中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 3
Mar.  2014
Turn off MathJax
Article Contents

Drug resistance mutations related to nucleos(t)ide analogues in Chinese patients with chronic HBV infection: an analysis of 153 cases 

DOI: 10.3969/j.issn.1001-5256.2014.03.018
Research funding:

 

  • Published Date: 2014-03-20
  • Objective To amplify and determine the hepatitis B virus ( HBV) reverse transcriptase ( RT) sequences of 153 Chinese patients with chronic HBV infection and investigate the drug resistance mutations related to nucleos ( t) ide analogues, and to analyze if there are drug resistance mutations which might lead to tenofovir resistance. Methods A total of 153 patients with chronic HBV infection were divided into two groups: 78 HBV carriers who had never used nucleos ( t) ide analogues ( NAs) and 75 patients with chronic hepatitis B who had been treated with NAs. Their serum samples were used for HBV DNA extraction and RT gene amplification by PCR, and the RT sequences were analyzed to identify the known drug resistance mutations related to NAs and detect the drug resistance mutations related to tenofovir. The obtained data were statistically analyzed using SPSS 19. 0; the Student's t test was used for normally distributed data, and the Wilcoxon's rank sum test for non- normally distributed data. Results Drug resistance mutations related to NAs were detected in 7 cases ( 8. 97%) of the untreated group, but there was no drug resistance mutation related to tenofovir. Drug resistance mutations were detected in 16 cases ( 21. 33%) of the treated group, with rtA181T + rtN236T mutations in one case, which might be related to tenofovir resistance. Conclusion The drug resistance mutation detection rate in untreated group was 8. 97%. The drug resistance mutation detection rate was not significantly correlated with HBV genotype and patient's sex and age in either group. The rtA181T + rtN236T mutations were detected in only one case of the treated group, which indicates a very low rate of pre- existence of tenofovir- related drug resistance mutations in Chinese patients with chronic HBV infection.

     

  • loading
  • [1] PATTERSON SJ, GEORGE J, STRASSER SI, et al.Tenofovir disoproxil fumarate rescue therapy following failure of both lamivudine and adefovir dipivoxil in chronic hepatitis B[J].Gut, 2011, 60 (2) :247-254.
    [2]LEVRERO M, CIMINO L, LAMPERTICO P, et al.Tenofovir (TDF) for chronic hepatitis B patients with suboptimal response to adefovir (ADV) or ADV/LAM treatment:results of the OPTIB Italian multicenter prospective open label study[J].Hepatology, 2010, 52:92A.
    [3] SHELDON J, CAMINO N, RODES B, et al.Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir[J].Antivir Ther, 2005, 10 (6) :727-734.
    [4] AMINI-BAVIL-OLYAEE S, HERBERS U, SHELDON J, et al.The rtA194T polymerase mutation impacts viral replication and susceptibility to tenofovir in hepatitis B e antigen-positive and hepatitis B e antigen-negative hepatitis B virus strains[J].Hepatology, 2009, 49 (4) :1158-1165.
    [5] BRUNELLE MN, JACQUARD AC, PICHOUD C, et al.Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir[J].Hepatology, 2005, 41 (6) :1391-1398.
    [6]KOZIEL MJ, PETERS MG.Viral hepatitis in HIV infection[J].N Engl J Med, 2007, 356 (14) :1445-1154.
    [7]GISH RG, LOCARNINI S.Genotyping and genomic sequencing in clinical practice[J].Clin Liver Dis, 2007, 11 (4) :761-795.
    [8]ZOULIM F, LOCARNINI S.Management of treatment failure in chronic hepatitis B[J].J Hepatol, 2012, 56 (Suppl 1) :s112-122.
    [9]ZHENG J, ZENG Z, ZHANG D, et al.Prevalence and significance of hepatitis B reverse transcriptase mutants in different disease stages of untreated patients[J].Liver Int, 2012, 32 (10) :1535-1542.
    [10]RHEE SY, MARGERIDON-THERMET S, NGUYEN MH, et al.Hepatitis B virus reverse transcriptase sequence variant database for sequence analysis and mutation discovery[J].Antiviral Res, 2010, 88 (3) :269-275.
    [11]XU Z, LIU Y, XU T, et al.Acute hepatitis B infection associated with drug-resistant hepatitis B virus[J].J Clin Virol, 2010, 48 (4) :270-274.
    [12]GAI HP, SUN WX, YUAN DS, et al.The clinical implications of detecting pre-existing resistance to nucleos (t) ide analogue-based antiviral therapy[J].J Clin Hepatol, 2012, 28 (11) :841-844. (in Chinese) 盖洪鹏, 孙伟翔, 袁德胜, 等.预存耐药对核苷 (酸) 类似物抗病毒治疗应答和耐药的影响[J].临床肝胆病杂志, 2012, 28 (11) :841-844.
    [13]TAN Y, DING K, SU J, et al.The naturally occurring YMDD mutation among patients chronically infected HBV and untreated with lamivudine:a systematic review and meta-analysis[J].PLoS One, 2012, 7 (3) :e32789.
    [14]MIN XC, MIAO XH, ZHAO SM, et al.The spontaneous YMDD mutation rate in chronic hepatitis B patients[J].Chin J Hepatol, 2009, 17 (12) :887-890. (in Chinese) 闵晓春, 缪晓辉, 赵书民, 等.慢性乙型肝炎病毒感染者病毒YMDD的自然变异[J].中华肝脏病杂志, 2009, 17 (12) :887-890.
    [15]YANG YL, XIAO P, GAO P, et al.Distribution of HBV genotypes and YMDD mutations in e antigen-positive patients[J].J Clin Hepatol, 2012, 28 (6) :428-430. (in Chinese) 杨彦麟, 肖萍, 高鹏, 等.HBeAg阳性患者中乙肝病毒基因型分布及YMDD变异位点分析[J].临床肝胆病杂志, 2012, 28 (6) :428-430.
    [16]YE XG, WANG RL, GUO HB.Detection of YMDD mutant in patients with chronic hepatitis B before treatment[J].Chin J Lab Med, 2002, 25 (4) :248. (in Chinese) 叶晓光, 王若伦, 郭海波.慢性乙型肝炎患者治疗前YMDD变异基因的检测及分析[J].中华检验医学杂志, 2002, 25 (4) :248.
    [17]QIN B, BUDEUS B, CAO L, et al.The amino acid substitutions rtP177G and rtF249A in the reverse transcriptase domain of hepatitis B virus polymerase reduce the susceptibility to tenofovir[J].Antiviral Research, 2013, 97 (2) :93-100.
    [18]van BMMEL F, de MAN RA, Wedemeyer H, et al.Long-term efficacy of tenofovir monotherapy for hepatitis B virus monoinfected patients after failure of nucleoside/nucleotide analogues[J].Hepatology, 2010, 51 (1) :73-80.
    [19]LIANG ZL, LIU Y, SU HL, et al.Mutations possibly associated with tenofovir disoproxil fumarate resistance in 1740 patients with chronic hepatitis B[J].Infect Dis Info, 2009, 22 (4) :207-210. (in Chinese) 梁兆玲, 刘妍, 苏何玲, 等.1740例慢性乙型肝炎患者替诺福韦酯耐药可能相关突变分析[J].传染病信息, 2009, 22 (4) :207-210.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (2292) PDF downloads(620) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return