[1]黄书明,曹亚丽,陈 琳.南通地区乙型肝炎病毒P区耐药突变与基因型及其临床意义[J].现代检验医学杂志,2016,31(05):103-106.[doi:10.3969/j.issn.1671-7414.2016.05.028]
 HUANG Shu-ming,CAO Ya-li,CHEN Lin.Drug Resistance Mutations and Genotypes of Hepatitis B Virus P in Nantong Area and Its Clinical Significance[J].Journal of Modern Laboratory Medicine,2016,31(05):103-106.[doi:10.3969/j.issn.1671-7414.2016.05.028]
点击复制

南通地区乙型肝炎病毒P区耐药突变与基因型及其临床意义()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第31卷
期数:
2016年05期
页码:
103-106
栏目:
论著
出版日期:
2016-10-21

文章信息/Info

Title:
Drug Resistance Mutations and Genotypes of Hepatitis B Virus P in Nantong Area and Its Clinical Significance
文章编号:
1671-7414(2016)05-103-04
作者:
黄书明曹亚丽陈 琳
南通市第三人民医院,江苏南通 226006
Author(s):
HUANG Shu-mingCAO Ya-liCHEN Lin
the Third People's Hospital of Nantong,Jiangsu Nantong 226006,China
关键词:
肝炎病毒 乙型 基因型 耐药突变
分类号:
R512.62; Q754
DOI:
10.3969/j.issn.1671-7414.2016.05.028
文献标志码:
A
摘要:
目的 探讨南通地区乙型肝炎病毒P区耐药基因突变特征与基因型,为临床合理用药提供科学依据。方法 选择158例经核苷(酸)类似物治疗至少2年以上慢性乙型肝炎(CHB)患者和30例未接受过核苷(酸)类似物治疗的CHB患者作为研究对象,采用PCR产物直接测序法检测HBV P区耐药基因和基因型,同时观察三种主要突变模式与ALT和HBV DNA水平的关系。结果 158例CHB患者检出B基因型42例(26.58%),C基因型116例(73.42%)。131例发生P区不同位点突变,突变率为82.91%。共检出11个HBV突变位点,主要突变位点是M204I,L180M,M204V,A181V和A181T,耐药频率依次为41.14%,37.34%,22.15%,11.39%和10.13%,11个突变位点有21种突变模式。拉米夫定(LAM)耐药相关突变中以L180M和M204V合并出现为主,其次以M204I单独出现; 阿德福韦酯(ADV)耐药相关突变中以A181V为主; 恩替卡韦(ETV)耐药率较低。结论 南通地区HBV基因型以B和C型为主,C型为优势基因型; 耐药突变主要集中在拉米夫定和阿德福韦酯耐药相关的突变位点,而恩替卡韦耐药率较低。多位点耐药突变检测有助于及时发现病毒耐药,更好地指导临床治疗。
Abstract:
Objective To investigate the mutation characteristics and genotype of hepatitis B virus resistance gene in Nantong area,andprovide scientific basis for clinical rational drug.Methods A total of 158 cases of chronic hepatitis B(CHB)patients who were received with nucleos(T)ide analogues therapy for at least 2 years as the research object,and 30 cases of CHB patients who were not received nucleos(T)ide analogues for the treatment as the control group.PCR-sequencing method was used to detect the HBV P resistant gene and genotype,meanwhile,observe the relationshipbetween three main mutation model and the levels of ALT and HBV DNA was also investigated.Results B genotype was detected in 42(26.58%)out of 158 CHB patients,and 116 cases(73.42%)were C genotype.A total of131 patients with different site mutations in P region,the mutation rate were 82.91%.There were totally 11 HBV mutation sites,including the main mutation site:M204I,L180M,M204V,A181V and A181T,the frequency of drug resistance were41.14%,37.34%,22.15%,11.39% and 10.13%,respectively.Moreover,11 mutation sites had 21 mutation patterns.In lamivudine(LAM)resistance associated mutations,the L180M and M204V sites were mainly co-occurrence,followed by M204Ialone.In adefovir dipivoxil(ADV)resistance associated mutations,A181V was the main mutation site.Whereas,the drug resistance rate of entecavir(ETV)waslow.Conclusion The main genotypes of HBV were type B and C in Nantong area,and C type was the dominant genotype.The resistance mutations mainly concentrated in LAM and ADV resistance associated mutations,while the resistance rate of ETV was low.Multi-locus drug-resistant mutation detection may help to detect viral resistance and guide clinical treatment better.

参考文献/References:

[1] 古丽娣,张 丹,曾惠玲.核苷(酸)类似物治疗引起乙肝病毒耐药相关基因位点突变的总结分析[J].现代检验医学杂志,2013,28(1):122-123. Gu LD,Zhang D,Zeng HL.Summative analysis of drug resistant genetic mutation on nucleoside(Acid)analog anti-HBV[J].J Mod Lab Med,2013,28(1):122-123.
[2] Strasfeld L,Chou S.Antiviral drug resistance: mechanisms and clinicalimplications[J].Infect Dis Clin North Am,2010,24(2):413-437.
[3] 张 玲,吴昊鹤.核苷类似物耐药后乙型肝炎治疗的研究进展[J].临床医学,2011,31(1):104-105. Zhang L,Wu HH.Research progress of hepatitis B treatment about nucleoside analogues resistance later[J].Clin Med,2011,31(1):104-105.
[4] 中华医学会肝病学会 中华医学会感染病学会.慢性乙型肝炎防治指南(2010年版)[J].中华肝胆病杂志(电子版),2011,3(1):40-55. Chinese Society of Hepatology and Chinese Society of Infectious Diseases,Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B(2010version)[J].Chinese JournalHepatology(Electronic Vorsion),2011,3(1):40-55.
[5] 徐东平.乙型肝炎病毒耐药的检测方法与临床意义[J].解放军医学杂志,2010, 35(6):611-613. Xu DP.Techniques and clinical significance of determination of drugresistance of hepatitis B virus[J].Medical Journal of Chinese People's Liberation Army,2010,35(6):611-613.
[6] 孔令和,高素香,柯云霞,等.PCR产物直接测序检测乙型肝炎病毒耐药变异位点[J].南方医科大学学报,2012,32(2):277-279. Kong LH,Gao SX,Ke YX,et al.Clinical application of DNA sequencing for detecting point mutations in hepatitis B virus associated with drug resistance[J].J South Med Univ,2012,32(2):277-279.
[7] 李晓东,李庆虹,李 进,等.华北地区HBV基因亚型特点及其与核苷(酸)类抗HBV药物耐药突变的关系[J].解放军医学杂志,2010,35(6):629-634. Li XD,Li QH,Li J,et al.Characteristics of HBV subgenotypes in North China and their relationship with the mutation of anti-HBV nucleoside resistant analogs[J].Med J Clin PLA,2010,35(6):629-634.
[8] 阎纳新,霍建峰,芦 飞,等.石家庄地区乙型肝炎病毒基因分型及P区耐药基因突变分析[J].中国医院药学杂志,2015,35(4):336-338,362. Yan NX,Huo JF,Lu F,et al.Analysis of HBV genotypes and mutationpatterns of HBV P gene in Shijiazhuang region[J].China Journal of Hospital Pharm J,2015,35(4):336-338,362.
[9] Margeridon Thermet S,Shulman NS,Ahmed A,et al.Ultra deep pyrosequencing of hepatitis B virus quasispecies from nucleoside and nucleotide reverse transcriptase inhibitor(NRTI)treated patients and NRTI nave patients[J].J Infect Dis,2009,199(9):1275-1285.
[10] 娄红梅,刘洪海.乙型肝炎病毒基因自然变异耐药性与HBV DNA,HBeAg,ALT及AST相关因素分析[J].广东医学,2012,33(9):1279-1281. Lou HM,Liu HH.Relationship between HBV polymerase gene pre-existing resistance mutation and HBV-DNA,HBeAg,ALT,AST[J].Guangdong Medical Journal,2012,33(9):1279-1281.
[11] 王 莹,雷 君,许绿叶.乙型肝炎病毒多聚酶区耐药突变位点研究进展[J].中华临床医师杂志(电子版),2013,7(23):10902-10904. Wang Y,Lei G,Xu LY.Research progress of the HBV drug-resistant mutations in the HBV polymerase region[J].Chin J Clinicians(Electronic Edition),2013,7(23):10902-10904.
[12] 赵淑娟,薛 昀,秦玉花.核苷(酸)类似物耐药相关位点分析[J].中国医院药学杂志,2012,32(2):145-146. Zhao SJ,Xue Y,Qin YH.Analysis of drug resistance related sites of nucleoside(acid)analogues[J].China Journal of Hospital Pharm,2012,32(2):145-146.
[13] 付丽娟,滕 旭,谷鸿喜.核苷(酸)类似物抗乙型肝炎耐药机制及临床策略[J].中国医药,2013,8(10):1513-1514. Fu LJ,Teng X,Gu HX.Drug resistance mechanism and clinical strategy of nucleoside(acid)analogues against hepatitis B[J].China Medicine,2013,8(10):1513-1514.
[14] Zoulim F,Locarnini S.Hepatitis B virus resistance to nucleos(t)ide analogues[J].Gastroenterology,2009,137(5):1593-1608.

备注/Memo

备注/Memo:

作者简介:黄书明(1972-),男,副主任技师,Tel:18912288899,E-mail:sanyuanhsm@163.com。
通讯作者:曹亚丽(1981-),女,主管技师,Tel:13962959002,E-mail:873508805@qq.com。
更新日期/Last Update: 2016-10-30