104周的疗效和安全性根据替比夫定优化策略：一项随机，对

StephenW

104-week efficacy and safety of telbivudine based optimization strategy in chronic hepatitis B patients: A randomized, controlled study

    Jian Sun 1,
    Qing Xie 2,
    Deming Tan 3,
    Qin Ning 4,
    Junqi Niu 5,
    Xuefan Bai 6,
    Rong Fan 1,
    Shijun Chen 7,
    Jun Cheng 8,
    Yanyan Yu 9,
    Hao Wang 10,
    Min Xu 11,
    Guangfeng Shi 12,
    Mobin Wan 13,
    Xinyue Chen 14,
    Hong Tang 15,
    Jifang Sheng 16,
    Xiaoguang Dou 17,
    Junping Shi 18,
    Hong Ren 19,
    Maorong Wang 20,
    Hongfei Zhang 21,
    Zhiliang Gao 22,
    Chengwei Chen 23,
    Hong Ma 24,
    Jidong Jia 24,
    Jinlin Hou 1,*

DOI: 10.1002/hep.26885

Copyright © 2013 American Association for the Study of Liver Diseases


    1

    Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou
    2

    Department of Infectious Diseases, Ruijin Hospital, Shanghai
    3

    Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha
    4

    Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
    5

    Hepatology Unit, No. 1 Hospital affiliated to Jilin University, Changchun
    6

    Department of Infectious Diseases, Tangdu Hospital, Xi'an
    7

    Ji'nan Infectious Diseases Hospital, Ji'nan
    8

    Beijing Ditan Hospital, Beijing
    9

    Department of Infectious Diseases, First Hospital of Peking University, Beijing
    10

    Hepatology Unit, Peking University People's Hospital, Beijing
    11

    8th People's Hospital, Guangzhou
    12

    Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai
    13

    Department of Infectious Diseases, Changhai Hospital, Shanghai
    14

    Beijing Youan Hospital, Beijing
    15

    Department of Infectious Diseases, West China Hospital, Chengdu
    16

    Department of Infectious Diseases, Zhejiang University 1st Affiliated Hospital, Hangzhou
    17

    Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang
    18

    6th People's Hospital, Hangzhou
    19

    Department of Infectious Diseases, The second Affiliated Hospital, Chongqing Medical University, Chongqing
    20

    Department of Infectious Diseases, 81st PLA Hospital, Nanjing
    21

    302nd PLA Hospital, Beijing
    22

    Department of Infectious Diseases, Sun Yat-Sen University 3rd Affiliated Hospital, Guangzhou
    23

    Department of Infectious Diseases, 85th PLA Hospital, Shanghai
    24

    Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China

*Correspondence: Jinlin Hou, Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China Tel: 00862061641941 Fax: 00862087719653 Email: [email protected]



Abstract

Optimization strategy based on ROADMAP concept is supposed to improve the clinical outcomes of patients with suboptimal antiviral response. The aim of this study is to prove the concept with a multicenter, open-label, randomized, controlled study. Six hundred and six Hepatitis B e antigen (HBeAg) -positive, nucleos(t)ide -naive chronic hepatitis B patients were randomized to OPTIMIZE or MONO group. Patients in OPTIMIZE group were treated with telbivudine for 24 weeks, after which those suboptimal responders with HBV DNA ≥ 300 copies/mL at week 24 received telbivudine plus adefovir until week 104, while the early virological responders continued telbivudine monotherapy. Patients in MONO group received telbivudine monotherapy. All patients with telbivudine monotherapy were added on adefovir if viral breakthrough developed. Sixty eight percent (204/300) patients in OPTIMIZE group were added on adefovir due to suboptimal response. At week 104, compared to MONO group, more patients in OPTIMIZE group achieved HBV DNA < 300 copies/ml (76.7% vs. 61.2%, p<0.001) with less genotypic resistance (2.7% vs. 25.8%, p<0.001). The rates of HBeAg seroconversion and ALT normalization were comparable between two groups (23.7% vs. 22.1%; 80.7% vs. 79.2%). For week 24 suboptimal responders, telbivudine plus adefovir showed additive antiviral potency with 71.1% achieving virological response at week 104 and only 0.5% developing genotypic resistance, compared with 46.6% who achieved virological response and 37.8% who developed genotypic resistance with telbivudine monotherapy. Both treatment regimens were well tolerated with observed persistent increase of glomerular filtration rate. Conclusion: For suboptimal virological responders to telbivudine at week 24, adjusting treatment strategy is recommended. Adding on adefovir can benefit these patients with additive antiviral potency and low resistance without increased side effect. (Hepatology 2013;)

StephenW

104周的疗效和慢性乙肝患者根据替比夫定优化策略安全性：一项随机，对照研究

    孙立坚1 ，
    清泄2 ，
    戴明谭3 ，
    宁琴4 ，
    牛俊奇5 ，
    金学范白6 ，
    戎垡嗯1 ，
    使君陈7 ，
    郡城8 ，
    岩岩瑜9 ，
    王浩10 ，
    许敏11 ，
    广丰石12 ，
    漠滨13万，
    陈新月14 ，
    唐虹15 ，
    继芳盛16 ，
    晓光豆17 ，
    军平石18 ，
    弘仁19 ，
    茂荣王20 ，
    鸿飞21张，
    高志良22 ，
    程炜陈23 ，
    宏马24 ，
    冀东佳24 ，
    金麟侯1 ， *

DOI ： 10.1002/hep.26885

版权所有©肝病研究2013美国协会


    1

    肝病单位，南方医科大学南方医院，南方医科大学，广州
    2

    感染科，瑞金医院，上海
    3

    传染病中南大学湘雅医院，湖南长沙
    4

    部和传染病，同济医院，同济医学院，华中科技大学，武汉研究所
    5

    肝病单位， 1号附属医院吉林大学，长春
    6

    感染科，唐都医院，西安
    7

    济南市传染病医院，济南
    8

    北京地坛医院，北京
    9

    传染科，北京大学第一医院
    10

    肝脏病学组，北京大学人民医院，北京
    11

    第八人民医院，广州市
    12

    传染病复旦大学附属华山医院，上海
    13

    感染科，长海医院，上海
    14

    北京佑安医院，北京
    15

    传染科，中国西部医院，成都
    16

    传染病，浙江大学第一附属医院，杭州科
    17

    感染科，中国医科大学，沉阳盛京医院
    18

    第六人民医院，杭州
    19

    传染科，第二附属医院，重庆医科大学，重庆
    20

    传染科，解放军第81医院，南京
    21

    解放军第302医院，北京
    22

    感染科，中山大学大学第三附属医院，广州
    23

    传染科，解放军第85医院，上海
    24

    肝病研究中心，北京友谊医院，首都医科大学，北京，中国

*通讯作者：侯锦麟，肝病单位，南方医科大学南方医院，南方医科大学，广州， 510515 ，中国电话： 00862061641941传真： 00862087719653电子邮件： [email protected]



摘要

根据路线图的概念优化策略应该是改善患者最理想的抗病毒反应的临床结果。本研究的目的是要证明一个多中心，开放标签，随机，对照研究的概念。六百六乙型肝炎e抗原（HBeAg ）阳性，核苷（酸） IDE -天真慢性乙型肝炎患者随机优化或单声道组。在OPTIMIZE组患者替比夫定治疗24周，之后，这些次优反应与HBV DNA ≥ 300拷贝/毫升在24周接受替比夫定，加上阿德福韦至104周，而早期病毒学应答替比夫定继续单药治疗。在MONO组患者接受替比夫定单药治疗。所有患者替比夫定与单药治疗增加了对阿德福韦，如果病毒突破发展。率68％ （204 /300）的患者在OPTIMIZE组增加了对阿德福韦因疗效欠佳。在104周，相较于单声道组，更多的患者在最佳化集团实现HBV DNA < 300拷贝/ ml （ 76.7 ％比61.2 ％ ， P <0.001 ），以较少的基因型耐药（ 2.7 ％对25.8 ％ ， P <0.001 ） 。 HBeAg血清学转换，ALT复常率分别为可比两个组（ 23.7 ％对22.1 ％， 80.7 ％和79.2 ％ ）之间。对于一周24次优反应，替比夫定加阿德福韦表明添加剂的抗病毒效力有71.1 ％达到病毒学应答在本周104和只有0.5 ％发展基因型耐药，与谁取得病毒学应答和37.8 ％谁开发基因型耐药与单药替比夫定46.6 ％相比。这两种治疗方案均能很好耐受，肾小球滤过率的观察持续上升。结论：对于不理想的病毒学应答替比夫定24周时，调整治疗策略建议。增加对阿德福韦可以享受这些患者添加剂抗病毒能力和低电阻不增加副作用。 （肝脏病学2013 ;)