Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Low Frequency of Precore Mutants in Anti-Hepatitis B e Antigen Positive Subjects with Chronic Hepatitis B Virus Infection in Chennai, Southern India

  • Shanmugam, Saravanan (YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services) ;
  • Velu, Vijayakumar (Department of Microbiology, Faculty of Medicine, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras) ;
  • Nandakumar, Subhadra (Department of Microbiology, Faculty of Medicine, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras) ;
  • Madhavan, Vidya (YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services) ;
  • Shanmugasundaram, Uma (YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services) ;
  • Shankar, Esaki Muthu (YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services) ;
  • Murugavel, Kailapuri G. (YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services) ;
  • Balakrishnan, Pachamuthu (YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services) ;
  • Kumarasamy, Nagalingeswaran (YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services) ;
  • Solomon, Suniti (YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services) ;
  • Thyagarajan, Sadras Panchatcharam (YR Gaitonde Centre for AIDS Research and Education, Voluntary Health Services)
  • Published : 2008.10.31
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Abstract

The natural course of chronic hepatitis B (CH-B) virus infection is reportedly variable, and the long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B infection are distinct from HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in the south Indian setting remain largely unclear. We prospectively studied 679 consecutive patients for HBsAg, HBeAg, anti-HBe, and HBV DNA by qualitative PCR. Randomly selected samples were subjected to bidirectional sequencing to reveal core/precore variants. Of the total 679 chronic HBV cases investigated, 23% (154/679) were replicative HBV carriers. Furthermore, amongst the 560 HBV DNA samples analyzed, 26% (146/560) were viremic. Among the 154 HBeAg positive cases, HBV DNA was positive in 118 cases (77%), significantly (p<0.001) higher than the anti-HBe positive (7%) (28/406) cases. Significant increase in liver disease (p<0.01) with ALT enzyme elevation (p<0.001) was observed in both HBe and anti-HBe viremic cases. Interestingly, low frequencies of mutations were seen in the precore region of the HBV strains studied. HBV precore and core promoter variants were less often detected in subjects with "e" negative chronic HBV infection and, therefore, may not have a prognostic role in determining liver disease sequelae in this part of tropical India.

Keywords

References

  1. Acharya, S. K. 2005. Management of chronic hepatitis B: The Indian perspective. Trop. Gastroenterol. 26: 171-172
  2. Aggarwal, R., U. C. Ghoshal, and S. R. Naik. 2003. Assessment of cost effectiveness of universal hepatitis B immunization in a low income country with intermediate endemicity using a Markov model. J. Hepatol. 38: 215-222
  3. Akarca, U. S. and A. S. Lok. 1995. Naturally occurring hepatitis B virus core gene mutations. Hepatology 22: 50-60
  4. Banerjee, A., S. Banerjee, A. Chowdhury, A. Santra, S. Chowdhury, S. Roychowdhury, C. K. Panda, S. K. Bhattacharya, and R. Chakravarty. 2005. Nucleic acid sequence analysis of basal core promoter/precore/core region of hepatitis B virus isolated from chronic carriers of the virus from Kolkata, eastern India: Low frequency of mutation in the precore region. Intervirology 48: 389-399 https://doi.org/10.1159/000086066
  5. Bertoletti, A., A. Sette, F. V. Chisari, A. Penna, M. Levrero, M. De Carli, F. Fiaccadori, and C. Ferrari. 1994. Natural variants of cytotoxic epitopes are T-cell receptor antagonist for antiviral cytotoxic T-cells. Nature 369: 407-410 https://doi.org/10.1038/369407a0
  6. Chan, H. L. Y., N. W. Y. Leung, M. Hussain, M. L. Wong, and A. S. F. Lok. 2000. Hepatitis B e antigen negative chronic hepatitis B in Hong Kong. Hepatology 31: 763-768 https://doi.org/10.1002/hep.510310330
  7. Chauhan, R., S. N. Kazim, J. Bhattacharjee, P. Sakhuja, and S. K. Sarin. 2006. Basal core promoter, precore region mutations of HBV and their association with e antigen, genotype, and severity of liver disease in patients with chronic hepatitis B in India. J. Med. Virol. 78: 1047-1054 https://doi.org/10.1002/jmv.20661
  8. Chowdhury, A., A. Santra, R. Chakravorty, A. Banerji, S. Pal, G. K. Dhali, et al. 2005. Community-based epidemiology of hepatitis B virus infection in West Bengal, India: Prevalence of hepatitis B e antigen-negative infection and associated viral variants. J. Gastroenterol. Hepatol. 20: 1712-1720 https://doi.org/10.1111/j.1440-1746.2005.04070.x
  9. Chowdhury, A., A. Santra, S. Chaudhuri, A. Ghosh, P. Banerjee, and G. D. N. Mazumder. 1999. Prevalence of hepatitis B infection in the general population: A rural community based study. Trop. Gastroenterol. 20: 75-77
  10. Chuang, W. L., M. Omata, T. Ehata, O. Yokosuka, Y. Ito, F. Imazeki, S. N. Lu, W. Y. Chang, and M. Ohto. 1993. Precore mutations and core clustering mutations in chronic hepatitis B virus infection. Gasteroenterology 104: 263-271 https://doi.org/10.1016/0016-5085(93)90861-6
  11. Dumpis, U., M. Mendy, A. Hill, M. Thursz, A. Hall, H. Whittle, and P. Karayiannis. 2001. Prevalence of HBV core promoter/ precore/core mutations in Gambian chronic carriers. J. Med. Virol. 65: 664-670 https://doi.org/10.1002/jmv.2088
  12. Fagan, E. A. and T. J. Harrison. 1994. Candidate hepatitis F in sporadic non-A, non-B acute liver failure: Exclusion in liver of hepatitis viruses A, E, C, and B by polymerase chain reaction, pp. 73-76. In K. Nishioka, H. Susuki, S. Mishiro, and T. Oda (eds.), Viral Hepatitis and Liver Disease. Springer-Verlag, Tokyo
  13. Funk, M. L., D. M. Rosenberg, and A. S. F. Lok. 2002. Worldwide epidemiology of HBeAg negative chronic hepatitis B and associated precore and core promoter variants. J. Viral Hepat. 9: 52-61 https://doi.org/10.1046/j.1365-2893.2002.00304.x
  14. Gandhe, S. S., M. S. Chadha, A. M. Walimbe, and V. A. Arankalle. 2003. Hepatitis B virus: Prevalence of precore/core promoter mutants in different clinical categories of Indian patients. J. Viral Hepat. 10: 367-382 https://doi.org/10.1046/j.1365-2893.2003.00445.x
  15. Hadziyannis, S. J., T. Bramou, A. Alexopoulou, and A. Makris. 1991. Immunopathogenesis and natural course of anti-HBe positive chronic hepatitis with replicating B virus, pp. 673-676. In F. B. Hollinger, S. M. Lemon, and H. S. Margolis (eds.). Viral Hepatitis and Liver Disease. Williams and Wilkins, Baltimore
  16. Ikeda, K., Y. Arase, S. Saitoh, M. Kobayashi, T. Someya, T. Hosaka, et al. 2006. Long-term outcome of HBV carriers with negative HBe antigen and normal aminotransferase. Am. J. Med. 119: 977-985 https://doi.org/10.1016/j.amjmed.2006.04.036
  17. Irshad, M. and S. K. Acharya. 1994. Status of hepatic viral markers in patients with acute and chronic liver diseases in northern India. Intervirology 37: 369-372 https://doi.org/10.1159/000150404
  18. Jain, R. C., S. D. Bhat, and S. Sangle. 1992. Prevalence of hepatitis surface antigen among rural population of Loni area in Ahmednagar district of Western Maharashtra. J. Assoc. Physicians India 40: 390-391
  19. Kao, J. H., P. J. Chen, M. Y. Lai, and D. S. Chen. 2002. Clinical and virological aspects of blood donors infected with hepatitis B virus genotypes B and C. J. Clin. Microbiol. 40: 22-25 https://doi.org/10.1128/JCM.40.1.22-25.2002
  20. Lok, A. S. F. 2002. Chronic hepatitis B. N. Engl. J. Med. 346: 1682-1683 https://doi.org/10.1056/NEJM200205303462202
  21. Merican, I., R. Guan, D. Amarapuka, M. J. Alexander, A. Chutaputti, R. N. Chien, et al. 2000. Chronic hepatitis B virus infection in Asian countries. J. Gastroenterol. Hepatol. 15: 1356-1361 https://doi.org/10.1046/j.1440-1746.2000.0150121356.x
  22. Mital, V. N., O. P. Gupta, D. K. Nigam, P. C. Saxena, and S. Kumar. 1980. Pattern of hepatitis B antigen-contact and carrier state in Northern India. J. Indian Med. Assoc. 74: 105-107
  23. Murhekar, M. V., K. M. Murhekar, D. Das, V. A. Arankalle, and S. C. Sehgal. 2000. Prevalence of hepatitis B infection among the primitive tribes of Andaman and Nicobar Islands. Indian J. Med. Res. 111: 199-203
  24. Sarin, S. K., V. Thakur, R. C. Guptan, S. Saigal, V. Malhotra, S. P. Thyagarajan, and B. C. Das. 2001. Profile of hepatocellular carcinoma in India: An insight into the possible etiologic associations. J. Gastroenterol. Hepatol. 16: 666-673 https://doi.org/10.1046/j.1440-1746.2001.02476.x
  25. Sobeslavsky, O. 1980. Prevalence of markers of hepatitis B virus infection in various countries: A WHO collaborative study. Bull. World Health Organ. 58: 621-628
  26. Tandon, B. N., M. Irshad, M. Raju, G. P. Mathur, and M. N. Rao. 1991. Prevalence of HBsAg and anti-HBs in children and strategy suggested for immunisation in India. Indian J. Med. Res. 93: 337-339
  27. Tandon, B. N., S. K. Acharya, and A. Tandon. 1996. Seroepidemiology of HBV and HCV in India. Strategy for control of maternal transmission of HBV and its effect. Screening methods of blood donors for control of post transfusion hepatitis and their effects. Info. Hepatol. Communic. 5: 14-18 https://doi.org/10.1016/S0928-4346(96)82005-6
  28. Tandon, B. N., S. K. Acharya, and A. Tandon. 1996. Epidemiology of hepatitis B virus infection in India. Gut 38: S56-S59 https://doi.org/10.1136/gut.38.Suppl_2.S56
  29. Thyagarajan, S. P., S. Jayaram, and B. Mohanavalli. 1996. Prevalence of HBV in general population of India, pp. 5-16 In S. K. Sarin and A. K. Singhal (eds). Hepatitis B in India: Problems and Prevention. CBS, New Delhi
  30. Valliammai, T., S. P. Thyagarajan, A. J. Zuckerman, and T. J. Harrison. 1995. Precore and core mutations in HBV from individuals in India with chronic infection. J. Med. Virol. 45: 321-325 https://doi.org/10.1002/jmv.1890450315
  31. Whalley, S. A., D. Brown, G. J. M. Webster, R. Jacobs, S. Reignat, A. Bertoletti, C. G. Teo, V. Emery, and G. M. Dusheiko. 2004. Evolution of hepatitis B virus during primary infection in humans: Transient generation of cytotoxic T-cell mutants. Gastroenterology 127: 1131-1138 https://doi.org/10.1053/j.gastro.2004.07.004
  32. Yoo, B. C., J. W. Park, H. J. Kim, D. H. Lee, Y. J. Cha, and S. M. Park. 2003. Precore and core promoter mutations of hepatitis B virus and hepatitis B e antigen negative chronic hepatitis B in Korea. J. Hepatol. 38: 98-103