Skip to main content

Advertisement

SpringerLink
Log in

Coexistence of hepatitis B surface antigen and anti-HBs in Chinese chronic hepatitis B virus patients relating to genotype C and mutations in the S and P gene reverse transcriptase region

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

We aimed to determine the prevalence of the coexistence of HBsAg and anti-HBs and to analyze the clinical and virological features of infection, including amino acid (aa) patterns of the S gene and reverse transcriptase (RT) region in Chinese chronic hepatitis B (CHB) patients. Fifty-four (2.90%) CHB patients who were positive for both HBsAg and anti-HBs were tested, and sequences were obtained from 52 of them as well as 48 patients from a control group. S gene and RT region sequences were amplified and sequenced using in-house protocols. There was no significant difference between patients with and without anti-HBs with regard to age, gender, alanine aminotransferase level, and the proportion positive for HBeAg and HBcAb. The occurrence of genotype C (P = 0.001) and anti-HBeAb positivity (P = 0.027) was significantly higher in HBsAg+/anti-HBs+ individuals. In the S gene, the number of mutated residues in the HBsAg+/anti-HBs+ group was markedly higher than in control patients (1.88 versus 1.02 substitutions per 100 amino acids, P = 0.022). The amino acid exchange occurred mostly within the N-terminal region (2.15 versus 0.87 substitutions per 100 amino acids, P = 0.023) and the “a” determinant (3.61 versus 1.56 substitutions per 100 amino acids, P = 0.049) in the two groups. In the RT region, the mean number of substitution per 100 aa showed a tendency to be significantly higher in HBsAg+/anti-HBs+ patients than in controls (2.34 versus 1.46, P = 0.040). This study showed a prevalence of coexistence of anti-HBs in HBsAg-positive patients and an increased frequency of genotype C and aa variability within both HBsAg and RT involving functionally important regions of those proteins.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

HBV:

Hepatitis B virus

HBsAg:

Hepatitis B surface antigen

CHB:

Chronic hepatitis B

ALT:

Alanine aminotransferase

References

  1. Fattovich G, Brollo L, Giustina G, Noventa F, Pontisso P, Alberti A, Realdi G, Ruol A (1991) Natural history and prognostic factors for chronic hepatitis type B. Gut 32:294–298

    Article  PubMed  CAS  Google Scholar 

  2. Liaw YF, Tai DI, Chu CM, Chen TJ (1988) The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 8:493–496

    Article  PubMed  CAS  Google Scholar 

  3. Beasley RP, Hwang LY, Lin CC, Chien CS (1981) Hepatocellular carcinoma and hepatitis B virus: a prospective study of 22 707 men in Taiwan. Lancet 2:1129–1133

    Article  PubMed  CAS  Google Scholar 

  4. Yang R, Cong X, Xu Z, Xu D, Huang W, Maertens R, Wei L (2010) INNO-LiPA HBV genotyping is highly consistent with direct sequencing and sensitive in detecting B/C mixed genotype infection in Chinese chronic hepatitis B patients and asymptomatic HBV carriers. Clin Chim Acta 411:1951–1956

    Article  PubMed  CAS  Google Scholar 

  5. Lada O, Benhamou Y, Poynard T, Thibault V (2006) Coexistence of hepatitis B surface antigen (HBs Ag) and anti-HBs antibodies in chronic hepatitis B virus carriers: influence of “a” determinant variants. J Virol 80:2968–2975

    Article  PubMed  CAS  Google Scholar 

  6. Zhang JM, Xu Y, Wang XY, Yin YK, Wu XH, Weng XH, Lu M (2007) Coexistence of hepatitis B surface antigen (HBsAg) and heterologous subtype-specific antibodies to HBsAg among patients with chronic hepatitis B virus infection. Clin Infect Dis 44:1161–1169

    Article  PubMed  CAS  Google Scholar 

  7. Colson P, Borentain P, Motte A, Henry M, Moal V, Botta-Fridlund D, Tamalet C, Gerolami R (2007) Clinical and virological significance of the co-existence of HBsAg and anti-HBs antibodies in hepatitis B chronic carriers. Virology 367:30–40

    Article  PubMed  CAS  Google Scholar 

  8. Huang X, Qin Y, Zhang P, Tang G, Shi Q, Xu J, Qi F, Shen Q (2010) PreS deletion mutations of hepatitis B virus in chronically infected patients with simultaneous seropositivity for hepatitis-B surface antigen and anti-HBS antibodies. J Med Virol 82:23–31

    Article  PubMed  CAS  Google Scholar 

  9. Zheng X, Weinberger KM, Gehrke R, Isogawa M, Hilken G, Kemper T, Xu Y, Yang D, Jilg W, Roggendorf M, Lu M (2004) Mutant hepatitis B virus surface antigens (HBsAg) are immunogenic but may have a changed specificity. Virology 329:454–464

    PubMed  CAS  Google Scholar 

  10. Yukimasa N, Ohkushi H, Fukasawa K, Fukuchi K, Takagi Y, Gomi K (2000) Hepatitis B virus gene mutations in the sera of three patients with coexisting hepatitis B surface antigen and anti-surface antibody. Rinsho Byori 48:184–188

    PubMed  CAS  Google Scholar 

  11. Weber B (2005) Genetic variability of the S gene of hepatitis B virus: clinical and diagnostic impact. J Clin Virol 32:102–112

    Article  PubMed  CAS  Google Scholar 

  12. Wang YM, Ng WC, Lo SK (1999) Detection of pre-S/S gene mutants in chronic hepatitis B carriers with concurrent hepatitis B surface antibody and hepatitis B surface antigen. J Gastroenterol 34:600–606

    Article  PubMed  CAS  Google Scholar 

  13. Shiels MT, Taswell HF, Czaja AJ, Nelson C, Swenke P (1987) Frequency and significance of concurrent hepatitis B surface antigen and antibody in acute and chronic hepatitis B. Gastroenterology 93:675–680

    PubMed  CAS  Google Scholar 

  14. Konopnicki D, Mocroft A, de Wit S, Antunes F, Ledergerber B, Katlama C, Zilmer K, Vella S, Kirk O, Lundgren JD (2005) Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort. AIDS 19:593–601

    Article  PubMed  Google Scholar 

  15. Kao JH, Chen PJ, Lai MY, Chen DS (2000) Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 118:554–559

    Article  PubMed  CAS  Google Scholar 

  16. Carman WF (1997) The clinical significance of surface antigen variants of hepatitis B virus. J Viral Hepat 4(Suppl 1):11–20

    Article  PubMed  Google Scholar 

  17. Suwannakarn K, Tangkijvanich P, Thawornsuk N, Theamboonlers A, Tharmaphornpilas P, Yoocharoen P, Chongsrisawat V, Poovorawan Y (2008) Molecular epidemiological study of hepatitis B virus in Thailand based on the analysis of pre-S and S genes. Hepatol Res 38:244–251

    Article  PubMed  CAS  Google Scholar 

  18. Lu M, Lorentz T (2003) De novo infection in a renal transplant recipient caused by novel mutants of hepatitis B virus despite the presence of protective anti-hepatitis B surface antibody. J Infect Dis 187:1323–1326

    Article  PubMed  Google Scholar 

  19. Cooreman MP, Leroux-Roels G, Paulij WP (2001) Vaccine- and hepatitis B immune globulin-induced escape mutations of hepatitis B virus surface antigen. J Biomed Sci 8:237–247

    Article  PubMed  CAS  Google Scholar 

  20. Coleman PF (2006) Detecting hepatitis B surface antigen mutants. Emerg Infect Dis 12:198–203

    Article  PubMed  CAS  Google Scholar 

  21. Chen CH, Hung CH, Lee CM, Hu TH, Wang JH, Wang JC, Lu SN, Changchien CS (2007) Pre-S deletion and complex mutations of hepatitis B virus related to advanced liver disease in HBeAg-negative patients. Gastroenterology 133:1466–1474

    Article  PubMed  CAS  Google Scholar 

  22. Choi MS, Kim DY, Lee DH, Lee JH, Koh KC, Paik SW, Rhee JC, Yoo BC (2007) Clinical significance of pre-S mutations in patients with genotype C hepatitis B virus infection. J Viral Hepat 14:161–168

    Article  PubMed  CAS  Google Scholar 

  23. Sugauchi F, Ohno T, Orito E, Sakugawa H, Ichida T, Komatsu M, Kuramitsu T, Ueda R, Miyakawa Y, Mizokami M (2003) Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease. J Med Virol 70:537–544

    Article  PubMed  CAS  Google Scholar 

  24. Lin CL, Liu CH, Chen W, Huang WL, Chen PJ, Lai MY, Chen DS, Kao JH (2007) Association of pre-S deletion mutant of hepatitis B virus with risk of hepatocellular carcinoma. J Gastroenterol Hepatol 22:1098–1103

    Article  PubMed  CAS  Google Scholar 

  25. Shi ZJ, Yang YB, Ma L, Li XM, Schreiber A (2010) Lamivudine in late pregnancy to interrupt in utero transmission of hepatitis B virus: a systematic review and meta-analysis. Obstet Gynecol 116:147–159

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by a grant from the Shanghai Medical Key Discipline.

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, China

    Weiwei Liu, Tingting Hu, Yuming Chen, Minying Huang, Chao Yuan & Ming Guan

  2. Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Xinyu Wang

  3. Central Laboratory, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Ming Guan

Authors
  1. Weiwei Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tingting Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xinyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuming Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Minying Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chao Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ming Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ming Guan.

Additional information

W. Liu and T. Hu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, W., Hu, T., Wang, X. et al. Coexistence of hepatitis B surface antigen and anti-HBs in Chinese chronic hepatitis B virus patients relating to genotype C and mutations in the S and P gene reverse transcriptase region. Arch Virol 157, 627–634 (2012). https://doi.org/10.1007/s00705-011-1215-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-011-1215-5

Keywords

Search

Navigation