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    Malik, Abdul Kumar, Deepak Khan, Abdul Arif Khan, Azmat Ali Chaudhary, Anis Ahmad Husain, Syed Akhtar and Kar, P. 2016. Hepatitis B virus precore G1896A mutation in chronic liver disease patients with HBeAg negative serology from North India. Saudi Journal of Biological Sciences,

    Ozaras, Resat Inanc Balkan, Ilker Yemisen, Mucahit and Tabak, Fehmi 2015. Epidemiology of HBV subgenotypes D. Clinics and Research in Hepatology and Gastroenterology, Vol. 39, Issue. 1, p. 28.


Genetic analysis of precore/core and partial pol genes in an unprecedented outbreak of fulminant hepatitis B in India

  • S. KHARE (a1), S. S. NEGI (a2), S. SINGH (a1) (a2), M. SINGHAL (a2), S. KUMAR (a2), C. PRAKASH (a1), R. VENUGOPAL (a2), D. S. RAWAT (a2), L. S. CHAUHAN (a1) (a2) and A. RAI (a2)
  • DOI:
  • Published online: 15 March 2012

We investigated an unprecedented outbreak of fulminant hepatitis B virus (HBV) that occurred in Modasa, Gujarat (India) in 2009. Genomic analysis of all fulminant hepatic failure cases confirmed exclusive predominance of subgenotype D1. A1762T, G1764A basal core promoter (BCP) mutations, insertion of isoleucine after nt 1843, stop codon mutation G1896A, G1862T transversion plus seven other mutations in the core gene caused inhibition of HBeAg expression implicating them as circulating precore/BCP mutant virus. Two rare mutations at amino acids 89 (Ile→Ala) and 119 (Leu→Ser) in addition to other mutations in the polymerase (pol) gene may have caused some alteration in either of four pol gene domains to affect encapsidation of pregenomic RNA to enhance pathogenicity. Sequence similarity among patients' sequences suggested an involvement of a single hepatitis B mutant strain/source to corroborate the finding of gross and continued usage of HBV mutant-contaminated syringes/needles by a physician which resulted in this unprecedented outbreak of fulminant hepatitis B. The fulminant exacerbation of the disease might be attributed to mutations in the BCP/precore/core and pol genes that may have occurred due to selection pressure during rapid spread/mutation of the virus.

Corresponding author
*Author for correspondence: Dr A. Rai, Ph.D., Joint Director & Head, Division of Biochemistry & Biotechnology, National Centre for Disease Control (NCDC), 22-Sham Nath Marg, Delhi-110054, India. (Email:
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1.ND Thompson , Non-hospital health care-associated hepatitis B and C virus transmission: United States, 1998–2008. Annals of Internal Medicine 2009; 150: 3339.

4.VA Arankalle , An outbreak of hepatitis B with high mortality in India: association with precore, basal core promoter mutants and improperly sterilized syringes. Journal of Viral Hepatitis 2011; 18: e20e28.

5.A Chaudhary , Impact of HIV on genomic variability in the 5′UTR of HCV in Indian patients with HCV/HIV co-infection. Intervirology 2008; 51: 224229.

7.K Tamura , MEGA 4: Molecular Evolutionary Genetic Analysis (MEGA) software version 4.0. Molecular Biology and Evolution 2007; 24: 15961599.

8.M Mondelli , AL Eddleston . Mechanism of liver cell injury in acute and chronic hepatitis B. Seminars in Liver Disease 1984; 4: 4758.

10.R Harpaz , Transmission of hepatitis B virus to multiple patients from a surgeon without evidence of inadequate infection control. New England Journal of Medicine 1996; 334: 549554.

11.PK Chandra , G1862T mutation among hepatitis B virus infected individuals: association with viral genotypes and disease outcome in Kolkata, Eastern India. Intervirology 2007; 50: 173180.

12.T Valliammai , Precore and core mutations in HBV from individuals in India with chronic infection. Journal of Medical Virology 1995; 45: 321325.

13.K Li , Critical role of the 36-nucleotide insertion in hepatitis B virus genotype G in core protein expression, genome replication, and virion secretion. Journal of Virology 2007; 81: 92029215.

14.P Garmiri , Deletions and recombinations in the core region of hepatitis B virus genotype E strains from asymptomatic blood donors in Guinea, West Africa. Journal of General Virology 2009; 90: 24422451.

16.YF Liaw , CM Chu . Hepatitis B virus infection. Lancet 2009; 373: 582–92.

17.MR Brunetto , A new hepatitis B virus strain in patient with severe anti-HBe positive chronic hepatitis B. Journal of Hepatology 1990; 10: 258–61.

18.HE Blum , Naturally occurring missense mutation in the polymerase gene terminating hepatitis B virus replication. Journal of Virology 1991; 65: 18361842.

19.P Vivekanandan , Correlation between hepatitis B genotypes, 1896 precore mutation, virus loads and liver dysfunction in an Indian population. Indian Journal of Gasteroenterology 2008; 27: 142147.

20.V Thakur , Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent. Journal of Gastroenterology and Hepatology 2002; 17: 165–70.

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Epidemiology & Infection
  • ISSN: 0950-2688
  • EISSN: 1469-4409
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