乙型肝炎病毒阿德福韦酯耐药相关变异的研究进展*

doi:10.3969/j.issn.1672-5069.2015.02.029

Abstract

Abstract: Adefovir dipivoxil（ADV）,an oral nucleotide analogue,remains as one of the major antiviral agents in the treatment of chronic hepatitis B（CHB） in China. However,long-term therapy with ADV may lead to hepatitis B virus（HBV） drug-resistant mutations. The signature mutations associated with ADV resistance are rtA181V and rtN236T. The newly-identified ADV primary resistant mutations are rtA181S,rtE218G and rtN236V. In addition,some other mutations including rtA181T,rtV214A, rtQ215H/P/S,rtL217R/P,rtI233V,and rtN238T/D/H remain contradictory,and these mutations need to be further identified.

Key words: hepatitis B virus, Adefovir dipivoxil, Drug resistance, Gene mutation, Antiviral therapy

YE Xiaoling, LIU Yan, XU Dongping.. Research progress of drug-resistant mutations associated with adefovir dipivoxil of hepatitis B virus[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(3): 312-316.

References

[1] Masaru E,Hiroyasu M,Akihiro T,et al. Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B.World J Gastroenterol,2014,20（34）:12031-12038.
[2] 徐东平, 刘妍. 结合基因型耐药突变检测与表型耐药分析探索乙肝病毒耐药的新认识. 解放军医学杂志,2012,37（6）:535-538.
[3] Segovia MC,Chacra W,Gordon SC. Adefovir dipivoxil in chronic hepatitis B:history and current uses. Expert Opin Pharmacother,2012,13（2）:245-254.
[4] 成军. 现代肝炎病毒分子生物学. 北京:北京科学出版社, 2009:944-957.
[5] Li W, Zhao J,Zou Z,et al. Analysis of hepatitis B virus intrahepatic covalently closed circular DNA and serum viral markers in treatment-naive patients with acute and chronic HBV infection. Plos one, 2014, 9（2）:1-9.
[6] 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）. 中华肝脏病杂志,2011,19（1）:13-24.
[7] Angus P,Vaughan R,Xiong S et al. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase. Gastroenterology,2003,125（2）:292-297.
[8] Borroto-Esoda K,Miller MD,Arterburn S. Pooled analysis of amino acid changes in the HBV polymerase in patients from four major adefovir dipivoxil clinical trials. J Hepatol,2007,47（4）:492-498.
[9] Zhou X,Kuang X,Wang Y,et al. Factors influencing inadequate or suboptimal response to adefovir with or without genotypic resistance. J Med Virol,2012,84（7）:1030-1036.
[10] Villet S, Pichoud C,Zoulim F,et al. Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure. J Hepatol,2008,48（5）:747-755.
[11] Liu Y,Li X,Xin S,et al. The rtA181S mutation of hepatitis B virus primarily confers resistance to adefovir dipivoxil. J Viral Hepat,2014,8（14）:1-7.
[12] Lok AS,Zoulim F,Locarnini S,et al.Antiviral drug-resistant HBV:standardizetion of nomenclature and assays and recommendations for management. Hepatology,2007,46（1）:254-265.
[13] Liu L,Wang J,Du C,et al. rtE218G,a novel hepatitis B virus mutation with resistance to adefovir dipivoxil in patients with chronic hepatitis B. J Viral Hepat,2010,17（1）:66-72.
[14] Liu Y,Liu W,Xu D,et al. Screening and identification of a novel adefovir dipivoxil resistance associated mutation, rtN236V,of HBV from a large cohort of HBV-infected patients. Antivir Ther,2014,4（8）:1-8.
[15] Song B,Cui X,Shin J,et al. Response to adefovir depends on mutation patterns in precore region,basal core promoter and reverse transcriptase,and on-treatment responses in lamivudine-resistant chronic hepatitis B patients. Intervirology, 2010,53（4）:203-210.
[16] Chen C,Lee C,Tung W,et al. Evolution of full length HBV sequences in chronic hepatitis B patients with sequential lamivudine and adefovir dipivoxil resistance. J Hepatol,2010,52（4）:478-485.
[17] Gish R, Jia JD,Zoulim F,et al. Selection of chronic hepatitis B therapy with high barrier to resistance. Lancet Infect Dis, 2012,12（4）:341-353.
[18] European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection. J Hepatol,2012,57（1）:167-185.
[19] Li X,Liu Y,Liu L,et al. Analysis of clinical profile and implications of hepatitis B virus rtA181T mutation. Hepatol Int, 2014,8:S101.2014 APASL.
[20] Ahn S,Park Y,Kim K,et al. The impact of the hepatitis B virus polymerase rtA181T mutation on replication and drug resistance is potentially affected by overlapping changes in surface gene. J Virol,2014,88（12）:6805-6818.
[21] Yeh CT,Chen T,Hsu CW,et al. Emergence of the rtA181T/sW172* mutant increased the risk of hepatoma occurrence in patients with lamivudine-resistant chronic hepatitis B. BMC Cancer,2011,11:398.
[22] 胡爱荣, 蒋素文, 梁晓岳, 等. 浙江省东部地区慢性乙型肝炎病毒感染者阿德福韦酯相关位点病毒变异的临床特征分析, 中华医学杂志,2012,92（27）:1878-1881.
[23] Westland CE,Yang H,Delaney WE 4th,et al. Week 48 resistance surveillance in two phase 3 clinical studies of adefovir dipivoxil for chronic hepatitis B. Hepatology,2003,38（1）:96-103.
[24] Salpini R,Svicher V,Cento V,et al. Characterization of drug-resistance mutations in HBV D-genotype chronically infected patients,naive to antiviral drugs. Antiviral Research,2011, 92（2）:382-385.
[25] Sayan M,Sentürk O,Akhan S,et al. Monitoring of hepatitis B virus surface antigen escape mutations and concomitantly nucleos（t）ide analog resistance mutations in Turkish patients with chronic hepatitis B. Int J Infect Dis,2010,14（3）:136-141.
[26] Amini-Bavil-Olyaee S,Herbers U,Tacke F,et al. Prevalence,viral replication efficiency and antiviral drug susceptibility of rtQ215 polymerase mutations within the hepatitis B virus genome. J Hepatol,2009,51（4）:647-654.
[27] Rodriguez-Frias F,Jardi R,Esteban R,et al. Adefovir for chronic hepatitis B treatment: identification of virological markers linked to therapy response. Antivir Ther,2008,13（8）:991-999.
[28] JI D,Liu Y,Xu D,et al. Variable influence of mutational patterns in reverse-transcriptase domain on replication capacity of hepatitis B virus isolates from antiviral-experienced patients. Clin Chim Acta,2011,412（3-4）:305-313.
[29] Schildgen O,Sirma H,Funk A,et al. Variant of hepatitis B virus with primary resistance to adefovir. N Engl J Med, 2006,354（17）:1807-1812.
[30] Schildgen O,Olotu C,Funk A,et al. Selection and counterselection of the rtI233V adefovir resistance mutation during antiviral therapy. J clin microbiol,2010,48（2）:631-634.
[31] Geipel A,Glebe D,Will H,et al. Hepatitis B virus rtI233V mutation and resistance to adefovir. N Engl J Med,2014,370（17）:1667-1668.
[32] Curtis M,Zhu Y,Borroto-Esoda K. Hepatitis B virus containing the I233V mutation in the polymerase reverse-transcriptase domain remains sensitive to inhibition by adefovir. J Infect Dis, 2007,196（10）:1483-1486.
[33] Ismail AM,Sharma OP,Kumar MS,et al. Impact of rtI233V mutation in hepatitis B virus polymerase protein and adefovir efficacy:Homology modeling and molecular docking studies. Bioinformation,2013,9（3）:121-125.
[34] 邓俊, 于德敏, 张欣欣, 等. 乙型肝炎病毒P基因反转录酶区I233V变异对阿德福韦酯耐药的实验研究. 中华传染病杂志, 2011,29（3）:129-133.
[35] 朱华, 钟彦伟, 徐东平, 等. 乙型肝炎病毒rtN238H变异与阿德福韦酯耐药的相关性研究. 实用肝脏病杂志,2011,14（5）:327-329.
[36] Zhong Y,Lv J,Zhou X,et al. Prevalence,virology and antiviral drugs susceptibility of hepatitis B virus rtN238H polymerase mutation from 1865 Chinese patients with chronic hepatitis B. Antiviral Res,2012,93（1）:185-190.
[37] Yuen MF,Lai CL. Treatment of chronic hepatitis B: evolution over two decades. Gastroenterol Hepatol,2011,26（1）:138-143.
[38] 罗先平,经继生,陈红波,等. 干扰素联合阿德福韦酯治疗慢性乙型肝炎2年随访. 肝脏,2010,15（3）:233-234.

Research progress of drug-resistant mutations associated with adefovir dipivoxil of hepatitis B virus

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Shi Yingying, Wang Yuanxi.. Impact of combination telbivudine and adefovir dipivoxil on renal functions in the treatment of patients with chronic hepatitis B [J]. Journal of Practical Hepatology, 2019, 22(6): 820-823.
[2]	Han Meiling, Chen Ping. Antiviral therapy in patients with liver cirrhosis and thrombocytopenia [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(4): 466-469.
[3]	Zhang Qian, Hu Peng. Highlights in antiviral therapy for chronic hepatitis B [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(3): 313-317.
[4]	Zhang Huanhuan, Yang Huan, Shen Silan, et al.. Distribution of HBV genotypes and drug-resistant mutations in patients with chronic hepatitis B [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(1): 41-44.
[5]	Xu Jing, Tao Linlin, Ye Jiaojiao, et al.. Impact of terbivudine combined with adefovir dipivoxil therapy on renal functions in patients with decompensated hepatitis B liver cirrhosis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2019, 22(1): 89-92.
[6]	Chen Xin, Chen Lidong, Li Tinghong.. Rescue therapy by tenofovir disoproxil in hepatitis B liver cirrhotics with multiple drug resistant infection [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(5): 681-684.
[7]	ZhangLining, Liu Zhigang, GaoCaixia, et al.. Application of dietary intervention with authorized education in patients with hepatitis B virus associated glomerulonephritis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(5): 799-800.
[8]	Ming Quan, Wang Shuping, Li Chunyu, et al. Comparative study of denovo or afterward combination of lamivudine and defovir dipivoxil in the treatment of hepatitis B patients with decompensated liver cirrhosis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(4): 627-628.
[9]	Wang Ping, Zhou Xiaojia, Liu Xinhua. Application of video-based health education in patients with hepatitis B virus associated glomerulonephritis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(3): 451-452.
[10]	Wei Yu, Li Huahe, Zhang Xianbo. Comparison of short-term efficacy and adverse effects between entecavir and adefovir dipivoxil in the treatment of patients with chronic hepatitis B [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(3): 453-454.
[11]	Weng Yerui, Fu Aizhen. Investigation of milk HBV DNA in pregnant women with chronic HBV infection [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(3): 457-458.
[12]	Zhan Guoqing, Tan Huabing, Li Fang, et al. Effect of antiviral therapy with entecavir on HBV reactivation in serum HBV DNA negative hepatitis B virus infection-reduced patients with hepatocellular carcinoma receiving transcatheter arterial chemoemholization [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(1): 96-99.
[13]	Xie Xiao, Lu Lungen. Advances in antiviral treatments of HBV-induced liver cirrhosis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(1): 140-144.
[14]	Xiao Yuzhu.. Combination of adefovir dipivoxil and entecavir in treatment of elderly patients with decompensated hepatitis B-induced liver cirrhosis [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2017, 20(5): 546-549.
[15]	Ma Yong.. Prevalence of hepatitis B infection in infants with hepatitis B virus-carrying mothers [J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2017, 20(4): 486-487.