Current Hepatitis Reports

, Volume 5, Issue 1, pp 5–13 | Cite as

HBV genotypes: Epidemiology and implications regarding natural history



Hepatitis B virus (HBV) infection is a global health problem and eight different genotypes (A to H) have been identified. The epidemiology of HBV genotypes and their implications for the natural history of HBV infection have become increasingly recognized. Genotypes A and D are common in Europe, whereas genotypes B and C are prevalent in Asia. In Asian countries, genotype B is shown to be associated with spontaneous hepatitis B e antigen (HBeAg) seroconversion at a younger age, less active liver disease, slower progression to cirrhosis, and less frequent development of hepatocellular carcinoma than genotype C. In Western countries, genotype D is shown to have a lower positivity of HBeAg, less chance of sustained remission after seroconversion, and a less favorable prognosis than genotype A. Thus, clinical differences do exist among HBV genotypes, and further research is needed on the molecular mechanisms underlying the clinical phenotypes of different HBV genotypes.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Kao JH, Chen DS: Global control of hepatitis B virus. Lancet Infect Dis 2002, 2:395–403.PubMedCrossRefGoogle Scholar
  2. 2.
    Kao JH, Chen DS: Overview of hepatitis B and C viruses. In Infectious Causes of Cancer: Targets for Intervention. Edited by Goedert JJ. Totowa: Humana Press; 2000:313–330.CrossRefGoogle Scholar
  3. 3.
    Ganem D, Prince AM: Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med 2004, 350:1118–1129.PubMedCrossRefGoogle Scholar
  4. 4.
    Chisari FV, Ferrari C: Hepatitis B immunopathogenesis. Annu Rev Immunol 1995, 13:29–60.PubMedCrossRefGoogle Scholar
  5. 5.
    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
  6. 6.
    Wai CT, Chu CJ, Hussain M, et al.: HBV genotype B is associated with better response to interferon therapy in HBeAg (+) chronic hepatitis than genotype C. Hepatology 2002, 36:1425–1430.PubMedGoogle Scholar
  7. 7.
    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, 10:298–305.PubMedCrossRefGoogle Scholar
  8. 8.
    Janssen HL, van Zonneveld M, Senturk H, et al.: Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet 2005, 365:123–129.PubMedCrossRefGoogle Scholar
  9. 9.
    Kao JH, Liu CJ, Chen DS: Hepatitis B viral genotypes and lamivudine resistance. J Hepatol 2002, 36:303–304.PubMedCrossRefGoogle Scholar
  10. 10.
    Yuen MF, Wong DK, Sablon E, et al.: Hepatitis B virus genotypes B and C do not affect the antiviral response to lamivudine. Antivir Ther 2003, 8:531–534.PubMedGoogle Scholar
  11. 11.
    Westland C, Delaney WT, Yang H, et al.: Hepatitis B virus genotypes and virologic response in 694 patients in phase III studies of adefovir dipivoxil. Gastroenterology 2003, 125:107–116.PubMedCrossRefGoogle Scholar
  12. 12.
    Kao JH: Hepatitis B viral genotypes: clinical relevance and molecular characteristics. J Gastroenterol Hepatol 2002, 17:643–650.PubMedCrossRefGoogle Scholar
  13. 13.
    Yeh SH, Tsai CY, Kao JH, et al.: Quantification and genotyping of hepatitis B virus in a single reaction by real-time PCR and melting curve analysis. J Hepatol 2004, 41:659–666.PubMedCrossRefGoogle Scholar
  14. 14.
    Chen BF, Chen PJ, Jow GM, et al.: High prevalence of mixed genotype infections in hepatitis B virus infected intravenous drug users. J Med Virol 2004, 74:536–542.PubMedCrossRefGoogle Scholar
  15. 15.
    Bartholomeusz A, Schaefer S: Hepatitis B virus genotypes: comparison of genotyping methods. Rev Med Virol 2004, 14:3–16.PubMedCrossRefGoogle Scholar
  16. 16.
    Norder H, Courouce AM, Coursaget P, et al.: Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology 2004, 47:289–309. This is the largest phylogenetic analysis study of HBV strains (234 complete genomes and 631 HBsAg genes) that provides the geographic distribution of HBV genotypes and subgenotypes worldwide.PubMedCrossRefGoogle Scholar
  17. 17.
    Kao JH, Chen PJ, Lai MY, Chen DS: Clinical and virological aspects of blood donors infected with hepatitis B virus genotypes B and C. J Clin Microbiol 2002, 40:22–25.PubMedCrossRefGoogle Scholar
  18. 18.
    Kao JH, Hsu HM, Shau WY, et al.: Universal hepatitis B vaccination and the decreased mortality from fulminant hepatitis in infants in Taiwan. J Pediatr 2001, 139:349–352.PubMedCrossRefGoogle Scholar
  19. 19.
    Chen BF, Kao JH, Liu CJ, et al.: Genotypic dominance and novel recombinations in HBV genotype B and C co-infected intravenous drug users. J Med Virol 2004, 73:13–22.PubMedCrossRefGoogle Scholar
  20. 20.
    Poland GA, Jacobson RM: Clinical practice: prevention of hepatitis B with the hepatitis B vaccine. N Engl J Med 2004, 351:2832–2838.PubMedCrossRefGoogle Scholar
  21. 21.
    Kao JH, Chen DS: Recent updates in hepatitis vaccination and the prevention of hepatocellular carcinoma. Int J Cancer 2002, 97:269–271.PubMedCrossRefGoogle Scholar
  22. 22.
    Kobayashi M, Suzuki F, Arase Y, et al.: Infection with hepatitis B virus genotype A in Tokyo, Japan during 1976 through 2001. J Gastroenterol 2004, 39:844–850.PubMedCrossRefGoogle Scholar
  23. 23.
    Suzuki Y, Kobayashi M, Ikeda K, et al.: Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan. J Med Virol 2005, 76:33–39.PubMedCrossRefGoogle Scholar
  24. 24.
    Mayerat C, Mantegani A, Frei PC: Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection? J Viral Hepat 1999, 6:299–304.PubMedCrossRefGoogle Scholar
  25. 25.
    Imamura T, Yokosuka O, Kurihara T, et al.: Distribution of hepatitis B viral genotypes and mutations in the core promoter and precore regions in acute forms of liver disease in patients from Chiba, Japan. Gut 2003, 52:1630–1637.PubMedCrossRefGoogle Scholar
  26. 26.
    Liu CJ, Kao JH, Lai MY, et al.: Precore/core promoter mutations and genotypes of hepatitis B virus in chronic hepatitis B patients with fulminant or subfulminant hepatitis. J Med Virol 2004, 72:545–550.PubMedCrossRefGoogle Scholar
  27. 27.
    Wai CT, Fontana RJ, Polson J, et al.: The US Acute Liver Failure Study Group. Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States. J Viral Hepat 2005, 12:192–198.PubMedCrossRefGoogle Scholar
  28. 28.
    Yang HI, Lu SN, Liaw YF, et al.: Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 2002, 347:168–174.PubMedCrossRefGoogle Scholar
  29. 29.
    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, 122:1756–1762. The first report found that HBV genotype B was associated with earlier and frequent HBeAg seroconversion than genotype C in Chinese patients.PubMedCrossRefGoogle Scholar
  30. 30.
    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, 72:363–369.PubMedCrossRefGoogle Scholar
  31. 31.
    Yuen MF, Fung SK, Tanaka Y, et al.: Longitudinal study of hepatitis activity and viral replication before and after HBeAg seroconversion in chronic hepatitis B patients infected with genotypes B and C. J Clin Microbiol 2004, 42:5036–5040.PubMedCrossRefGoogle Scholar
  32. 32.
    Watanabe K, Takahashi T, Takahashi S, et al.: Comparative study of genotype B and C hepatitis B virus-induced chronic hepatitis in relation to the basic core promoter and precore mutations. J Gastroenterol Hepatol 2005, 20:441–449.PubMedCrossRefGoogle Scholar
  33. 33.
    Ni YH, Chang MH, Wang KJ, et al.: Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma. Gastroenterology 2004, 127:1733–1738. This prospective study provided solid evidence that the impact of HBV genotypes on HBeAg seroconversion emerges even in the early phase of chronic HBV infection.PubMedCrossRefGoogle Scholar
  34. 34.
    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, 123:1848–1856. The paper first indicated that long-term outcomes of chronic HBV infection vary with different HBV genotypes in western patients.PubMedCrossRefGoogle Scholar
  35. 35.
    Yuen MF, Wong DK, Sablon E, et al.: HBsAg seroclearance in chronic hepatitis B in the Chinese: virological, histological, and clinical aspects. Hepatology 2004, 39:1694–1701. [Published erratum appears in Hepatology 2004, 40:767.]PubMedCrossRefGoogle Scholar
  36. 36.
    Kao JH, Chen PJ, Lai MY, et al.: Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection. J Clin Microbiol 2002, 40:1207–1209.PubMedCrossRefGoogle Scholar
  37. 37.
    Chan HL, Wong ML, Hui AY, et al.: Hepatitis B virus genotype C takes a more aggressive disease course than hepatitis B virus genotype B in hepatitis B e antigenpositive patients. J Clin Microbiol 2003, 41:1277–1279.PubMedCrossRefGoogle Scholar
  38. 38.
    Sumi H, Yokosuka O, Seki N, et al.: Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease. Hepatology 2003, 37:19–26.PubMedCrossRefGoogle Scholar
  39. 39.
    Kidd-Ljunggren K, Myhre E, Blackberg J: Clinical and serological variation between patients infected with different hepatitis B virus genotypes. J Clin Microbiol 2004, 42:5837–5841.PubMedCrossRefGoogle Scholar
  40. 40.
    Kao JH, Chen PJ, Lai MY, Chen DS: Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 2000, 118:554–559. This leading Taiwanese study suggested that HBV genotypes may influence the natural history of HBV disease progression.PubMedCrossRefGoogle Scholar
  41. 41.
    Kao JH, Chen PJ, Lai MY, Chen DS: Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology 2003, 124:327–334. This report provided further evidence of the role of HBV genotype and basal core promoter mutation in the development of HBVrelated HCC.PubMedCrossRefGoogle Scholar
  42. 42.
    Yuen MF, Tanaka Y, Mizokami M, et al.: Role of hepatitis B virus genotypes Ba and C, core promoter and precore mutations on hepatocellular carcinoma: a case control study. Carcinogenesis 2004, 25:1593–1598.PubMedCrossRefGoogle Scholar
  43. 43.
    Chan HL, Hui AY, Wong ML, et al.: Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Gut 2004, 53:1494–1498.PubMedCrossRefGoogle Scholar
  44. 44.
    Yu MW, Yeh SH, Chen PJ, et al.: Genotype and DNA levels of hepatitis B virus and the risk of hepatocellular carcinoma. J Natl Cancer Inst 2005, 97:265–272. This 14-year prospective study on 4841 Taiwanese male HBV carriers demonstrated the associations of HBV genotype and viral load with HCC risk are additive.PubMedCrossRefGoogle Scholar
  45. 45.
    Mahmood S, Niiyama G, Kamei A, et al.: Influence of viral load and genotype in the progression of hepatitis B-associated liver cirrhosis to hepatocellular carcinoma. Liver Int 2005, 25:220–225.PubMedCrossRefGoogle Scholar
  46. 46.
    Kao JH: Hepatitis B virus genotypes and hepatocellular carcinoma in Taiwan. Intervirology 2003, 46:400–407.PubMedCrossRefGoogle Scholar
  47. 47.
    Sezaki H, Kobayashi M, Hosaka T, et al.: Hepatocellular carcinoma in noncirrhotic young adult patients with chronic hepatitis B viral infection. J Gastroenterol 2004, 39:550–556.PubMedCrossRefGoogle Scholar
  48. 48.
    Sugauchi F, Orito E, Ichida T, et al.: Epidemiologic and virologic characteristics of hepatitis B virus genotype B having the recombination with genotype C. Gastroenterology 2003, 124:925–932.PubMedCrossRefGoogle Scholar
  49. 49.
    Kao JH, Chen DS: Clinical relevance of hepatitis B virus genotypes Ba and Bj in Taiwan. Gastroenterology 2003, 125:1916–1917.PubMedCrossRefGoogle Scholar
  50. 50.
    Thakur V, Guptan RC, Kazim SN, et al.: Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent. J Gastroenterol Hepatol 2002, 17:165–170.PubMedCrossRefGoogle Scholar
  51. 51.
    Kobayashi M, Suzuki F, Akuta N, et al.: Virological differences between patients infected with subtypes Ba and Bj of hepatitis B virus genotype B. J Gastroenterol Hepatol 2005, 20:570–576.PubMedCrossRefGoogle Scholar
  52. 52.
    Sugauchi F, Kumada H, Acharya SA, et al.: Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A. J Gen Virol 2004, 85:811–820.PubMedCrossRefGoogle Scholar
  53. 53.
    Kramvis A, Kew MC, Bukofzer S: Hepatitis B virus precore mutants in serum and liver of Southern African Blacks with hepatocellular carcinoma. J Hepatol 1998, 28:132–141.PubMedCrossRefGoogle Scholar
  54. 54.
    Tanaka Y, Hasegawa I, Kato T, et al.: A case-control study for differences among hepatitis B virus infections of genotypes A (subtypes Aa and Ae) and D. Hepatology 2004, 40:747–755.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  1. 1.College of Medicine, National Taiwan UniversityTaipeiTaiwan

Personalised recommendations