Genotypes and resistance loci in patients with chronic hepatitis B achieving virologic breakthrough in treatment with lamivudine combined with adefovir after developing drug resistance in treatment with lamivudine alone

Yang DongQiang; Chen Fang; Kang Yi; Ding GangQiang; Xiao ErHui; Peng Zhen; Shang Jia

doi:10.3969/j.issn.1001-5256.2016.03.016

Issue 3

Mar. 2016

Turn off MathJax

Article Contents

Abstract

References

Article Navigation > Journal of Clinical Hepatology > 2016 > 32(3): 480-483

PDF( 1653 KB)

Genotypes and resistance loci in patients with chronic hepatitis B achieving virologic breakthrough in treatment with lamivudine combined with adefovir after developing drug resistance in treatment with lamivudine alone

DOI: 10.3969/j.issn.1001-5256.2016.03.016

Center of Infectious Diseases, Henan Provincial People′s Hospital

Research funding:

Published Date: 2016-03-20

Abstract

Abstract

Objective To investigate the genotypes and resistance loci in patients with chronic hepatitis B( CHB) achieving virologic breakthrough in the treatment with lamivudine( LAM) combined with adefovir( ADV) after developing drug resistance in the treatment with LAM alone. Methods A total of 89 CHB patients who were admitted to Henan Provincial People's Hospital and treated with LAM and ADV as the antiviral therapy after developing drug resistance in the treatment with LAM alone from June 2010 to June 2013 were enrolled,and their serum samples were collected. Quantitative real- time PCR was used for hepatitis B virus( HBV) detection,and sequencing was applied to determine the genotype and detect the resistance loci rt N236 T,rt A181 V,rt M204 V,and rt L180 M. The t- test was applied for comparison of continuous data between groups,and the chi- square test was applied for comparison of categorical data between groups. Results LAM rt M204 V mutation was detected in all the 89 patients after treatment with LAM alone. After the combination therapy with LAM and ADV,ADV rt N236 T mutation was detected in 9 patients,ADV rt A181 V mutation in 5 patients,and rt N236 T + rt A181 V mutation in 8 patients,with an overall ADV resistance rate of 24. 7%( 22 /89). As for HBV genotyping,82 patients had genotype C,and rt A181 V + rt N236 T mutation was detected in 8 patients; 7 patients had genotype B. Conclusion Compared with the patients with HBV genotype B,the patients with genotype C are more susceptible to rt A181 V + rt N236 T mutation during the combination therapy with LAM and ADV after developing drug resistance in the treatment with LAM alone.
- hepatitis B,chronic,
- lamivudine,
- adefovir,
- genotype,
- point mutation

FullText(HTML)

References(22)

References

[1] Chinese Society of Hepatology,Chinese Society of Infectious Diseases,Chinese Medical Association.The guideline of prevention and treatment for chronic hepatitis B(2010 version)[J].J Clin Hepatol,2011,27(1):Ⅰ-ⅩⅥ.(in Chinese)中华医学会肝病学分会,中华医学会感染病学分会.慢性乙型肝炎防治指南(2010年版)[J].临床肝胆病杂志,2011,27(1):Ⅰ-ⅩⅥ.

[2]PERRILLO R,SCHIFF E,YOSHIDA E,et al.Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants[J].Hepatology,2000,32(1):129-134.

[3]DONG JY,DONG JG.Clinical efficacy of adefovir dipivoxil combined with anluohuaxian pills on treating compensated cirrhosis patients with chronic hepatitis B[J/CD].Chin J Liver Dis:Electronic Edition,2014,6(4):71-74.(in Chinese)董晋瑛,董晋钢,阿德福韦酯联合安络化纤丸治疗乙型肝炎肝硬化的疗效观察[J/CD].中国肝脏病杂志:电子版,2014,6(4):71-73.

[4]SEGOVIA MC,CHACRA W,GORDON SC.Adefovir dipivoxil in chronic hepatitis B:history and current uses[J].Expert Opin Pharmacother,2012,13(2):245-254.

[5]VIGANO M,LAMPERTICO P,COLOMBO M.Drug safety evaluation of adefovir in HBV infection[J].Expert Opin Drug Saf,2011,10(5):809-818.

[6]WU GH,DING HG,ZENG CQ.Overview of whole genome sequence of HBV in public nucleic acid databases and establishment of HBV consensus sequence in China[J].Progr Nat Sci,2008,18(2):121-129.(in Chinese)吴光华,丁惠国,曾长青.公共核算数据库乙肝病毒全基因组序列概况和中国HBV参照序列的建立[J].自然科学进展,2008,18(2):121-129.

[7]YIN JH,HE YC,LI CZ,et al.Distribution of HBV genotypes and subgenotypes in patients with chronic hepatitis B,hepatocellular carcinoma,asymptomatic HBV carriers and its clinical relevance[J].Acad J Second Military Med Univ,2008,29(1):1-5.(in Chinese)殷建华,何永超,李成忠,等.乙型肝炎病毒感染相关疾病中病毒基因型和亚型的的分布及其与临床指标的关系[J].第二军医大学报,2008,29(1):1-5.

[8]GLEBE D,BREMER CM.The molecular virology of hepatitis B virus[J].Semin Liver Dis,2013,33(2):103-112.

[9] YU S,JIANQIN H,WEI W,et al.The efficacy and safety of nucleos(t)ide analogues in the treatment of HBV-related acute-on-chronic liver failure:a meta-analysis[J].Ann Hepatol,2013,12(3):364-372.

[10]CHEN CH,WANG JH,LU SN,et al.Characteristics of adefovir resistance in patients with or without lamivudine-resistant hepatitis B virus treated with adefovir:a 4-year experience[J].Liver Int,2011,31(2):206-214.

[11]WU S,FUKAI K,IMAZEKI F,et al.Initial virological response and viral mutation with adefovir dipivoxil added to ongoing lamivudine therapy in lamivudine-resistant chronic hepatitis B[J].Dig Dis Sci,2011,56(4):1207-1214.

[12]LI QF,LIU YN,YANG HL,et al.Effects of adefovir dipivoxil combined with lamivudine on HBV DNA duplication and T cell subsets in chronic hepatitis B patients[J].Int J Virol,2014,21(4):168-171.(in Chinese)黎秋芬,刘亚南,杨红丽,等.阿德福韦酯联合拉米夫定对CHB患者HBV DNA复制和T细胞亚群的影响[J].国际病毒学杂志,2014,21(4):168-171.

[13]QI X,XIONG S,YANG H,et al.In vitro susceptibility of adefovir-associated hepatitis B virus polymerase mutations to other antiviral agents[J].Antivir Ther,2007,12(3):355-362.

[14] MINDE Z,YIMIN M,GUANGBI Y,et al.Five years of treatment with adefovir dipivoxil in Chinese patients with HBe Ag-positive chronic hepatitis B[J].Liver Int,2012,32(1):137-146.

[15]YANG JX,LIU BM,LI XG,et al.Profile of HBV antiviral resistance mutations with distinct evolutionary pathways against nucleoside/nucleotide analogue treatment among Chinese chronic hepatitis B patients[J].Antivir Ther,2010,15(8):1171-1178.

[16]MIRANDOLA S,SEBASTIANI G,ROSSI C,et al.Genotype-specific mutations in the polymerase gene of hepatitis B virus potentially associated with resistance to oral antiviral therapy[J].Antiviral Res,2012,96(3):422-429.

[17]BOXALL E,SIRA J,KASKAR S,et al.Does genotype predict response to treatment in children infected with hepatitis B perinatally?[J].J Med Virol,2012,84(10):1535-1540.

[18]KUWAHARA R,KUMASHIRO R,MURASHIMA S,et al.Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy[J].J Med Virol,2004,72(1):26-34.

[19]ASAHINA Y,IZUMI N,UCHIHARA M,et al.Core promoter/pre-core mutations are associated with lamivudine-induced HBe Ag loss in chronic hepatitis B with genotype C[J].J Hepatol,2003,39(6):1063-1069.

[20]YANG LM,PENG J,ZHAO YR,et al.Therapeutic effect of lamivudine in patients with chronic hepatitis B and its association with HBV genotype:an analysis of 136 cases in Qinhuangdao,China[J].Chin J Integr Tradit West Med Liver Dis,2010,6(20):360-362.(in Chinese)杨丽敏,彭勋,赵艳茹,等.秦皇岛市136例慢性乙型肝炎患者拉米夫定的疗效及其与HBV基因型的关系[J].中西医结合肝病杂志,2010,6(20):360-362.

[21]ZHONG L,SHU CL,FENG HQ,et al.Association between HBV genotype and treatment response[J].Zhejiang Clin Med J,2007,9(12):1710-1711.(in Chinese)钟磊,殳长林,冯慧琴,等.HBV基因型与治疗应答的相关性研究[J].浙江临床医学,2007,9(12):1710-1711.

[22]ZHOU DS,LUO GH,JIANG JN,et al.The virology response of lamivudine with HBV genotype B compare with genotype C[J].China Prac Med,2008,3(13):13-14.(in Chinese)周冬生,罗光汉,江建宁,等.B、C基因型与拉米夫定抗HBV疗效的比较[J].中国实用医药,2008,3(13):13-14.

Relative Articles

[1]	Bao Jun, Liang JunCai, Gong Li, Chen XiaoXiao. Clinical efficacy of combined treatment with entecavir and adefovir dipivoxil for lamivudine-resistant chronic hepatitis B[J]. Journal of Clinical Hepatology, 2014, 30(10): 1031-1034. doi: 10.3969/j.issn.1001-5256.2014.10.014
[2]	Huang MeiJin, Tan HouJi, He YanZhuan, Huang QiWen, Zhou YaoNan, Qiu HaiXian. Forty-eight-week efficacy of adefovir dipivoxil alone versus combined with lamivudine in treatment of lamivudine-resistant HBeAg-positive chronic hepatitis B[J]. Journal of Clinical Hepatology, 2014, 30(7): 636-638. doi: 10.3969/j.issn.1001-5256.2014.07.015
[3]	Ruan BingWei, Lu XiaoJu, Lin YanMing, Chen RongCe, Chen XinZhi, Ceng GuangZhong, Liu YanPing. Evaluation of adverse reactions induced by adefovir dipivoxil in 85 chronic hepatitis B patients[J]. Journal of Clinical Hepatology, 2013, 29(2): 104-106.
[4]	Yan HaiMing, Chen JianHua, Ye YiNong, Long Hui, Wang XiangHuai. Clinical effects of lamivudine combined with adefovir dipivoxil and entecavir alone in 48-week treatment of HBeAg-positive chronic hepatitis B:preliminary comparative study[J]. Journal of Clinical Hepatology, 2013, 29(7): 508-511. doi: 1001-5256 (2013) 07-0508-04
[5]	Ma YanHong. Clinical effect of initial combination therapy with lamivudine plus adefovir dipivoxil in 48-week treatment of HBeAg-positive chronic hepatitis B[J]. Journal of Clinical Hepatology, 2013, 29(8): 631-632. doi: 10.3969/j.issn.1001-5256.2013.08.020
[6]	Wang LiPing, Han FangZheng, Li ChunYang, Yan Mei, Zhang YanChao, Yan XueBing. Evaluation of adefovir primary resistance and adefovir repulsive mutations of the HBV DNA P gene in chronic hepatitis B patients[J]. Journal of Clinical Hepatology, 2012, 28(8): 606-608.
[7]	Song MinNing, Huang WenQi, Min Feng, Hong MeiZhu, Fan RongHua, Wu WeiBing, Zhang Li. The efficacy of 3 years adefovir monotherapy in chronic hepatitis B patients with lamivudine resistance[J]. Journal of Clinical Hepatology, 2012, 28(1): 29-32.
[8]	Geng JianZhang, Fan XiaoHong, Lu HaiYing, Li Jing, Tian XiuLan, Xu XiaoYuan. The evaluation of de novo combination of antiviral treatment to hepatitis B patients with decompensated cirrhosis[J]. Journal of Clinical Hepatology, 2011, 27(8): 837-839+843.
[9]	Gu QiangYe, Li Qin, Ge XiuLin. Observation of long-term efficacy of different treatment protocol of Adefovir dipivoxil in chronic hepatitis B patients with Lamivudine-resistance[J]. Journal of Clinical Hepatology, 2011, 27(4): 411-413.
[10]	Liu LongGen, Ye ChunYan, Tong XueCheng. Maintenance of negative HBV DNA in patients with chronic hepatitis B during 96 weeks followup with active replacement of Adefovir dipivoxil with Lamivudine[J]. Journal of Clinical Hepatology, 2011, 27(3): 292-294.
[11]	Luo LiSha, Zhang JiWan, Zhou JianLi, Kang Ning, He PengFei, Long Li, Zhang XiaoFang, Zhao ZhiYong, Wang HaiBin. Changes on the spots mutation of complement receptor type 1 and on erythrocytes immune adhesion function in HBeAg positive hepatitis patients[J]. Journal of Clinical Hepatology, 2010, 26(6): 635-637.
[12]	Zhu FeiYan. The clinical effect Adefovir dipivoxil in Lamivudine resistant HBeAg positive chronic hepatitis B patients[J]. Journal of Clinical Hepatology, 2010, 26(5): 517-518.
[15]	Cao TianGao, Li JingNan, Shi YunZhen, Li ChaoXia. The clinical study of foscarnet sodium combined with adefovir dipivoxil for lamivudine-resistant patients with chronic hepatitis B[J]. Journal of Clinical Hepatology, 2008, 24(4): 248-250.
[16]	Li Jun, Chen XinYue, Zhao Hong, Yu YanYan, Si ChongWen, Han ZhongHou, Zhang WenJin, Chen YuPing, Chen Yong, Wang GuiQiang, Yu Min, Gong WeiBo, Xu JingHang, Wang Jun, Lin XiaoHong, Li XueYing. The relationship of hepatitis B virus genotypes and efficacy of lamivudine and interferon alpha 2b in the treatment of HBeAg-positive chronic hepatitis B[J]. Journal of Clinical Hepatology, 2008, 24(3): 169-171.
[19]	Jiang Jun, Mou XiaoHui, Cai Xiong. Comparative study of adefovir dipivoxil and lamivudine on serum IFN-γ and IL-4 in patients with chronic hepatitis B[J]. Journal of Clinical Hepatology, 2007, 23(3): 176-178.
[20]	Xu ZhengJu, Yang Hong, Zhang QiHua, Chen XianLi, Li ShuQing, Wang ChongGuo. Study on the relationship between hepatitis B virus genotypes and effect of lamivudine therapy.[J]. Journal of Clinical Hepatology, 2005, 21(3): 157-159.

Supplements(0)

Cited By

Cited by

Periodical cited type(3)

1.	胡翠兰. 干扰素联合阿德福韦酯治疗对拉米夫定耐药的乙型肝炎患者临床效果分析. 中外医学研究. 2019(03): 20-22 .
2.	李博，郑欢伟，赵召霞，李健霞，许剑萍，金鹏. 干扰素α-1b序贯拉米夫定联合治疗对慢性乙型肝炎患儿T淋巴细胞亚群、补体水平及肝功能的影响. 中国医药导报. 2019(14): 148-151 .
3.	陈容娟，刘妍，李晓东，杜凤霞，思兰兰，李乐，许智慧，姚增涛，戴久增，徐东平，段昌柱. 拉米夫定和阿德福韦酯双重耐药HBV株临床检出特点与表型特性分析. 传染病信息. 2018(03): 215-219 .

Other cited types(0)

Proportional views

Proportional views

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

Get Citation

PDF

XML

Article Metrics

Article views (2382) PDF downloads(419)

Genotypes and resistance loci in patients with chronic hepatitis B achieving virologic breakthrough in treatment with lamivudine combined with adefovir after developing drug resistance in treatment with lamivudine alone

DOI: 10.3969/j.issn.1001-5256.2016.03.016