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Levels of hepatitis B virus replicative intermediate in serum samples of chronic hepatitis B patients

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Abstract

Hepatitis B virus (HBV) cccDNA levels is an absolute marker of HBV replication in the liver of HBV infected patients. This study aimed to quantify the HBV cccDNA levels in sera and liver tissue samples of treatment naïve patients with chronic hepatitis B. Eighty one chronic hepatitis B (CHB) treatment naïve patients were enrolled from January 2009 to June 2011. Total HBV DNA and HBV cccDNA levels were quantified using sensitive real time PCR assay. The mean age of recruited patients was 34 ± 11.5 years. Fifty four (66.7 %) patients were HBeAg negative. Liver tissue samples were available from 2 HBeAg positive and 21 HBeAg negative CHB patients. The amount of total intrahepatic HBV DNA ranged from 0.09 to 1508.92 copies/cell. The median intrahepatic HBV cccDNA was 0.31 and 0.20 copies/cell in HBeAg positive and HBeAg negative cases, respectively. Serum HBV cccDNA was detectable in 85.2 % HBeAg positive and 48.1 % HBeAg negative CHB patients. Median serum HBV cccDNA was 46,000 and 26,350 copies/mL in HBeAg positive and HBeAg negative subjects, respectively. There was a significant positive correlation between the levels of intrahepatic total HBV DNA and intrahepatic HBV cccDNA (r = 0.533, p = 0.009). A positive correlation was also seen between serum HBV cccDNA levels and serum HBV DNA levels (r = 0.871, p < 0.001). It was concluded that serum HBV cccDNA could be detectable in higher proportion of HBeAg positive patients compared to HBeAg negative patients. Moreover, the median level of serum HBV cccDNA was significantly higher in HBeAg positive patients in contrast to HBeAg negative subjects.

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Acknowledgments

The authors have no competing interests. This work was funded by the Indian Council of Medical Research (ICMR), New Delhi, India. (ICMR No: VIR/28/2010-ECD-I). Authors are grateful to ICMR for giving Junior Research Fellowship to Bhupesh Singla (3/1/3JRF-2008/MPD, dated 1/9/2008).

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Authors and Affiliations

  1. Department of Hepatology, Nehru Hospital, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Bhupesh Singla, Bal Krishan Sharma, Shweta Kapil, Yogesh K. Chawla, Radha K. Dhiman & Ajay Duseja

  2. Department of Experimental Medicine & Biotechnology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Anuradha Chakraborti

  3. Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Sunil K. Arora

  4. Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Ashim Das

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  1. Bhupesh Singla
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  2. Anuradha Chakraborti
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Correspondence to Yogesh K. Chawla.

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Singla, B., Chakraborti, A., Sharma, B.K. et al. Levels of hepatitis B virus replicative intermediate in serum samples of chronic hepatitis B patients. Mol Biol Rep 41, 4689–4696 (2014). https://doi.org/10.1007/s11033-014-3339-7

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  • DOI: https://doi.org/10.1007/s11033-014-3339-7

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