富马酸替诺福韦酯在亚洲或太平洋岛民慢性乙型肝炎患者高

StephenW

Tenofovir Disoproxil Fumarate in Asian or Pacific Islander Chronic Hepatitis B Patients With High Viral Load (≥ 9 log10 copies/mL)

    Scott Fung1,*,
    Stuart C. Gordon2,
    Zahary Krastev3,
    Andrzej Horban4,
    Jörg Petersen5,
    Jan Sperl6,
    Edward Gane7,
    Ira M. Jacobson8,
    Leland J. Yee9,
    Phillip Dinh9,
    Eduardo B. Martins9,
    John F. Flaherty9,
    Kathryn M. Kitrinos9,
    Geoffrey Dusheiko10,
    Huy Trinh11,
    Robert Flisiak12,
    Vinod K. Rustgi13,
    Maria Buti14 and
    Patrick Marcellin15

DOI: 10.1111/liv.12694

This article is protected by copyright. All rights reserved.

Author InformationPublication History
Author Information

    1    University of Toronto, Ontario, Canada
    2    Henry Ford Health System, Detroit, MI, USA
    3    University Hospital, St. Ivan Rilsky, Sofia Bulgaria
    4    Warsaw Medical University, Warsaw, Poland
    5    Liver Unit Asklepios Klinik St. Georg, Hamburg, Germany
    6    Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    7    Auckland City Hospital, Aukland, New Zealand
    8    Weill Cornell Medical College, New York, NY, USA
    9    Gilead Sciences, Inc., Foster City, CA, USA
    10    Royal Free Hospital, London, United Kingdom
    11    San Jose Gastroenterology, San Jose, CA, USA
    12    Medical University of Bialystok, Bialystok, Poland
    13    Metropolitan Liver Diseases, Fairfax, VA, USA
    14    Hospital General Universitari Vall d'Hebron and Ciberehd del Instituto Carlos III, Barcelona, Catalonia, Spain
    15    Hôpital Beaujon, University of Paris, Clichy, France

* Address correspondence to:
Scott Fung, MD, FRCPC
Address: 200 Elizabeth St., 9N-981
Toronto General Hospital
University Health Network
Toronto, ON Canada
M5G 2C4
Phone: (416) 340-3893
Fax: (416) 340-3258
Email: [email protected]

    This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.12694


Abstract
Background & Aims

We evaluated the antiviral response of Asian or Pacific Islander (API) patients with chronic hepatitis B (CHB) who had baseline high viral load (HVL), defined as pre-treatment hepatitis B virus (HBV) DNA ≥9 log10 copies/mL, following up to 288 weeks of tenofovir disoproxil fumarate (TDF) treatment.
Methods

A total of 205 HBeAg-negative and HBeAg-positive self-described API patients were randomized to receive 48 weeks of TDF 300 mg (HVL n=18) or adefovir dipivoxil 10 mg (HVL n=15) in a blinded fashion, followed by open-label TDF for an additional 240 weeks. The proportions of HVL versus non-HVL patients with HBV DNA <400 copies/mL were compared. Mean declines in HBV DNA were evaluated in API versus non-API patients.
Results

Throughout the first 72 weeks of treatment, a smaller proportion of HVL API patients reached HBV DNA <400 copies/mL than non-HVL API patients. However, after this timepoint similar proportions of HVL and non-HVL API patients achieved HBV DNA <400 copies/mL (100% versus 97%, respectively), which was maintained through week 288, where 92% of HVL patients and 99% of non-HVL API patients on treatment had HBV DNA <400 copies/mL. During the 288 weeks of treatment, API patients had similar mean HBV DNA declines as non-API patients, regardless of whether patients were HVL or non-HVL. No API HVL patient had persistent viremia at week 288. No resistance was detected among HVL or non-HVL patients.
Conclusions

API patients with HVL CHB achieve HBV DNA <400 copies/mL with long-term TDF treatment; however, achieving viral suppression may take longer for HVL patients relative to non-HVL API patients.

StephenW

富马酸替诺福韦酯在亚洲或太平洋岛民慢性乙型肝炎患者高病毒载量（≥9 log10拷贝/毫升）

    斯科特Fung1，*，
    斯图尔特C. Gordon2，
    Zahary Krastev3，
    安杰Horban4，
    约尔格Petersen5，
    一月Sperl6，
    爱德华Gane7，
    艾拉米Jacobson8，
    利兰·J·Yee9，
    菲利普Dinh9，
    爱德华B. Martins9，
    约翰·Flaherty9，
    凯瑟琳M. Kitrinos9，
    杰弗里Dusheiko10，
    伊Trinh11，
    罗伯特Flisiak12，
    维诺德K. Rustgi13，
    玛丽亚Buti14和
    帕特里克Marcellin15

DOI：10.1111/ liv.12694

这篇文章是受版权保护的。版权所有。

作者InformationPublication历史
作者信息

    多伦多，安大略省，加拿大的大学1
    2亨利福特健康系统，底特律，密歇根州，美国
    3大学医院，圣伊万Rilsky，保加利亚索非亚
    4华沙医学大学，波兰华沙
    5肝单位阿斯科勒比俄斯KLINIK圣乔治，汉堡，德国
    6研究院临床和实验医学杂志，布拉格，捷克共和国
    7奥克兰市医院，奥克兰，新西兰
    8威尔康乃尔医学院，纽约州，纽约州，美国
    9吉利德科学公司，福斯特市，加利福尼亚，美国
    10皇家自由医院，伦敦，英国
    11圣荷西消化内科，圣荷西，加州，美国
    比亚韦斯托克，比亚韦斯托克，波兰12医科大学
    13大都会肝病，费尔法克斯，弗吉尼亚州，美国
    14医院一般Universitari瓦尔德希伯伦和Ciberehd德尔研究所卡洛斯三世，巴塞罗那，加泰罗尼亚，西班牙
    15 HOPITAL Beaujon，巴黎大学，克利希，法国

*通讯地址：
斯科特丰，医学博士，FRCPC
地址：200伊丽莎白街，9N-981
多伦多综合医院
大学健康网络
多伦多，加拿大
M5G2C4
电话：（416）340-3893
传真：（416）340-3258
电子邮件：[email protected]

    本文已被接受发表，并经过充分的同行评审，但通过审稿，排版，分页和校对过程，这可能会导致这个版本和记录的版本之间的差异一直没有。请引用本文为DOI：10.1111/ liv.12694


摘要
背景与目的

我们评估的抗病毒反应亚裔或太平洋岛民（API），慢性乙型肝炎（CHB）谁了基线高病毒载量（HVL），定义为治疗前乙肝病毒（HBV）的DNA≥9log10拷贝/毫升，下面高达288周富马酸替诺福韦酯（TDF）治疗。
方法

总共有205例HBeAg阴性和HBeAg阳性的自我描述API的患者随机接受48周的TDF300毫克（HVL N =18）或阿德福韦酯10毫克（HVL N =15），采用盲法，其次是开放标签TDF为增加240个星期。 HVL的与非HVL患者的HBV DNA的比例<400拷贝/毫升进行比较。乙肝病毒DNA的平均跌幅的API与非API患者进行了评价。
结果

纵观前72周的治疗，HVL API的患者比例较小达到HBV DNA<400拷贝/毫升比非HVL API的患者。但是，此时间点后HVL取得HBV DNA<400拷贝/ ml（100％和97％，分别）非HVL API的患者，这是通过288周保持，类似的比例，其中92％HVL患者和99％的非HVL API的患者的治疗有乙型肝炎病毒DNA<400拷贝/毫升。在288周的治疗，患者的API也有类似的平均血清HBV DNA下降的非API患者，无论患者是否HVL或非HVL。没有API HVL病人有持续性的病毒血症，在288周无阻力之间HVL或非HVL患者进行检测。
结论

API患者HVL CHB达到HBV DNA<400拷贝/ mL的长期TDF治疗;然而，实现抑制病毒可能需要较长的时间相对于非HVL API患者HVL患者。