中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 8
Aug.  2012
Turn off MathJax
Article Contents

Evaluation of adefovir primary resistance and adefovir repulsive mutations of the HBV DNA P gene in chronic hepatitis B patients

Research funding:

 

  • Published Date: 2012-08-20
  • Objective To determine if adefovir resistance associated with the HBV DNA P gene in chronic hepatitis B patients (CHB) results from primary or adefovir-induced mutations. Methods Seventy-eight chronic HBV patients were enrolled in the study, including 30 patients who accepted adefovir treatment and 48 patients who refused any type of nucleoside analog (NA) treatment.Serum samples from all participants were genotyped for the HBV DNA P gene by PCR amplification and automated sequencing. Results In the group of untreated patients, the main mutations were rtA181V/T10 (20.8%) , rtN/H238T/D/S10 (20.8%) , and rtV214A 13 (27.1%) .In the group of adefovir-treated patients, the main mutation was rtA181V/T16 (53.3%) , no rtN/H238T/D/S mutant was detected, and only one patient carried the rtV214A mutant of the HBV RT region. Conclusion CHB patients carry adefovir-resistance mutations that arise spontaneously, as detected in untreated patients.These resistance mutations mainly included rtV214A and rtN/H238T/D/S.However, CHB patients treated with adefovir carried less resistance mutations overall but had a much higher incidence of the rtA181V/T mutation, suggesting that this mutation may be primary or induced by adefovir.

     

  • loading
  • [1]Locarnini S, Qi X, Arterburn S, et al.Incidence and predic-tors of emergence of HBV mutations associated with ADV re-sistance during 4 years of adefovir therapy for patients withchronic HBV[J].Hepatology, 2006, 41:A36.
    [2]杨海红, 曾文铤, 卫建筠.乙型肝炎病毒基因型与拉米夫定疗效关系研究[J].热带医学杂志, 2006, 6 (2) :215-216.
    [3]Angus P, Vaughan R, Xiong S, et al.Resistance to adefovir-dipivoxil therapy associated with the selection of a novel mu-tation in the HBV polymerase[J].Gastroenterology, 2003, 125 (2) :292.
    [4]Qi X, Snow A, Thibault V, et al.Longterm incidence of adefovirdipivoxil resistance in chronic hepatitis B patients after 144weeks of therapy[J].Hepatology, 2004, 40 (suppl1) :57.
    [5]Perrillo R, Hann HW, Mutimer D, et al.Adefovir dipivoxil addedto ongoing lamivudine in chronic hepatitis B with YMDD mutanthepatitis B virus[J].Gastroenterology, 2004, 126 (1) :81.
    [6]Barcena R, Del Campo S, Moraleda G, et al.Study on theefficacy and safety of adefovir dipivoxil treatment in post livertransplant patients with hepatitis B virus infection and lamivu-dine resistant hepatitis B virus[J].Transplant Proc, 2005, 37 (9) :3960-3962.
    [7] 汪莉萍, 韩方正, 李春杨, 等.慢性乙型肝炎患者抗病毒治疗前HBV P区基因序列测定的意义[J].中华临床感染病杂志, 2011, 4 (5) :298-300.
    [8]Kobayashi S, Ide T, Sata M.Detection of YMDD motif muta-tions in some lamivudine-untreated asymptomatic hepatitisB virus carriers[J].Hepatology, 2001, 34 (4) :584-586.
    [9]Heo J, Cho M, Kim HH, et al.Detection of YMDD motifmutants by oligonucleotide chips in lamivudine untreated pa-tients with chronic hepatitis B virus infection[J].J KoreanMed Sci, 2004, 19 (4) :541-546.
    [10]孙海平, 王磊, 杨芳.核苷 (酸) 类似物相关H BV P基因耐药变异焦磷酸测序[J].山东大学医学报:医学版, 2010, 48 (5) :85-88.
    [11]Mirandola S, Campagnolo D, Bortoletto G, et al.Large-scalesurvey of naturally occurring HBV polymerase mutations associat-ed with anti-HBV drug resistance in untreated patients with chro-nic hepatitis B[J].J Viral Hepat, 2011, 18 (7) :e212-216.
    [12]Ismail AM, Samuel P, Eapen CE, et al.Antiviral resistancemutations and genotype-associated amino acid substitu-tions in treatment-nave hepatitis B virus-infected individu-als from the Indian subcontinent[J].Intervirology, 2012, 55 (1) :36-44.
    [13]Yeh CT, Chien RN, Chu CM, et al.Clearance of the originalhepatitis B virus YMDD motif mutants with emergence of dis-tinct lamivudine-resistantmutants during prolonged lamivudinetherapy[J].Hepatology, 2000, 31 (6) :1318-1326.
    [14]Bartholomcusz A, Locarnini SA.Antiviral drug resistance:clinical consequences and molecular aspects[J].SeminLiver Dis, 2006, 26 (2) :162-170.
  • 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 (3126) PDF downloads(691) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return