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Volume 37 Issue 5
May  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(5): 1053-1058

Antiviral effect of entecavir in chronic hepatitis B patients with rtA181V/T mutation

DOI: 10.3969/j.issn.1001-5256.2021.05.016

  • Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, China

  • Received Date: 2020-10-14
  • Accepted Date: 2020-11-20
  • Published Date: 2021-05-20
    Abstract
  •   Objective  To investigate the clinical effect of entecavir (ETV) rescue treatment in chronic hepatitis B (CHB) patients at the onset of rtA181V/T mutation.  Methods  A total of 174 CHB patients who were treated in the outpatient and inpatient departments of The Affiliated Hospital of Xuzhou Medical University from January 2012 to January 2017 and underwent the detection of drug-resistance mutations of the genes in the reverse transcription (RT) polymerase region were enrolled, among whom there were 72 previously untreated patients and 102 treatment-experienced patients with virological breakthrough or poor response. The association between the previous medication history of nucleos(t)ide analogues and the mutation pattern (including rtA181V/T) was evaluated in the treatment-experienced CHB patients. A total of 155 patients were enrolled, among whom 72 patients had no drug-resistance mutations, 45 had rtA181V/T mutation, and 38 had rtA181V/T+rtN236T mutation. The three groups were compared in terms of virologic response and biochemical parameters at baseline and at weeks 24 and 48 of ETV rescue treatment. The t-test was used for comparison of normally distributed continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups; the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between two groups. A logistic regression analysis was used to screen out the influencing factors for poor prognosis.  Results  A analysis of the previous medication history of NAs and the mutation patterns for all patients suggested that the patients with the medication history of multiple NAs tended to have multisite mutations and multi-drug resistance (χ2=4.295, P < 0.05). The level of HBV DNA at the time of virological breakthrough was lower than that at the time of initial administration of NAs in the rtA181V/T mutation group [(6.22±1.48) log10 IU/ml vs (7.08±1.59) log10 IU/ml, t=3.098, P=0.002] and the rtA181V/T+rtN236T mutation group [(5.94±1.45) log10 IU/ml vs (6.94±1.61) log10 IU/ml, t=2.850, P=0.004]. At week 48 of ETV rescue treatment, there were no significant differences between the three groups in HBV DNA negative conversion rate (83.3% vs 82.2% vs 81.6%, P > 0.05) and HBeAg negative conversion rate (22.2% vs 17.8% vs 21.1%, P > 0.05), and there were also no significant differences in alanine aminotransferase normalization rate (77.1% vs 85.2% vs 83.3%, P > 0.05), aspartate aminotransferase normalization rate (80.4% vs 75.9% vs 76.0%, P > 0.05), and total bilirubin normalization rate (80.8% vs 79.3% vs 78.1%, P > 0.05). HBV DNA level at the beginning of ETV treatment was the risk factor for the treatment outcome of 48-week antiviral therapy (odds ratio = 1.655, 95% confidence interval: 1.128-2.428, P=0.01).  Conclusion  ETV has a good antiviral effect in treatment-experienced CHB patients with rtA181 drug-resistance mutation, and HBV DNA level at the initiation of ETV treatment can predict the outcome of 48-week ETV rescue treatment.

     

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    • References(26)
  • [1]
    OTT JJ, STEVENS GA, GROEGER J, et al. Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity[J]. Vaccine, 2012, 30(12): 2212-2219. DOI: 10.1016/j.vaccine.2011.12.116.
    [2]
    ILOEJE UH, YANG HI, SU J, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load[J]. Gastroenterology, 2006, 130(3): 678-686. DOI: 10.1053/j.gastro.2005.11.016.
    [3]
    KIM GA, LIM YS, HAN S, et al. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B[J]. Gut, 2018, 67(5): 945-952. DOI: 10.1136/gutjnl-2017-314904.
    [4]
    WANG H, GUO ZG. Study on HBV pre-C region A1896 gene mutation and clinical drug[J]. J Changchun Univ Chin Med, 2019, 35(1): 144-146. DOI: 10.13463/j.cnki.cczyy.2019.01.042.

    王涵, 郭志钢. HBV前C区A1896基因突变的探讨及临床用药研究[J]. 长春中医药大学学报, 2019, 35(1): 144-146. DOI: 10.13463/j.cnki.cczyy.2019.01.042.
    [5]
    Expert Committee on Hepatitis B Virus Resistance. Expert consensus on hepatitis B virus resistance[J/CD]. Chin J Exp Clin Infect Dis(Electronic Edition), 2008, 2(1): 90-98. DOI: 10.3969/j.issn.1674-1358.2008.01.018.

    乙型肝炎病毒耐药专家委员会. 乙型肝炎病毒耐药专家共识[J/CD]. 中华实验和临床感染病杂志(电子版), 2008, 2(1): 90-98. DOI: 10.3969/j.issn.1674-1358.2008.01.018.
    [6]
    ZOULIM F, LOCARNINI S. Management of treatment failure in chronic hepatitis B[J]. J Hepatol, 2012, 56 Suppl 1: s112-s122. DOI: 10.1016/S0168-8278(12)60012-9.
    [7]
    YEON JE, YOO W, HONG SP, et al. Resistance to adefovir dipivoxil in lamivudine resistant chronic hepatitis B patients treated with adefovir dipivoxil[J]. Gut, 2006, 55(10): 1488-1495. DOI: 10.1136/gut.2005.077099.
    [8]
    WARNER N, LOCARNINI S. The antiviral drug selected hepatitis B virus rtA181T/sW172* mutant has a dominant negative secretion defect and alters the typical profile of viral rebound[J]. Hepatology, 2008, 48(1): 88-98. DOI: 10.1002/hep.22295.
    [9]
    LIU Y, MILLER MD, KITRINOS KM. HBV clinical isolates expressing adefovir resistance mutations show similar tenofovir susceptibilities across genotypes B, C and D[J]. Liver Int, 2014, 34(7): 1025-1032. DOI: 10.1111/liv.12343.
    [10]
    European Association For The Study Of The Liver. EASL olinical practice guidelines: Management of chronic hepatitis B[J]. J Hepatol, 2009, 50(2): 227-242. DOI: 10.1016/j.jhep.2008.10.001.
    [11]
    Chinese Medical Association Infectious Diseases Branch, Chinese Medical Association Hepatology Branch. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clin Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.

    中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
    [12]
    Chinese Medical Association Infectious Diseases Branch, Chinese Medical Association Hepatology Branch. Guidelines for the prevention and treatment of chronic hepatitis B (version 2015)[J]. J Clin Hepatol, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.

    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(2015年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.
    [13]
    YEH CT, CHIEN RN, CHU CM, et al. Clearance of the original hepatitis B virus YMDD-motif mutants with emergence of distinct lamivudine-resistant mutants during prolonged lamivudine therapy[J]. Hepatology, 2000, 31(6): 1318-1326. DOI: 10.1053/jhep.2000.7296.
    [14]
    VILLET S, PICHOUD C, BILLIOUD G, et al. Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure[J]. J Hepatol, 2008, 48(5): 747-755. DOI: 10.1016/j.jhep.2008.01.027.
    [15]
    SUN MS, WANG GQ, ZHANG W, et al. The current status of lamivudine-treated patients with chronic hepatitis B[J]. Chin Prevent Med, 2012, 13(1): 18-22. (in Chinese) https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYC201201006.htm

    孙秘书, 王贵强, 张伟, 等. 拉米夫定经治慢性乙型肝炎患者治疗现状调查分析[J]. 中国预防医学杂志, 2012, 13(1): 18-22. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYC201201006.htm
    [16]
    GAI HP, SUN WX, YUAN DS, et al. The clinical implications of pre-existing drug resistance to nucleo(t)ide analogues-based antiviral therapy[J]. J Clin Hepatol, 2012, 28(11): 841-844. http://lcgdbzz.org/article/id/LCGD201211017

    盖洪鹏, 孙伟翔, 袁德胜, 等. 预存耐药对核苷(酸)类似物抗病毒治疗应答和耐药的影响[J]. 临床肝胆病杂志, 2012, 28(11): 841-844. http://lcgdbzz.org/article/id/LCGD201211017
    [17]
    AHN SH, PARK YK, PARK ES, 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]. J Virol, 2014, 88(12): 6805-6818. DOI: 10.1128/JVI.00635-14.
    [18]
    JI FZ, WANG L, YANG BH, et al. Clinical characteristics and effect of secondary individualized therapy in chronic hepatitis B patients infected with rtA181 mutation hepatitis B virus[J]. Chin J Hepatol, 2012, 20(4): 280-284. DOI: 10.3760/cma.j.issn.1007-3418.2012.04.011.

    姬粉芝, 王磊, 杨保华, 等. rtA181位点突变乙型肝炎病毒感染患者的临床特点及个体化再治疗效果[J]. 中华肝脏病杂志, 2012, 20(4): 280-284. DOI: 10.3760/cma.j.issn.1007-3418.2012.04.011.
    [19]
    CHANG TT, LIAW YF, WU SS, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B[J]. Hepatology, 2010, 52(3): 886-893. DOI: 10.1002/hep.23785.
    [20]
    HAN DG, WU SF. Efficacy comparison of entecavir alone and combined with adefovir dipivoxil in the treatment of patients with rtA181V/T mutation hepatitis B[J]. J Pract Med, 2018, 34(16): 2811-2812, 2815. DOI: 10.3969/j.issn.1006-5725.2018.16.044.

    韩登高, 吴韶飞. 恩替卡韦单用与联合阿德福韦酯治疗rtA181V/T突变乙肝患者的疗效对比[J]. 实用医学杂志, 2018, 34(16): 2811-2812, 2815. DOI: 10.3969/j.issn.1006-5725.2018.16.044.
    [21]
    LUO J, LI X, WU Y, et al. Efficacy of entecavir treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B patients in real life[J]. Int J Med Sci, 2013, 10(4): 427-433. DOI: 10.7150/ijms.5472.
    [22]
    LU T, LI CZ. Rescue therapy of tenofovir disoproxil fumarate in hepatitis B patients with nucleoside/nucleotide analogue resistant[J]. J Prac Hepatol, 2016, 19(3): 369-372. DOI: 10.3969/j.issn.1672-5069.2016.03.032.
    [23]
    LIM YS, YOO BC, BYUN KS, et al. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in adefovir-resistant chronic hepatitis B patients with multiple drug failure: Results of a randomised trial[J]. Gut, 2016, 65(6): 1042-1051. DOI: 10.1136/gutjnl-2014-308435.
    [24]
    BERG T, MARCELLIN P, ZOULIM F, et al. Tenofovir is effective alone or with emtricitabine in adefovir-treated patients with chronic-hepatitis B virus infection[J]. Gastroenterology, 2010, 139(4): 1207-1217. DOI: 10.1053/j.gastro.2010.06.053.
    [25]
    FUNG S, KWAN P, FABRI M, et al. Randomized comparison of tenofovir disoproxil fumarate vs emtricitabine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis B[J]. Gastroenterology, 2014, 146(4): 980-988. DOI: 10.1053/j.gastro.2013.12.028.
    [26]
    LI P, GENG J, LI W, et al. Antiviral efficacy of entecavir for hepatitis B virus rtA181V/T mutants[J]. Virol J, 2017, 14(1): 68. DOI: 10.1186/s12985-017-0739-z.
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