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Intracellular levels of hepatitis B virus DNA and mutational patterns of the polymerase gene of hepatitis B virus in peripheral blood mononuclear cells of patients with lamivudine or telbivudine resistance.

EXPERIMENTAL AND THERAPEUTIC MEDICINE(2015)

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Abstract
Studies are limited regarding the association between the quantity of hepatitis virus B (HBV) DNA loads in serum and peripheral blood mononuclear cells (PBMCs) in patients with drug resistance and few studies focus on the mutational pattern of the polymerase gene of HBV in PBMCs of patients with drug resistance. The aim of the present study was to investigate the association between the quantity of HBV DNA loads in serum and PBMCs in patients with lamivudine (LAM) or telbivudine (LdT) resistance and to explore the mutational pattern of the polymerase gene of HBV in PBMCs of these patients. A total of 51 patients underwent antiviral therapy with LAM or LdT for at least half a year. The present study applied quantitative polymerase chain reaction for the quantification of total HBV DNA, and direct sequencing was used to detect the mutation. In total, 31 patients (60.78%) were detected to have drug resistance. The mean serum HBV DNA levels were significantly higher than the HBV DNA levels of PBMCs, whether in patients with LAM or LdT resistance. The PBMCs HBV DNA loads were correlated with the serum HBV DNA loads in the two groups. Three and two mutational patterns were found in the serum of patients with LAM and LdT resistant, respectively. In total, 85.71% of patients with LAM resistance and 75.00% of patients with LdT resistance presented the same mutational pattern in paired PBMCs and serum. The HBV DNA levels in the PBMCs of patients with LAM or LdT resistance were significantly lower than those in serum and there were positive correlations between them. The majority of the mutational patterns of the polymerase gene of HBV DNA in PBMCs were the same as those in the paired serum. These findings may help to increase knowledge regarding HBV drug resistance.
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Key words
hepatitis B virus,peripheral blood mononuclear cells,hepatitis B virus DNA,lamivudine,telbivudine,resistance,mutation pattern
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