Skip to main content
Log in

Prevalence of Hepatitis B Virus Genotype D in Precore Mutants Among Chronic Liver Disease Patients from New Delhi, India

  • ORIGINAL ARTICLE
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Hepatitis B is one of the most important causes of chronic viral hepatitis world wide. Mutations in the precore region of the hepatitis B virus (HBV) genome are frequently found in hepatitis B envelope antigen-negative cases. Data from India on the HBV genotype-associated distribution of precore mutations are limited. Our objective in this study was to genotype and detect the precore mutant with a point mutation from G to A at nucleotide 1896 using ligase chain reaction (LCR) and direct sequencing. A total of 115 cases of chronic liver disease were screened. The cases were evaluated on the basis of history, clinical examination, liver function profile, and serological test for HBV infection, which includes HBsAg, anti HBcIgG, HBeAg using commercially available ELISA kits. The cases, which were HBeAg+, HBeAg–, and HBV DNA+, were subjected to LCR and confirmed by direct sequencing. Of 115 chronic liver disease cases, 50 (43.5%) cases were HBV DNA positive. All cases were subjected to LCR; 11 (22%) cases confirmed the presence of precore mutants, while the remaining 39 (78%) were classified as the wild form of the virus. HBV genotyping by direct sequencing revealed that genotype D was predominant in both wild and mutant forms of the virus. We conclude that the HBV genotype distribution was not significantly different between precore mutants and the wild form of the virus (P>0.05). North Indian patients with genotype D were more likely to have persistent HBV infection with precore mutants. HBV genotypes correlate with the clinical outcome of chronic HBV infection.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Purcel RH (1993) The discovery of the hepatitis viruses. Gastroenterology 104:955–963

    Google Scholar 

  2. Kumar A, Kumar SI, Pandey R, Naik S, Aggarwal R (2005) Hepatitis B virus genotype A is more often associated with severe liver disease in northern India than is genotype D. Indian J Gastroenterol 24:19–22

    PubMed  Google Scholar 

  3. Chu CJ, Lok AS (2002) Clinical significance of hepatitis B virus genotypes. Hepatology 35:1274–1276

    Article  PubMed  Google Scholar 

  4. Arauz-Ruiz P, Norder H, Robertson BH, Magnius LO (2002) GenotypeH: a new Amerindian genotype of hepatitis B virus reveled in Central America. J Gen Virol 83:2059–2073

    PubMed  CAS  Google Scholar 

  5. Blackberg J, Kidd-Ljunggren K (2003) Mutations within the hepatitis B virus genome among chronic hepatitis B patients with hepatocellular carcinoma. J Med Virol 71(1):18–23

    Google Scholar 

  6. Yuen MF, Sablon E, Wong DK, Yuan HJ, Wong BC, Chan AO, Lai CL (2003) Role of hepatitis B virus genotypes in chronic hepatitis B exacerbation. Clin Infect Dis 37(4):593–597

    Google Scholar 

  7. Chu CJ, Keeffe EB, Han SH, et al. (2003) Hepatitis B virus genotypes in the United States of a nation wide study. Gastroenterology 125:444–451

    Article  PubMed  Google Scholar 

  8. Carman WF, Ferrao M, LOK ASF, Ma OCK, Lai CL, Thomas HC (1992) Precore sequence variation in Chinese isolates of Hepatitis B virus. J Infect Dis 165:127–133

    PubMed  CAS  Google Scholar 

  9. Brunetto MR, Stemler M, Schodel F, et al. (1989) Identification of HBV variant which cannot produce precore derived HBeAg and may be responsible for severe hepatitis. Ital J Gastroenterol Hepatol 21:151–154

    Google Scholar 

  10. Carman WF, Jacyna MR, Hadziyannis S, et al. (1989) Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet 2:588–591

    Article  PubMed  CAS  Google Scholar 

  11. Baumert TF, Marrone A, Vergalla J, Liang TJ (1998) Naturally occurring mutations define a novel function of the hepatitis B virus core promoter in core protein expression. J Virol 72(8):6785–6795

    Google Scholar 

  12. Kramvis A, Kew MC (1998) Structure and function of the encapsidation signal of hepadnaviridae. J Viral Hepat 5(6):357–367

    Google Scholar 

  13. Kosaka Y, Takase K, Kojima M, et al. (1991) Fuminant hepatitis B: induction by hepatitis B virus mutants defective in the precore region and core capable of encoding e antigen. Gastroenterology 100:1087–1094

    PubMed  CAS  Google Scholar 

  14. Barany F (1991) Genetic disease detection and DNA amplification using cloned thermostable ligase. Proc Natl Acad Sci USA 88(1):189–193

    Google Scholar 

  15. McMahon BJ, Bulkow L, Harpster A, et al. (2000) Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology 32:842–846

    Article  PubMed  CAS  Google Scholar 

  16. Yuen MF, Cheng CC, Lauder IJ, et al. (2000) Early detection of hepatocellular carcinoma increases the chance of treatment—Hong Kong experience. Hepatology 31:330–335

    Article  PubMed  CAS  Google Scholar 

  17. Lee WM (1997) Hepatitis B virus infection. N Engl J Med 337(24):1733–1745

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  19. Wai CT, Chu CJ, Hussain M, et al. (2002) HBV genotype B is associated with better response to interferon therapy in HBeAg-positive chronic hepatitis than genotype C. Hepatology 36:1425–1430

    Article  PubMed  CAS  Google Scholar 

  20. Erhardt A, Reineke U, Blondin D, et al. (2000) Mutations of the core promoter and response to interferon treatment in chronic replicative hepatitis B. Hepatology 31:716–725

    Article  PubMed  CAS  Google Scholar 

  21. Orito E, Mizokimi M, Sakugawa H, et al. (2001) A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C. Japan HBV Genotypes Research Groups. Hepatology 33:218–223

    Article  PubMed  CAS  Google Scholar 

  22. Ding X, Mizokami M, Yao G, Xu B, Ueda R (2001) Hepatitis virus genotype distribution among chronic hepatitis B virus carriers in Shanghai. China. Int Virol 44:43–47

    CAS  Google Scholar 

  23. Thakur V, Rehman S, Guptan RC, Kazim SN, Kumar S, Sarin SK (2002) Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian Subcontinent. J Gastroenterol Hepatol 17(2):113–115

    Article  Google Scholar 

  24. Gandhe SS, Chadha MS, Arankalle VA (2003) Hepatitis B virus genotype and serotypes in western India: lack of clinical significance. J Med Virol 69(3):324–330

    Article  PubMed  CAS  Google Scholar 

  25. Grandjacques C, Pradat P, Stuyver L, et al. (2000) Rapid detection of genotypes and mutations in the precore promoter and the pre-core region of hepatitis B virus genome: correlation with viral persistence and disease severity. J Hepatol 33:430–439

    Article  PubMed  CAS  Google Scholar 

  26. Lok ASF, Akarca U, Greene S (1994) Mutation in the pre-core region of hepatitis B virus severe to enhance the stability of the secondary structure of the pre-genome encapsidation signal. Proc. Natl Acad Sci USA 91:4077–4081

    Article  Google Scholar 

  27. Mangia A, Chung YH, Hoofnagle JH, Birkenmeyer L, Mushahwar I, Di Bisceglie Am (1996) Pathogenesis of chronic liver disease in patients with chronic hepatitis B virus infection without serum HBeAg. Dig Dis Sci 41:2447–2452

    Article  PubMed  CAS  Google Scholar 

  28. Zuckerman AJ, Zuckerman JN (1999) Molecular epidemiology of hepatitis B virus mutants. J Med Virol 58:193–195

    Article  PubMed  CAS  Google Scholar 

  29. Hadziyannis SJ, Vassilopoulos D (2001) Hepatitis B e antigen-negative chronic hepatitis B. Hepatology 34:617–624

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Premashis Kar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kar, P., Polipalli, S.K., Chattopadhyay, S. et al. Prevalence of Hepatitis B Virus Genotype D in Precore Mutants Among Chronic Liver Disease Patients from New Delhi, India. Dig Dis Sci 52, 565–569 (2007). https://doi.org/10.1007/s10620-006-9625-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9625-z

Keywords

Navigation