Intervirology 2001;44:43–47

Hepatitis B Virus Genotype Distribution among Chronic Hepatitis B Virus Carriers in Shanghai, China

Ding X.a,b · Mizokami M.a · Yao G.c · Xu B.c · Orito E.a · Ueda R.a · Nakanishi M.b
aSecond Department of Medicine, bSecond Department of Biochemistry, Nagoya City University School, Nagoya, Japan; cClinical Immunology Research Center, Shanghai Jing An Qu Center Hospital, Shanghai, China
email Corresponding Author

 goto top of outline Key Words

  • Hepatitis B virus
  • Genotypes
  • Restriction fragment length polymorphism
  • Shanghai
  • China

 goto top of outline Abstract

Objective: Hepatitis B virus (HBV) genotype distribution is still unclear in China, where a high prevalence of HBV infection exists, although it is well known that HBV can be classified into six genotypes based on intergroup divergence. The aim of this study was to investigate the epidemiological distribution of HBV genotypes and to clarify further the genotype-related differences in the pathogenicity of HBV. Methods: Seminested PCR and restriction fragment length polymorphism analysis were conducted in 97 asymptomatic HBV carriers (ASC) and 46 chronic hepatitis (CH), 37 liver cirrhosis (LC) and 44 hepatocellular carcinoma (HCC) patients in Shanghai, China. Results: Two hundred and twenty samples (98.2%) were positive for HBV DNA, and of these, 3 (1.4%), 38 (17.2%) and 179 (81.4%) were classified as genotype A, B and C, respectively. There was a statistically significant difference in the distribution of genotypes B and C among various categories of liver diseases (p < 0.01). The distribution of genotype C showed an increasing trend from ASC, CH and LC to the HCC group; in contrast, the distribution of genotype B showed a decreasing trend in the same order. HBeAg positivity was higher in genotype C than in genotype B in all the subjects or in the ASC group alone (p < 0.05, p < 0.01, respectively). More severe liver damage and a higher mean age were observed in genotype C than in genotype B (p < 0.01, p < 0.05, respectively). Conclusions: These results indicate the following: (1) genotypes A, B and C of HBV exist in Shanghai, China; (2) genotype C is the major genotype in this area; (3) genotype C is associated with the development of severe liver diseases, and (4) genotype B has a relatively good prognosis.

Copyright © 2001 S. Karger AG, Basel

 goto top of outline References
  1. Yao JL: Perinatal transmission of hepatitis B virus infection and vaccination in China. Gut 1996;2:S37–S38.
  2. Zhang JY, Wang X, Han SG, Zhuang H: A case-control study of risk factors for hepatocellular carcinoma in Henan, China. Am J Trop Med Hyg 1998;59:947–951.

    External Resources

  3. Cong W, Wu M, Wang Y: Clinicopathological study on 3,160 cases of liver tumors (in Chinese). Chung Hua Ping Li Hsueh Tsa Chih 1997;26:70–73.
  4. Seiji K, Inoue O, Watanabe M, Takahashi S, Chen Z, Huang MY, Cai SX, Nakatsuka H, Watanabe T, Ikeda M: Hepatitis B virus prevalence in industrialized cities in China. Asia Pac J Public Health 1991;5:350–358.
  5. Zhou YZ, Butel JS, Li PJ, Finegold MJ, Melnick JL: Integrated state of subgenomic fragments of hepatitis B virus DNA in hepatocellular carcinoma from mainland China. J Natl Cancer Inst 1987;79:223–231.

    External Resources

  6. Zhou XD, DeTolla L, Custer RP, London WT: Iron, ferritin, hepatitis B surface and core antigens in the livers of Chinese patients with hepatocellular carcinoma. Cancer 1987;59:1430–1437.
  7. Mizokami M, Nakano T, Orito E, Tanaka Y, Sakugawa H, Mukaide M, Robertson BH: Hepatitis B virus genotype assignment using restriction fragment length polymorphism patterns. FEBS Lett 1999;450:66–71.

    External Resources

  8. Okamoto H, Tsuda F, Sakugawa H, Sastrosoewignjo RI, Imai M, Miiyakawa Y, Mayumi M: Typing hepatitis B virus by homology in nucleotide sequence: Comparison of surface antigen subtypes. J Gen Virol 1988;69:2575–2583.
  9. 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.
  10. Courouce-Pauty AM, Lemaire JM, Roux JF: New hepatitis B surface antigen subtypes inside the ad category. Vox Sang 1978;35:304–308.

    External Resources

  11. Nishioka K, Levin AG, Simons MJ: Hepatitis B antigen, antigen subtypes, and hepatitis B antibody in normal subjects and patients with liver disease. Bull World Health Organ 1975;52:293–300.

    External Resources

  12. Sung JL, Chen DS: Geographical distribution of the subtype of hepatitis B surface antigen in Chinese. Gastroenterol Jpn 1977;12:58–63.
  13. Fan J, Zhuang H, Li Y: Comparison of sequences of hepatitis B virus S gene fragment in eight cities of China (in Chinese). Chung Hua Yu Fang I Hsueh Tsa Chih 1997;31:140–143.
  14. Norder H, Hammas B, Lee SD, Bile K, Courouce AM, Mushahwar IK, Magnius LO: Genetic relatedness of hepatitis B viral strains of diverse geographical origin and natural variations in the primary structure of the surface antigen. J Gen Virol 1993;74:1341–1348.
  15. Lindh M, Andersson AS, Gusdal A: Genotypes, nt 1858 variants, and geographic origin of hepatitis B virus – large-scale analysis using a new genotyping method. J Infect Dis 1997;175:1285–1293.
  16. Li JS, Tong SP, Wen YM, Vitvitski L, Zhang Q, Trepo C: 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;67:5402–5410.
  17. Telenta PF, Poggio GP, Lopez JL, Gonzalez J, Lemberg A, Campos RH: Increased prevalence of genotype F hepatitis B virus isolates in Buenos Aires, Argentina. J Clin Microbiol 1997;35:1873–1875.

    External Resources

  18. Arauz-Ruiz P, Norder H, Visona KA, Magnius LO: Genotype F prevails in HBV infected patients of hispanic origin in Central America and may carry the precore stop mutant. J Med Virol 1997;51:305–312.
  19. Naumann H, Schaefer S, Yoshida CF, Gaspar AM, Repp R, Gerlich WH: Identification of a new hepatitis B virus (HBV) genotype from Brazil that expresses HBV surface antigen subtype adw4. J Gen Virol 1993;74:1627–1632.
  20. Sastrosoewignjo RI, Sandjaja B, Okamoto H: Molecular epidemiology of hepatitis B virus in Indonesia. J Gastroenterol Hepatol 1991;6:491–498.
  21. 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.
  22. Sakugawa H, Ohwan T, Yamashiro A, Oyakawa T, Keneda K, Kinjo F, Saito A: Natural seroconversion from hepatitis Be antigen to antibody among hepatitis B virus carriers in Okinawa Islands. J Med Virol 1991;34:122–126.
  23. Shiina S, Fujino H, Kawabe T, Tagawa K, Unuma T, Yoneyama M, Ohmori T, Suzuki S, Kurita M, Ohashi Y: Relationship of HBsAg subtypes with HBeAg/anti-HBe status and chronic liver diseases. Am J Gastroenterol 1991;86:872–875.
  24. Hoofnagle JH, Dusheiko GM, Seeff LB, Jones EA, Waggoner JG, Bales ZB: Seroconversion from hepatitis Be antigen to antibody in chronic type B hepatitis. Ann Intern Med 1981;94:744–748.
  25. Lindh M, Hannoun C, Dhillon AP, Norkrans G, Horal P: Core promoter mutations and genotypes in relation to viral replication and liver damage in East Asian hepatitis B virus carriers. J Infect Dis 1999;179:775–782.

 goto top of outline Author Contacts

Masashi Mizokami, MD, PhD
Second Department of Medicine, Nagoya City University Medical School
Kawasumi, Mizuho, Nagoya 467-8601 (Japan)
Tel. +81 52 853 8681, Fax +81 52 853 8682

 goto top of outline Article Information

Received: Received: October 2, 2000
Accepted: November 3, 2000
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 3, Number of References : 25

 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)
Founded 1973 by J.L. Melnick; continued by F. Rapp (1986–1990); M.J. Buchmeier and C.R. Howard (1991–1993)

Vol. 44, No. 1, Year 2001 (Cover Date: January-February 2001)

Journal Editor: Rüdiger W. Braun, Stuttgart
ISSN: 0300–5526 (print), 1423–0100 (Online)

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