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

Xiaoguo Zhang,Yun Wang,Shijun Chen,Shuchun Gao,Wansu Xu,Yizhen Du,Lu Liu

doi:10.3892/etm.2014.2156

Xiaoguo Zhang, Yun Wang + Show 5 more

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https://doi.org/10.3892/etm.2014.2156

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Publication Date: Dec 24, 2014
Citations: 1	License type: CC BY 3.0

Affiliation: Jinan Infectious Disease Hospital, Shandong University

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.

Highlights

Infection of hepatitis B virus (HBV) remains a global health problem
The main mutation associated with L‐nucleoside resistance is rtM204I/V, a mutation that occurs within the YMDD motif of the reverse transcriptase (RT) region of the polymerase [11]
HBV DNA loads of serum and peripheral blood mononuclear cells (PBMCs) in the different groups are shown in Fig. 1 and Table II

Summary

Introduction

Patients with chronic hepatitis B (CHB) can develop progressive liver disease, which can result in cirrhosis and hepatocellular carcinoma (HCC). These stages of the disease are associated with an increased risk of morbidity and mortality, and incur considerable healthcare costs [1]. To reduce morbidity and mortality from chronic HBV infection, antiviral treatment is the only effective approach [2]. Current antiviral agents for the treatment of CHB include interferon (IFN) and nucleoside analogues (NUCs). Treatment with IFN may lead to a durable response, the unpleasant adverse effects and high cost limit its use [3]. NUCs, including lamivudine (LAM) and telbivudine (LdT), become the most common drugs used for antiviral therapy [4]. The main mutation associated with L‐nucleoside resistance is rtM204I/V, a mutation that occurs within the YMDD motif of the RT region of the polymerase [11]

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