Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Hepatitis B virus genotype: What should the clinician know?


Eight genotypes (A-H) of hepatitis B virus (HBV) have been identified. The epidemiology of HBV genotypes and their implications for the natural history of disease progression and response to antiviral therapy have become increasingly recognized. This article presents new lines of evidence regarding the clinical relevance of HBV genotypes and proposes important issues to be resolved in the future.

This is a preview of subscription content, log in to check access.

References and Recommended Reading

  1. 1.

    Kao JH, Chen DS:Global control of hepatitis B virus.Lancet Infect Dis 2002,2:395–403.

  2. 2.

    Fung SK, Lok ASF:Hepatitis B virus genotypes: Do they play a role in the outcome of HBV infection? Hepatology 2004,40:790–792.

  3. 3.

    Liu CJ, Kao JH, Chen DS:Therapeutic implications of hepatitis B virus genotypes.Liver Int 2005,25:1097–1107.

  4. 4.

    Kao JH, Chen DS:HBV genotypes: epidemiology and implications regarding natural history [review].Curr Hepatitis Rep 2006,5:5–13.

  5. 5.

    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 1988,69:2575–2583.

  6. 6.

    Norder H, Courouce AM, Magnius LO:Complete genomes, phylogenetic relatedness, and structural proteins of six strains of the hepatitis B virus, four of which represent two new genotypes.Virology 1994,198:489–503.

  7. 7.

    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.

  8. 8.

    Sugauchi F, Orito E, Ichida T, et al.:Hepatitis B virus of genotype B with or without recombination with genotype C over the precore region plus the core gene.J Virol 2002,76:5985–5992.

  9. 9.

    Kramvis A, Weitzmann L, Owiredu WK, Kew MC:Analysis of the complete genome of subgroup A′, hepatitis B virus isolates from South Africa.J Gen Virol 2002,83:835–839.

  10. 10.

    Chan HL, Tsui SK, Tse CH, et al.:Epidemiological and virological characteristics of 2 subgroups of hepatitis B virus genotype C.J Infect Dis 2005,191:2022–2032.

  11. 11.

    Liu CJ, Kao JH:Subgenotypes of hepatitis B virus genotype C in Taiwan.J Infect Dis 2005,192:1308–1309.

  12. 12.

    Liu CJ, Chen BF, Chen PJ, et al.:Role of hepatitis B viral load and basal core promoter mutation in hepatocellular carcinoma in hepatitis B carriers.J Infect Dis 2006,193:1258–1265.

  13. 13.

    Yang HI, Chen PJ, Yeh SH, et al.:Risk of hepatocellular carcinoma associated with genotypes and mutants of hepatitis B virus: a community-based prospective cohort study.J Hepatol 2006,44(suppl 2):27A.

  14. 14.

    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.

  15. 15.

    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.

  16. 16.

    Orito E, Ichida T, Sakugawa H, et al.:Geographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan.Hepatology 2001,34:590–594.

  17. 17.

    Ding X, Mizokami M, Yao G, et al.:Hepatitis B virus genotype distribution among chronic hepatitis B virus carriers in Shanghai, China.Intervirology 2001,44:43–47.

  18. 18.

    Chu CM, Liaw YF:Genotype C hepatitis B virus infection is associated with a 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 at baseline.J Hepatol 2005,43:411–417.

  19. 19.

    Kao JH, Chen PJ, Lai MY, Chen DS:Acute exacerbations of chronic hepatitis B are rarely associated with superinfection of hepatitis B virus.Hepatology 2001,34:817–823.

  20. 20.

    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.

  21. 21.

    Chen CH, Lee CM, Lu SN, et al.:Clinical significance of hepatitis B virus (HBV) genotypes and precore and core promoter mutations affecting HBV e antigen expression in Taiwan.J Clin Microbiol 2005,43:6000–6006.

  22. 22.

    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.

  23. 23.

    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.

  24. 24.

    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.

  25. 25.

    Rodriguez-Frias F, Jardi R, Buti M, et al.:Hepatitis B virus genotypes and G1896A precore mutation in 486 Spanish patients with acute and chronic HBV infection.J Viral Hepat 2006,13:343–350.

  26. 26.

    Wai CT, Fontana RJ, Polson J, et al.:Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States.J Viral Hepat 2005,12:192–198.

  27. 27.

    Ozasa A, Tanaka Y, Orito E, et al.:Influence of genotypes and precore mutations on fulminant or chronic outcome of acute hepatitis B virus infection.Hepatology 2006,44:326–334.

  28. 28.

    Liaw YF, Leung N, Guan R, et al.:Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update.Liver Int 2005,25:472–489.

  29. 29.

    Kao JH, Wu NH, Chen PJ, et al.:Hepatitis B genotypes and the response to interferon therapy.J Hepatol 2000,33:998–1002.

  30. 30.

    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 2002,36:1425–1430.

  31. 31.

    Liu CJ, Lai MY, Chao YC, et al.:Interferon alpha-2b with and without ribavirin in the treatment of hepatitis B e antigen-positive chronic hepatitis B: a randomized study.Hepatology 2006,43:742–749.

  32. 32.

    Hou J, Schilling R, Janssen HL:Molecular characteristics of hepatitis B virus genotype A confer a higher response to interferon treatment.J Hepatol 2001,34(suppl 1):15.

  33. 33.

    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 2005,54:1009–1013.

  34. 34.

    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.

  35. 35.

    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 randomized trial.Lancet 2005,365:123–129.

  36. 36.

    Flink HJ, Zonneveld M, Hansen BE, et al.:Treatment with peg-interferon alfa-2b for HBeAg-positive chronic hepatitis B: HBsAg loss is associated with HBV genotype.Am J Gastroenterol 2006,101:297–303.

  37. 37.

    Cooksley G, Manns M, Lau GKK, et al.:Effect of genotype and other baseline factors on response to peginterferon alfa-2a (40KD) (Pegasys) in HBeAg-positive chronic hepatitis B: results from a large, randomized study.J Hepatol 2005,42(suppl 2):30.

  38. 38.

    Hadziyannis S, Lau GKK, Marcellin P, et al.:Sustained HBsAg seroconversion in patients with chronic hepatitis B treated with peginterferon alfa-2a (40 kDa) (Pegasys).J Hepatol 2005,42(suppl 2):178.

  39. 39.

    Kao JH, Liu CJ, Chen DS:Hepatitis B viral genotypes and lamivudine resistance [letter].J Hepatol 2002,36:303–304.

  40. 40.

    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.

  41. 41.

    Chan HL, Wong ML, Hui AY, et al.:Hepatitis B virus genotype has no impact on hepatitis B e antigen seroconversion after lamivudine treatment.World J Gastroenterol 2003,9:2695–2697.

  42. 42.

    Buti M, Cotrina M, Valdes A, et al.:Is hepatitis B virus subtype testing useful in predicting virological response and resistance to lamivudine? J Hepatol 2002,36:445–446.

  43. 43.

    Chien RN, Yeh CT, Tsai SL, et al.:Determinants for sustained HBeAg response to lamivudine therapy.Hepatology 2003,38:1267–1273.

  44. 44.

    Zollner B, Petersen J, Schroter M, et al.:20-fold increase in risk of lamivudine resistance in hepatitis B virus subtype adw.Lancet 2001,357:934–935.

  45. 45.

    Zollner B, Petersen J, Puchhammer-Stockl E, et al.:Viral features of lamivudine resistant hepatitis B genotypes A and D.Hepatology 2004,39:42–50.

  46. 46.

    Akuta N, Suzuki F, Kobayashi M, et al.:The influence of hepatitis B virus genotype on the development of lamivudine resistance during long-term treatment.J Hepatol 2003,38:315–321.

  47. 47.

    Orito E, Fujiwara K, Tanaka Y, et al.:A case-control study of response to lamivudine therapy for 2 years in Japanese and Chinese patients chronically infected with hepatitis B virus of genotypes Bj, Ba and C.Hepatol Res 2006,35:127–134.

  48. 48.

    Westland C, Delaney W 4th, 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.

  49. 49.

    Fung SK, Chae HB, Fontana RJ, et al.:Virologic response and resistance to adefovir in patients with chronic hepatitis B.J Hepatol 2006,44:283–290.

  50. 50.

    Lurie Y, Manns MP, Gish RG, et al.:The efficacy of entecavir is similar regardless of disease-related baseline subgroups in treatment of nucleoside-naïve HBeAg(+) and HBeAg(−) patients with chronic hepatitis B.J Hepatol 2005,42(suppl 2):184.

  51. 51.

    Liu CJ, Kao JH, Chen DS:Mixed hepatitis B virus genotype infections: the more, the worse? [letter].Hepatology 2006,44:770.

  52. 52.

    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.

  53. 53.

    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.

  54. 54.

    Chen BF, Liu CJ, Jow GM, et al.:Evolution of hepatitis B virus in an acute hepatitis B patient co-infected with genotypes B and C.J Gen Virol 2006,87:39–49.

  55. 55.

    Toan NL, Song LH, Kremsner PG, et al.:Impact of the hepatitis B virus genotype and genotype mixtures on the course of liver disease in Vietnam.Hepatology 2006,43:1375–1384.

  56. 56.

    Liu CJ, Chen PJ, Wang HY, et al.:Lack of interferon sensitivity-determining region in the genome of hepatitis B virus genotype Ba.Antivir Ther 2004,9:895–903.

  57. 57.

    Jazayeri MS, Basuni AA, Cooksley G, et al.:Hepatitis B virus genotypes, core gene variability and ethnicity in the Pacific region.J Hepatol 2004,41:139–146.

  58. 58.

    Lin CL, Kao JH, Chen BF, et al.:Application of hepatitis B virus genotyping and phylogenetic analysis in intrafamilial transmission of hepatitis B virus.Clin Infect Dis 2005,41:1576–1581.

  59. 59.

    Lobato C, Tavares-Neto J, Rios-Leite M, et al.:Intrafamilial prevalence of hepatitis B virus in Western Brazilian Amazon region: epidemiologic and biomolecular study.J Gastroenterol Hepatol 2006,21:863–868.

  60. 60.

    Keeffe EB, Dieterich DT, Han SB, et al.:A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: an update.Clin Gastroenterol Hepatol 2006,4:936–962.

Download references

Author information

Correspondence to Jia-Horng Kao MD, PhD.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Liu, C., Kao, J. Hepatitis B virus genotype: What should the clinician know?. Current Hepatitis Reports 6, 17–23 (2007).

Download citation


  • Lamivudine
  • Entecavir
  • HBeAg Seroconversion
  • Adefovir Dipivoxil
  • Basal Core Promoter