对阿德福韦酯自然变异耐药与抗病毒后耐药的慢性乙型肝炎患者血清HBV P基因序列比较

汪莉萍; 韩方正; 李春杨; 闫梅; 张言超; 颜学兵

对阿德福韦酯自然变异耐药与抗病毒后耐药的慢性乙型肝炎患者血清HBV P基因序列比较

徐州医学院附属医院感染性疾病科

基金项目:

江苏省卫生厅2011年科教兴卫工程医学重点人才支持计划[苏卫科教(2011)15号]；

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中图分类号: R512.62
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出版历程
- 出版日期: 2012-08-20

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

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摘要

摘要: 目的通过对慢性乙型肝炎(CHB)患者外周血乙型肝炎病毒(HBV)聚合酶RT区序列分析,观察对阿德福韦酯(ADV)自然变异耐药及继发耐药的异同。方法 PCR产物直接测序法检测78例对ADV耐药患者外周血HBV RT区基因序列。其中曾用ADV治疗患者30例(治疗组),未抗病毒治疗48例(未治疗组),并对两组ADV相关耐药变异位点发生频数进行比较。结果未治疗组ADV耐药的主要变异类型为rtA181V/T 10例(20.8%),rtN/H238T/D/S 10例(20.8%)和rtV214A变异13例(27.1%);而治疗组发生的ADV耐药变异主要为rtA181V/T 16例(53.3%),没有发现rtN/H238T/D/S变异,仅发现1例rtV214A变异。结论CHB患者中存在相当严重的ADV自然变异耐药变异,主要变异类型为rtN/H238T/D/S及rtV214A,而抗病毒治疗后该变异位点发生频数反而相对减少。rtA181V/T变异既可以为自然变异也可以由ADV抗病毒治疗而诱发。
- 阿德福韦酯 /
- 肝炎病毒,乙型 /
- 肝炎,乙型,慢性 /
- 抗药性,多种,病毒
Abstract: 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.
- adefovir dipivoxil /
- hepatitis B virus /
- hepatitis B /
- chronic

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参考文献(14)

[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.

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