Hepatitis B Virus Genotypes and Variants

Overview

Journal Cold Spring Harb Perspect Med

Specialty General Medicine

Date 2015 May 3

PMID 25934462

Citations 106

Authors

Chih-Lin Lin

Jia-Horng Kao

Affiliations

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Abstract

At least 10 hepatitis B virus (HBV) genotypes (A to J) with distinct geographic distributions and several HBV mutants, including precore/core promoter mutations and pre-S/S deletion mutations, have been recognized to be not only predictive of liver disease progression but also associated with response to antiviral therapy. HBV genotype-specific pathogenesis may contribute to heterogeneous clinical outcomes in chronic hepatitis B patients across the world. For example, patients with HBV genotypes C and D infection have a lower rate of spontaneous HBeAg seroconversion. In addition, HBV genotypes C and D have a higher frequency of core promoter and pre-S mutations than genotypes A and B. Genotypes C and D also carry a higher lifetime risk of cirrhosis and HCC development than genotypes A and B. Core promoter and pre-S mutations also correlate with an increased risk of hepatocellular carcinoma (HCC). Therapeutically, genotypes A and B patients have a better response to interferon-based therapy than genotypes C and D patients, but the response to nucleos(t)ide analogs is comparable across different HBV genotypes. In conclusion, HBV genotypes and variants may serve as viral genetic markers to predict disease progression as well as help practicing physicians optimize individualized antiviral therapy in clinical practice.

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References

Erhardt A, Blondin D, Hauck K, Sagir A, Kohnle T, Heintges T . Response to interferon alfa is hepatitis B virus genotype dependent: genotype A is more sensitive to interferon than genotype D. Gut. 2005; 54(7):1009-13. PMC: 1774609. DOI: 10.1136/gut.2004.060327. View

Sugiyama M, Tanaka Y, Kato T, Orito E, Ito K, Acharya S . Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigens. Hepatology. 2006; 44(4):915-24. DOI: 10.1002/hep.21345. View

Marcellin P, Bonino F, Lau G, Farci P, Yurdaydin C, Piratvisuth T . Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology. 2009; 136(7):2169-2179.e1-4. DOI: 10.1053/j.gastro.2009.03.006. View

Tatematsu K, Tanaka Y, Kurbanov F, Sugauchi F, Mano S, Maeshiro T . 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(20):10538-47. PMC: 2753143. DOI: 10.1128/JVI.00462-09. View

Suzuki Y, Kobayashi M, Ikeda K, Suzuki F, Arfase Y, Akuta N . Persistence of acute infection with hepatitis B virus genotype A and treatment in Japan. J Med Virol. 2005; 76(1):33-9. DOI: 10.1002/jmv.20320. View

LE BOUVIER G, McCOLLUM R, Hierholzer Jr W, Irwin G, Krugman S, GILES J . Subtypes of Australia antigen and hepatitis-B virus. JAMA. 1972; 222(8):928-30. DOI: 10.1001/jama.222.8.928. View

Kim H, Jee Y, Song B, Shin J, Yang S, Mun H . Molecular epidemiology of hepatitis B virus (HBV) genotypes and serotypes in patients with chronic HBV infection in Korea. Intervirology. 2006; 50(1):52-7. DOI: 10.1159/000096313. View

Kao J, Chen P, Lai M, Chen D . Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriers. J Med Virol. 2004; 72(3):363-9. DOI: 10.1002/jmv.10534. View

Buster E, Hansen B, Lau G, Piratvisuth T, Zeuzem S, Steyerberg E . Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa. Gastroenterology. 2009; 137(6):2002-9. DOI: 10.1053/j.gastro.2009.08.061. View

10.

Yuen M, Wong D, Sablon E, Tse E, Ng I, Yuan H . HBsAg seroclearance in chronic hepatitis B in the Chinese: virological, histological, and clinical aspects. Hepatology. 2004; 39(6):1694-701. DOI: 10.1002/hep.20240. View

11.

Littlejohn M, Davies J, Yuen L, Edwards R, Sozzi T, Jackson K . Molecular virology of hepatitis B virus, sub-genotype C4 in northern Australian Indigenous populations. J Med Virol. 2014; 86(4):695-706. DOI: 10.1002/jmv.23888. View

12.

Orito E, Sugauchi F, Tanaka Y, Ichida T, Sata M, Tanaka E . Differences of hepatocellular carcinoma patients with hepatitis B virus genotypes of Ba, Bj or C in Japan. Intervirology. 2005; 48(4):239-45. DOI: 10.1159/000084601. View

13.

Moucari R, Martinot-Peignoux M, Mackiewicz V, Boyer N, Ripault M, Castelnau C . Influence of genotype on hepatitis B surface antigen kinetics in hepatitis B e antigen-negative patients treated with pegylated interferon-alpha2a. Antivir Ther. 2009; 14(8):1183-8. DOI: 10.3851/IMP1458. View

14.

Kao J . Hepatitis B virus genotypes and hepatocellular carcinoma in Taiwan. Intervirology. 2003; 46(6):400-7. DOI: 10.1159/000074999. View

15.

Heijtink R, Paulij W, van Roosmalen M, Hellings J, Niesters H, Schalm S . Characteristics of the early phase of chronicity in acute hepatitis B infection. J Med Virol. 1999; 57(4):331-6. DOI: 10.1002/(sici)1096-9071(199904)57:4<331::aid-jmv1>3.0.co;2-5. View

16.

Kobayashi M, Suzuki F, Arase Y, Akuta N, Suzuki Y, Hosaka T . Infection with hepatitis B virus genotype A in Tokyo, Japan during 1976 through 2001. J Gastroenterol. 2004; 39(9):844-50. DOI: 10.1007/s00535-004-1400-3. View

17.

Roman S, Tanaka Y, Khan A, Kurbanov F, Kato H, Mizokami M . Occult hepatitis B in the genotype H-infected Nahuas and Huichol native Mexican population. J Med Virol. 2010; 82(9):1527-36. DOI: 10.1002/jmv.21846. View

18.

Kao J, Chen D . Global control of hepatitis B virus infection. Lancet Infect Dis. 2002; 2(7):395-403. DOI: 10.1016/s1473-3099(02)00315-8. View

19.

Tseng T, Liu C, Su T, Wang C, Chen C, Chen P . Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters. Gastroenterology. 2011; 141(2):517-25, 525.e1-2. DOI: 10.1053/j.gastro.2011.04.046. View

20.

Nishioka K, LEVIN A, SIMONS M . Hepatitis B antigen, antigen subtypes, and hepatitis B antibody in normal subjects and patients with liver disease. Bull World Health Organ. 1975; 52(3):293-300. PMC: 2366375. View