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Clinical implication and viral mutation in basal core promoter/pre-core of hepatitis B virus C/D recombinant

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Abstract

Background and aim

Hepatitis B virus (HBV) C/D recombinant is predominant in Tibet in Western China. Although the geographical and ethnic distributions of the C/D recombinant have been described, the clinical implication and the characteristics of viral mutation in the basal core promoter (BCP)/pre-core (PC) region remain unclear.

Methods

A total of 174 chronic HBV carriers, including 115 with chronic hepatitis B, 45 with liver cirrhosis, and 14 with hepatocellular carcinoma, were enrolled. Using next-generation sequencing, the S and BCP/PC genes were determined and analyzed.

Results

Genotypes B, C2, D, and C/D recombinant were detected in 1.1% (2/174), 19.5% (34/174), 0.6% (1/174) and 78.7% (137/174) of the patients, respectively. The clinical parameters and viral mutation frequency in the BCP/PC region were compared between C2- and C/D recombinant-infected patients. The distribution of C2 and C/D did not differ by disease status or liver function. Significantly higher levels of HBV DNA (6.7 ± 1.6 vs. 5.9 ± 1.5, p = 0.014), HBeAg (263.5 vs. 20.0, p = 0.013) and A1762T/G1764A double-mutations (81.0 vs. 61.8%, p = 0.018), but a lower frequency of G1896A stop mutation (33.6 vs. 76.5%, p < 0.001) was observed in patients with the C/D recombinant than in patients with genotype C2. The clonal frequencies of A1762T, G1764A, G1896A and A1846T were lower in patients with C/D than C2.

Conclusion

The C/D recombinant has different mutation pattern in the BCP/PC region compared with genotype C2. The lower clonal frequencies of BCP/PC mutations may explain the higher levels of HBV DNA and HBeAg in C/D-infected patients.

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Acknowledgements

This work was supported by the Science and Technology Planning Project of Qinghai Province (2015-ZJ-755), China.

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Authors and Affiliations

  1. Department of Infectious Diseases, Qinghai Provincial Infectious Diseases Hospital, Xining, China

    Hua Li, Qilu She, Yuehe Ding, Shenghua Shi & Jijie Li

  2. Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China

    Yu Liu & Zhanhui Wang

  3. State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China

    Hongkai Wu

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  1. Hua Li
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Correspondence to Zhanhui Wang.

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Conflict of interest

Hua Li, Qilu She, Yu Liu, Yuehe Ding, Shenghua Shi, Jijie Li, Hongkai Wu and Zhanhui Wang declare that they have no conflicts of interest to disclose.

Ethical approval

The study was conducted in accordance with the Helsinki Declaration of 1975 and approved by the Ethics Committee of Qinghai Provincial Infectious Diseases Hospital.

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Li, H., She, Q., Liu, Y. et al. Clinical implication and viral mutation in basal core promoter/pre-core of hepatitis B virus C/D recombinant. Hepatol Int 12, 447–455 (2018). https://doi.org/10.1007/s12072-018-9885-7

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  • DOI: https://doi.org/10.1007/s12072-018-9885-7

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