and subgenotypes have been associated with differences in clinical and virological characteristics, indicating that they may play a role in the virus-host relationship. A total of ten hepatitis B virus genotypes have been defined with a distinct geographical distribution. Hitherto, genotypes A, B, C and D have been studied most extensively. The HBV genotype appears to influence not only the natural history of HBV related liver disease but also the response to HBV treatment. HBV genotypes are also linked with both core promoter and BCP mutations. Progression to chronic infection appears to occur more frequently following acute infection with genotypes A and D than with the other studied genotypes. Genotypes A and B appear to have higher rates of spontaneous HBeAg seroconversion. More advanced liver disease and progression to HCC is more often seen in chronic infection with genotypes C and D in contrast to genotypes A and B. More specifically, genotypes A1, C, B2–B5 and H appear to be associated with more serious complications than genotypes A2, B1 and B6. These observations suggest important pathogenic differences between HBV genotypes. Genotypes A and B have higher response rates to interferon based therapy than genotypes C and D. Knowledge of HBV genotype enables clinicians to identify those patients at increased risk of disease progression whilst aiding the selection of appropriate antiviral therapy. Genotyping and monoclonal subtyping can provide useful information for epidemiological studies. In conclusion, genotyping of chronic HBV infections can help practicing physicians identify those at risk of disease progression and determine optimal anti-viral therapy.

Keywords

Hepatitis B Genotype Geography Transmission Resistance Natural history Therapy Interferon Nucleos(t)ide Seroconversion Hepatocellular cancer 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis. 2002;2:395–403.PubMedCrossRefGoogle Scholar
  2. 2.
    Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48:335–52.PubMedCrossRefGoogle Scholar
  3. 3.
    • Liang TJ: Hepatitis B: the virus and the disease. Hepatology 2009;49 (Suppl):S13–S21. A broad overview of the lifecycle and replication of hepatitis B virus and spectrum of disease. PubMedCrossRefGoogle Scholar
  4. 4.
    Blumberg BS, Alter HJ, Visnich S. A “new” antigen in leukemia sera. JAMA. 1965;191:541–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Orito E, Mizokami M, Ina Y, et al. Host–independant evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences. Proc Natl Acad Sci USA. 1989;86:7059–62.PubMedCrossRefGoogle Scholar
  6. 6.
    Courouce-Pauty AM, Lemaire JM, Roux JF. New Hepatitis B surface antigen subtypesinside the ad category. Vox Sang. 1978;35:304–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Okamoto H, Tsuda F, Sakugawa H, et al. Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes. J Gen Virol. 1988;69:2575–83.PubMedCrossRefGoogle Scholar
  8. 8.
    Norder H, Hammas B, Lofdahl S, et al. Comparision of the amino acid sequences of nine difference serotypes of hepatitis B surface antigen and genomic classification of the corresponding hepatitis B virus strains. J Gen Virol. 1992;73:1201–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Stuyver L, De Gendt S, Van Geyt C, et al. A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. J Gen Virol. 2000;81:67–74.PubMedGoogle Scholar
  10. 10.
    Arauz-Ruiz P, Norder H, Robertson BH, Magnius LO. Genotype H: a new Amerindian genotype of hepatitis B virus revealed in central America. J Gen Virol. 2002;83:2059–73.PubMedGoogle Scholar
  11. 11.
    Tran TT, Trinh TN, Abe K. New complex recombinant genotype of hepatitis B virus identified in Vietnam. J Virol. 2008;82:5657–63.PubMedCrossRefGoogle Scholar
  12. 12.
    Tatematsu K, Tanaka Y, Kurbanov F, et al. A genetic variant of hepatitis B virus divergent from known human and ape genotypes isolated from a Japanese patient and provisionally assigned to new genotype J. J Virol. 2009;83:10538–47.PubMedCrossRefGoogle Scholar
  13. 13.
    Ohba KI, Mizokami M, Ohno T, et al. Relationships between serotypes and genotypes of hepatitis B virus: Genetic classification of HBV by use of surface genes. Virus Research. 1995;39(1):25–34.PubMedCrossRefGoogle Scholar
  14. 14.
    • Guirgis BS, Abbas RO, Azzazy HM: Hepatitis B virus genotyping: current methods and clinical implications. Int J Infect Dis 2010;14(11):e941–e953. A concise outline of the current genotyping techniques including their advantages and limitations. PubMedCrossRefGoogle Scholar
  15. 15.
    Ma Y, Ding Y, Juan F, Dou XG. Genotyping the hepatitis B virus with a fragment of the HBV DNA polymerase gene in Shenyang, China. Virol J. 2011;8:315–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Jiang SZ, Gao ZY, Li T, et al. T3098C and T53C mutations of HBV genotype C is associated with HBV infection progress. Biomed Environ Sci. 2009;22(6):511–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Ou J, Laub O, Rutter W. Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen. Proc Natl Acad Sci USA. 1986;83:1578–82.PubMedCrossRefGoogle Scholar
  18. 18.
    Carman WF, Jacyna MR, Hadziyannis S, et al. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet. 1989;2:588–91.PubMedCrossRefGoogle Scholar
  19. 19.
    Li J-S, Tong S-P, Wen Y-M, et al. Hepatitis B virus genotype A rarely circulates as an HBe- minus mutant: Possible contribution of a single nucleotide in the precore region. J Virol. 1993;67:5402–10.PubMedGoogle Scholar
  20. 20.
    Mangia A, Chung YH, Hoofnagle JH, et al. Pathogenesis of chronic liver disease in patients with chronic hepatitis B virus infection without serum HBeAg. Dig Dis Sci. 1996;41(12):2447–52.PubMedCrossRefGoogle Scholar
  21. 21.
    Stuyver LJ, Locarnini SA, Lok A, et al. Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region. Hepatology. 1901;33(3):751–7.CrossRefGoogle Scholar
  22. 22.
    Chan HL, Hussain M, Lok AS. Different hepatitis B virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversion. Hepatology. 1999;29(3):976–84.PubMedCrossRefGoogle Scholar
  23. 23.
    Takahashi K, Akahane Y, Hino K, et al. Hepatitis B virus genomic sequence in the circulation of hepatocellular carcinoma patients: comparative analysis of 40 full-length isolates. Arch Virol. 1998;143(12):2313–26.PubMedCrossRefGoogle Scholar
  24. 24.
    Friedt M, Gerner P, Lausch E, et al. Mutations in the basic core promotor and the precore region of hepatitis B virus and their selection in children with fulminant and chronic hepatitis B. Hepatology. 1999;29(4):1252–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Lindh M, Hannoun C, Dhillon AP, et al. Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers. J Infect Dis. 1999;179(4):775–82.PubMedCrossRefGoogle Scholar
  26. 26.
    Lindh M, Gustavson C, Mårdberg K, et al. Mutation of nucleotide 1,762 in the core promoter region during hepatitis B e seroconversion and its relation to liver damage in hepatitis B e antigen carriers. J Med Virol. 1998;55(3):185–90.PubMedCrossRefGoogle Scholar
  27. 27.
    Cho EY, Choi CS, Cho JH, Kim HC. Association between Hepatitis B Virus X Gene Mutations and Clinical Status in Patients with Chronic Hepatitis B Infection. Gut Liver. 2011;5(1):70–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Lee JH, Han KH, Lee JM, et al. Impact of hepatitis B virus (HBV) x gene mutations on hepatocellular carcinoma development in chronic HBV infection. Clin Vaccine Immunol. 2011;18(6):914–21.PubMedCrossRefGoogle Scholar
  29. 29.
    Swenson PD, Van Geyt C, Alexander ER, et al. Hepatitis B virus genotypes and HBsAg subtypes in refugees and injection drug users in the United States determined by LiPA and monoclonal EIA. J Med Virol. 2001;64(3):299–304.CrossRefGoogle Scholar
  30. 30.
    • Kurbanov F, Tanaka Y, Mizokami M: Geographical and genetic diversity of the human hepatitis B virus. Hepatology Research 2010;40:14–30. Comprehensive review of the geographical distribution of genetic variants of hepatitis B and criteria for the identification of new genotypes and subtypes. PubMedCrossRefGoogle Scholar
  31. 31.
    Andernach IE, Nolte C, Pape JW, Muller CP. Slave trade and hepatitis B virus genotypes and subgenotypes in Haiti and Africa. Emerg Infect Dis. 2009;15(8):1222–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Dupinay T, Restorp K, Leutscher P, et al. High prevalence of hepatitis B virus genotype E in Northern Madagascar indicates a West-African lineage. J Med Virol. 2010;82(9):1515–26.PubMedCrossRefGoogle Scholar
  33. 33.
    Andernach IE, Hubschen JM, Muller CP. Hepatitis B virus: the genotype E puzzle. Rev Med Virol. 2009;19(4):231–40.PubMedCrossRefGoogle Scholar
  34. 34.
    Garmiri P, Loua A, Haba N, et al. Deletions and recombinations in the core region of hepatitis B virus genotype E strains from asymptomatic blood donors in Guinea, west Africa. J Gen Virol. 2009;90(Pt 10):2442–51.PubMedCrossRefGoogle Scholar
  35. 35.
    Hu XL, Margolis HS, Purcell RH, et al.: Identification of hepatitis B virus indigenous to chimpanzees. Proceedings of the National Academy of Sciences of the United States of America 2000;97(4):1661–4.Google Scholar
  36. 36.
    Norder H, Ebert JW, Fields HA, et al. Complete sequencing of a gibbon hepatitis B virus genome reveals a unique genotype distantly related to the chimpanzee hepatitis B virus. Virology. 1996;218(1):214–23.PubMedCrossRefGoogle Scholar
  37. 37.
    Takahashi K, Brotman B, Usuda S, et al. Full-genome sequence analyses of hepatitis B virus (HBV) strains recovered from chimpanzees infected in the wild: Implications for an origin of HBV. Virology. 2000;267(1):58–64.PubMedCrossRefGoogle Scholar
  38. 38.
    MacDonald DM, Holmes EC, Lewis JC, Simmonds P. Detection of hepatitis B virus infection in wild-born chimpanzees (Pan troglodytes verus): Phylogenetic relationships with human and other primate genotypes. J Virol. 2000;74(9):4253–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization practices (ACIP) part 1: immunization of infants, children and adolescents. MMWR Recomm Rep. 2005;54(RR-16):1–31.PubMedGoogle Scholar
  40. 40.
    Beasley RP, Hwang LY, Lee GC, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet. 1983;2(8359):1099–102.PubMedCrossRefGoogle Scholar
  41. 41.
    Mast EE, Weinbaum CM, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization practices (ACIP) part 1: immunization of infants, children and adolescents. MMWR Recomm Rep. 2006;55(RR16):1–25.PubMedGoogle Scholar
  42. 42.
    Livingston SE, Simonetti J, Bulkow L, et al. Clearance of Hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D and F. Gastroenterology. 2007;133:1452–7.PubMedCrossRefGoogle Scholar
  43. 43.
    Kao JH, Chen PJ, Lai MY, Chen DS. Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriers. J Med Virol. 2004;72:363–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Chu CJ, Hussain M, Lok AS. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology. 2002;122:1756–62.PubMedCrossRefGoogle Scholar
  45. 45.
    • Wen WH, Chen HL, Ni YH, et al.: Secular trend of the viral genotype distribution in children with chronic hepatitis B virus infection after universal infant immunization. Hepatology 2011;53(2):429–36. Study outlining the change in hepatitis B genotypes following the introduction of mass immunization in Taiwan and the consequences for vertical transmission. PubMedCrossRefGoogle Scholar
  46. 46.
    Sanchez-Tapias JM, Costa J, Mas A, et al. Influence of hepatitis B virus genotype on the long term outcome of chronic hepatitis B in western patients. Gastroenterology. 2002;123:1848–56.PubMedCrossRefGoogle Scholar
  47. 47.
    Yuen MF, Wong DK, Sablon E, et al.: HBsAg seroclearance in chronic hepatitis B in the Chinese: virological, histological, and clinical aspects. Hepatology 2004;39:1694–701. [Published erratum appears in Hepatology 2004;40:767].Google Scholar
  48. 48.
    Hadziyannis SJ. Natural history of chronic hepatitis B in Euro-Mediterranean and African Countries. J Hepatol. 2011;55(1):183–91.PubMedCrossRefGoogle Scholar
  49. 49.
    Kew MC, Kramvis A, Yu MC, et al. Increased hepatocarcinogenic potential of hepatitis B virus genotype in Bantu-speaking sub-Saaran Africans. J Med Virol. 2005;75:513–21.PubMedCrossRefGoogle Scholar
  50. 50.
    Kimbi G, Kramvis A, Kew M. Distinctive sequence characteristics from subgenotype A1isolates of hepatitis B virus from South Africa. J Gen Virol. 2004;85:1211–20.PubMedCrossRefGoogle Scholar
  51. 51.
    Kew MC. Hepatocellular carcinoma in African Blacks: Recent progress in etiology and pathogenesis. World J Hepatol. 2010;2(2):65–73.PubMedGoogle Scholar
  52. 52.
    Livingston SE, Simonetti JP, McMahon BJ, et al. Hepatitis B virus genotypes in Alaska Native people with hepatocellular carcinoma: preponderance of genotype F. J Infect Dis. 2007;195:5–11.PubMedCrossRefGoogle Scholar
  53. 53.
    Saugauchi F, Orito E, Ichida T, et al. Epidemiologic and virological characteristics of hepatitis B virus genotype B having the recombination with genotype C. Gastroenterology. 2003;124:925–32.CrossRefGoogle Scholar
  54. 54.
    Ozasa A, Tanaka Y, Orito E, et al. Influence of genotypesand precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection. Hepatology. 2006;44:326–34.PubMedCrossRefGoogle Scholar
  55. 55.
    Lee CM, Chen CH, Lu SN, et al. Prevalence an clinical implications of hepatitis B virus genotypes in southern Taiwan. Scan J Gastroenterol. 2003;38:95–101.CrossRefGoogle Scholar
  56. 56.
    Tangkijvanich P, Mahachai V, Komolmit P, et al. Hepatitis B virus genotypes and hepatocellular carcinoma in Thailand. Word J Gastroenterol. 2005;11(15):2238–43.Google Scholar
  57. 57.
    Chu CM, Laiw YF. Genotype C hepatitis B virusinfection is associated with higher risk of reactivation of hepatitis B and progression to cirrhosis than genotype B: a longitudinal study of hepatitis B e antigen-positive patients with normal aminotransferase levels a baseline. J Hepatol. 2005;43:411–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Yuen MF, Sablon E, Yuan HJ, et al. Significance of hepatitis B genotype in acute exacerbation, HBeAg seroconversion, cirrhosis-related complications, and hepatocellular carcinoma. Hepatology. 2003;37:562–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Zhang AM, Wang HF, Wang HB, et al. Association between HBV genotype and chronic/severe liver disease with HBV infection in Chinese patients. Chin J Exp Clin Virol. 2010;24(3):178–80.Google Scholar
  60. 60.
    Yang HI, Yeh SH, Chen PJ, et al. Associations between hepatitis B virus genotype and mutants and the risk of hepatocellular carcinoma. Journal of the National Cancer Institute. 2008;100(16):1134–43.PubMedCrossRefGoogle Scholar
  61. 61.
    Orito E, Mizokami M, Sakugawa H, et al. A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C. Hepatology. 2001;33(1):218–23.PubMedCrossRefGoogle Scholar
  62. 62.
    Kao JH, Chen PJ, Lai MY, Chen DS. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology. 2000;118(3):554–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Qin Y, Tang X, Garcia T, et al.: Hepatitis B virus genotype C isolates with wild-type core promoter sequence replicate less efficiently than genotype B isolates but possess higher virion secretion capacity. J Virol 2011;%20.Google Scholar
  64. 64.
    Liang TJ, Mok KT, Liu SI, et al. Hepatitis B genotype C correlated with poor surgical outcomes for hepatocellular carcinoma. J Am Coll Surg. 2010;211(5):580–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Chan HL, Tse AM, Mo F, et al. High viral load and hepatitis B virus subtype Ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol. 2008;26(2):177–82.PubMedCrossRefGoogle Scholar
  66. 66.
    Liu S, Zhang H, Gu C, et al. Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: a meta-analysis. J Natl Cancer Inst. 2009;101:1066–82.PubMedCrossRefGoogle Scholar
  67. 67.
    Yin JH, Zhao J, Zhang HW, et al. HBV genotype C is independently associated with cirrhosis in community-based population. World J Gastroenterol. 2010;16(3):379–83.PubMedCrossRefGoogle Scholar
  68. 68.
    • Ren X, Xu Z, Liu Y, et al.: Hepatitis B virus genotype and basal core promoter/precore mutations are associated with hepatitis B-related acute-on-chronic liver failure without pre-existing liver cirrhosis. J Viral Hepat 2010;17(12):887–95. A study of patients with hepatitis B and acute -on-chronic liver failure which gives credence to the concept that both hepatitis B genotype and BCP/PC mutations are associated with more severe disease phenotype. PubMedCrossRefGoogle Scholar
  69. 69.
    Cho EY, Kim HC, Choi CS, et al. Nucleotide changes related to hepatocellular carcinoma in the enhancer 1/x-promoter of hepatitis B virus subgenotype C2 in cirrhotic patients. Cancer Sci. 2010;101(8):1905–12.PubMedCrossRefGoogle Scholar
  70. 70.
    Zacharakis GH, Koskinas J, Kotsiou S, et al.: Natural history of chronic HBV infection: a cohort with up to 12 years follow-up in North Greece (part of the Interrg I-II/EC-Project). J Med Virol 2005;173–179.Google Scholar
  71. 71.
    Sharma S, Sharma B, Singla B, et al. Clinical significance of genotypes and precore/basal core promoter mutations in HBV related chronic liver disease patients in North India. Dig Dis Sci. 2010;55:794–802.PubMedCrossRefGoogle Scholar
  72. 72.
    Arankalle VA, Gandhi S, Lole KS, et al. An outbreak of hepatitis B with high mortality in India: association with precore, basal core promoter mutants and improperly sterilized syringes. J Viral Hepat. 2011;18(4):e20–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Suzuki S, Sugauchi F, Orito E, et al. Distribution of hepatitis B virus (HBV) genotypes among HBV carriers in the Cote d’Ivoire: complete genome sequence and phylogenetic relatedness of HBV genotype E. J Med Virol. 2003;69:459–65.PubMedCrossRefGoogle Scholar
  74. 74.
    Kato H, Orito E, Gish RG, et al. Hepatitis B e antigen in sera from individuals infected with hepatitis B virus of genotype G. Hepatology. 2002;35:922–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Lacombe K, Massari V, Girard PM, et al. Major role of hepatitis B genotypes in liver fibrosis during coinfection with HIV. AID. 2006;20(3):419–27.CrossRefGoogle Scholar
  76. 76.
    Dao DY, Balko J, Attar N, et al. Hepatitis B virus genotype G: Prevalence and impact in patients co-infected with human immunodeficiency virus. J Med Virol. 2011;83(9):1551–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Schaefer S. Hepatitis B virus: significance of genotypes. J Viral Hepat. 2005;12:111–24.PubMedCrossRefGoogle Scholar
  78. 78.
    Kiesslich D, Crispim MA, Santos C, et al. Influence of hepatitis B virus (HBV) genotype on the clinical course of disease in patients coinfected with HBV and hepatitis delta virus. J Infect Dis. 2009;199(11):1608–11.PubMedCrossRefGoogle Scholar
  79. 79.
    Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50(3):661–2.PubMedCrossRefGoogle Scholar
  80. 80.
    Liaw YF, Leung N, Kao JH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2:263–83.PubMedCrossRefGoogle Scholar
  81. 81.
    Liver European Association For The Study Of The. EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227–42.CrossRefGoogle Scholar
  82. 82.
    Kao JH, Wu NH, Chen PJ, et al. Hepatitis B genotypes and the response to interferon therapy. J Hepatol. 2000;33:998–1002.PubMedCrossRefGoogle Scholar
  83. 83.
    Hou J, Schilling R, Janssen HLA. Molecular characteristics of hepatitis B virus genotype A confer a higher response to interferon treatment. J Hepatol. 2001;34(1):15.Google Scholar
  84. 84.
    Wai CT, Chu CJ, Hussain M, Lok AS. HBV genotype B is associated with better response to interferon therapy in HBeAg(+) chronic hepatitis than genotype C. Hepatology. 2002;36:1425–30.PubMedGoogle Scholar
  85. 85.
    Erhardt A, Blondin D, Hauck K, et al. Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D. Gut. 2005;54:1009–13.PubMedCrossRefGoogle Scholar
  86. 86.
    Cooksley WG, Piratvisuth T, Lee SD, et al. Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat. 2003;10(4):298–305.PubMedCrossRefGoogle Scholar
  87. 87.
    Craxi A, Cooksley WG. Pegylated interferons for chronic hepatitis B. Antiviral Res. 2003;60(2):87–9.PubMedCrossRefGoogle Scholar
  88. 88.
    • Chen CH, Lee CM, Hung CH, et al.: Hepatitis B virus genotype B results in better immediate, late and sustained responses to peginterferon-alfa in hepatitis-B-e-antigen-positive patients. J Gastroenterol Hepatol 2011;26(3):461–8. A recent study which emphasises the importance of hepatitis B genotype in treatment response to peginterferon. PubMedCrossRefGoogle Scholar
  89. 89.
    Janssen HL, van Zonneveld M, Senturk H, et al. HBV 99–01 study group; Rotterdam foundation for liver research. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Flink HJ, van Zonneveld M, Hansen BE, et al. HBV 99–01 Study Group. Treatment with Peg-interferon alpha-2b for HBeAg-positive chronic hepatitis B: HBsAg loss is associated with HBV genotype. Am J Gastroenterol. 2006;101:297–303.PubMedCrossRefGoogle Scholar
  91. 91.
    Kao JH, Wu NH, Chen PJ, et al. Hepatitis B genotypes and the response to interferon therapy. J Hepatol. 2000;33(6):998–1002.PubMedCrossRefGoogle Scholar
  92. 92.
    • Wiegand J, Hasenclever D, Tillmann HL: Should treatment of hepatitis B depend on hepatitis B virus genotypes? A hypothesis generated from an explorative analysis of published evidence. Antivir Ther 2008;13:211–20. An overview and meta-analysis of the literature on hepatitis B treatment with interferon or nucleos(tide) analogues. PubMedGoogle Scholar
  93. 93.
    Marcellin P, Bonino F, Lau GK, et al. Peginterferon alfa-2a in HBeAg-negative Chronic Hepatitis B Study Group. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology. 2009;136:2169–79.PubMedCrossRefGoogle Scholar
  94. 94.
    Erhardt A, Göbel T, Ludwig A, et al. Response to antiviral treatment in patients infected with hepatitis B virus genotypes E-H. J Med Virol. 2009;81:1716–20.PubMedCrossRefGoogle Scholar
  95. 95.
    Hansen BE, Buster EH, Steyerberg EW, et al. Prediction of the response to peg-interferon-alfa in patients with HBeAg positive chronic hepatitis B using decline of HBV DNA during treatment. J Med Virol. 2010;82(7):1135–42.PubMedCrossRefGoogle Scholar
  96. 96.
    Hsieh TH, Tseng TC, Liu CJ, et al. Hepatitis B virus genotype B has an earlier emergence of lamivudine resistance than genotype C. Antivir Ther. 2009;14:1157–63.PubMedCrossRefGoogle Scholar
  97. 97.
    Inoue J, Ueno Y, Wakui Y, et al. Four-year study of lamivudine and adefovir combination therapy in lamivudine-resistant hepatitis B patients: influence of hepatitis B virus genotype and resistance mutation pattern. Journal of Viral Hepatitis. 2011;18(3):206–15.PubMedCrossRefGoogle Scholar
  98. 98.
    Wursthorn K, Jung M, Riva A, et al. Kinetics of hepatitis B surface antigen decline during 3 years of telbivudine treatment in hepatitis B e antigen-positive patients. Hepatology. 2010;52(5):1611–20.PubMedCrossRefGoogle Scholar
  99. 99.
    Hsieh TH, Tseng TC, Liu CJ, et al. Hepatitis B virus genotype B has an earlier emergence of lamivudine resistance than genotype C. Antivir Ther. 2009;14(8):1157–63.PubMedCrossRefGoogle Scholar
  100. 100.
    Tabernero D, Sanchez MJ, Homs M, et al. Main mutations in the hepatitis B virus basic core promoter (A1762T/G1764A) before HBeAg loss are markers that identify patients who will require long-term treatment. Aliment Pharmacol Ther. 2010;32(1):97–104.PubMedGoogle Scholar
  101. 101.
    Fujisaki S, Yokomaku Y, Shiino T, et al. Outbreak of infections by hepatitis B virus genotype A and transmission of genetic drug resistance in patients coinfected with HIV-1 in Japan. J Clin Microbiol. 2011;49(3):1017–24.PubMedCrossRefGoogle Scholar
  102. 102.
    Wei C, Chong YT, Wen JZ, et al. Characterization of hepatitis virus B isolated from a multi-drug refractory patient. Virus Research. 2011;155(1):254–8.PubMedCrossRefGoogle Scholar
  103. 103.
    McMahon BJ. The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B. Hepatol Int. 2009;3(2):334–42.PubMedCrossRefGoogle Scholar
  104. 104.
    Yuen MF, Tanaka Y, Fong DY, et al. Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol. 2009;50:80–8.PubMedCrossRefGoogle Scholar
  105. 105.
    Wong VW, Chan SL, Mo F, et al. Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers. J Clin Oncol. 2010;28:1660–5.PubMedCrossRefGoogle Scholar
  106. 106.
    • Yang HI, Sherman M, Su J, et al.: Nomograms for risk of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. J. Clin. Oncol. 2010;28:2437–44. [13]. A model based upon the REVEAL-HBV study cohort data identifying which viral and host factors are associated with the development of HBV associated HCC. PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Centre for HepatologyUniversity College London Royal Free CampusLondonUK

Personalised recommendations