富马酸替诺福韦酯（TDF）与在拉米夫定耐药的乙肝TDF /恩曲他

StephenW

J Hepatol. 2016 Aug 18. pii: S0168-8278(16)30440-8. doi: 10.1016/j.jhep.2016.08.008. [Epub ahead of print]
Tenofovir disoproxil fumarate (TDF) versus TDF/emtricitabine (FTC) in lamivudine-resistant hepatitis B: a 5-year randomized study.Fung S1, Kwan P2, Fabri M3, Horban A4, Pelemis M5, Hann HW6, Gurel S7, Caruntu FA8, Flaherty JF9, Massetto B9, Kim K9, Kitrinos KM9, Mani Subramanian G9, McHutchison JG9, Yee LJ9, Elkhashab M10, Berg T11, Sporea I12, Yurdaydin C13, Husa P14, Jablkowsk MS15, Gane E16.
Author information

• 1Department of Medicine, University of Toronto, Canada. Electronic address: [email protected].
• 2Department of Medicine, University of British Columbia, Canada.
• 3Clinic for Infectious Diseases, Medical University of Novi Sad, Serbia.
• 4Department of Adult Infectious Diseases, Medical University of Warsaw, Poland.
• 5Clinic for Infectious and Tropical Diseases, Clinical Centre of Serbia, Serbia.
• 6Department of Medicine, Thomas Jefferson University, USA.
• 7Department of Internal Medicine, Uludag University, Turkey.
• 8National Institute for Infectious Diseases, "Prof Dr Matei Bals", Romania.
• 9Gilead Sciences Inc, Foster City, California, USA.
• 10Toronto Liver Centre, Toronto, Canada.
• 11Clinic of Gastroenterology and Rheumatology, University Hospital Leipzig, Germany.
• 12University of Medicine and Pharmacy, Timisoara, Romania.
• 13Department of Gastroenterology, Ankara University, Turkey.
• 14University Hospital Brno and Faculty of Medicine, Masaryk University Brno, Czech Republic.
• 15Department of Infectious and Liver Diseases, Medical University of Lodz, Poland.
• 16New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand.
  

AbstractBACKGROUND AND AIMS: Long-term treatment with tenofovir disoproxil fumarate (TDF) alone, or in combination with emtricitabine (FTC) is associated with sustained viral suppression in patients with lamivudine resistant (LAM-R) chronic hepatitis B (CHB).
METHODS: LAM-R CHB patients were randomised 1:1 to receive TDF 300 mg or FTC 200 mg and TDF 300 mg once daily in a prospective, double-blind, study. The proportion of patients with plasma hepatitis B virus (HBV) DNA <69 IU/mL (<400 copies/mL) at Week 96 (primary efficacy endpoint) was reported previously. Here we present Week 240 follow-up data.
RESULTS: Overall, 280 patients were randomised to receive TDF (n=141) or FTC/TDF (n=139), and 85.4% completed 240 weeks of treatment. At Week 240, 83.0% of patients in the TDF arm, and 82.7% of patients in the FTC/TDF treatment arm had HBV DNA <69 IU/mL (P=0.96). Rates of normal alanine aminotransferase (ALT) and normalised ALT were similar between groups (P=0.41, P=0.97, respectively). Hepatitis B e antigen loss and seroconversion at Week 240 were similar between groups, (P=0.41, P=0.67, respectively). Overall, six patients achieved hepatitis B surface antigen (HBsAg) loss and one patient (FTC/TDF arm) had HBsAg seroconversion by Week 240. No TDF resistance was observed up to Week 240. Treatment was generally well tolerated, and renal events were mild and infrequent (∼8.6%). The mean change in bone mineral density at Week 240 was -0.98% and -2.54% at the spine and hip, respectively.
CONCLUSIONS: TDF monotherapy was effective and well tolerated in LAM-R CHB patients for up to 240 weeks.
LAY SUMMARY: The goal of oral antiviral treatment for chronic hepatitis B (CHB) is to achieve and maintain undetectable HBV DNA levels. Treatment options with enhanced potency, and low risk of resistance development for patients infected with lamivudine resistant (LAM-R) HBV are required. Tenofovir disoproxil fumarate (TDF) monotherapy was effective and well tolerated without TDF resistance development in CHB patients with LAM-R, for up to 240 weeks.
Copyright © 2016. Published by Elsevier B.V.


KEYWORDS: Bone mineral density; Emtricitabine; Lamivudine resistant; Renal function; Tenofovir disoproxil fumarate; Viral suppression

PMID:27545497DOI:10.1016/j.jhep.2016.08.008

StephenW

肝脏病学杂志。 2016年18月PII：S0168-8278（16）30440-8。 DOI：10.1016 / j.jhep.2016.08.008。 [打印EPUB提前]
富马酸替诺福韦酯（TDF）与在拉米夫定耐药的乙肝TDF /恩曲他滨（FTC）：5年的随机研究。
丰S1，关P2，法布里M3，Horban A4，Pelemis M5，汉恩HW6，居雷尔S7，Caruntu FA8，弗莱厄蒂JF9，马赛托B9，金K9，Kitrinos KM9，玛尼萨勃拉曼尼亚G9，McHutchison JG9，怡LJ9，Elkhashab M10，伯格T11，Sporea I12，Yurdaydin C13，P14户撒，Jablkowsk MS15，甘恩E16。
作者信息

    医学教研室，加拿大多伦多大学。电子地址：[email protected]。
    医学教研室，加拿大不列颠哥伦比亚大学。
    3Clinic传染病，医科大学诺维萨德，塞尔维亚。
    成人传染病4Department，波兰华沙医科大学。
    5Clinic传染病和热带病，塞尔维亚，塞尔维亚临床中心。
    医药，托马斯·杰斐逊大学，美国的6Department。
    内科，乌鲁达大学，土耳其7Department。
    8National研究所传染病，“教授博士马太的Bals”，罗马尼亚。
    9Gilead科学公司，福斯特市，美国加利福尼亚州。
    10Toronto肝脏中心，加拿大多伦多。
    胃肠病学和风湿病，大学医院德国莱比锡11Clinic。
    医药，蒂米什瓦拉，罗马尼亚12University。
    消化内科，安卡拉大学，土耳其13Department。
    14University医院布尔诺医学院，马萨里克大学布尔诺，捷克共和国。
    传染病和肝病15Department，波兰罗兹医科大学。
    16New新西兰肝脏移植单位，奥克兰市医院，新西兰奥克兰。

抽象
背景和目的：

与富马酸替诺福韦酯（TDF）单独，或与恩曲他滨（FTC）组合长期治疗与患者拉米夫定耐药（LAM-R），慢性乙型肝炎（CHB）的持续的病毒抑制相关联。
方法：

LAM-R CHB患者被随机分为1：1在一项前瞻性，双盲，研究每天一次接受TDF 300毫克或200 FTC mg和TDF 300毫克。患者血浆乙型肝炎病毒（HBV）DNA <69国际单位/毫升，在96周（主要疗效终点）（<400拷贝/ mL）的比例为以前的报告。这里，我们现在240周的随访数据。
结果：

总体而言，280例患者随机接受TDF（N = 141），或FTC / TDF（N = 139），和85.4％，完成240周治疗。在240周的患者在TDF手臂83.0％，而患者在FTC / TDF治疗组82.7％的患者HBV DNA <69 IU /毫升（P = 0.96）。正常的谷丙转氨酶（ALT）和归ALT率（分别为P = 0.41，P = 0.97），两组相似。在240周的乙肝e抗原损失和血清学转换（分别为P = 0.41，P = 0.67）显群体之间相似。总体而言，名患者实现乙肝表面抗原（HBsAg）的损失和1例（FTC / TDF手臂）有乙肝表面抗原血清学转换乘240周观察到240周的治疗没有TDF电阻一般耐受性良好，与肾事件是轻和偶发（~8.6％）。在240周骨密度的平均变化为-0.98％，并分别在脊柱和髋部，-2.54％。
结论：

TDF单一治疗是有效的，在LAM-R慢性乙型肝炎患者的耐受性良好长达240周。
LAY摘要：

口服抗病毒治疗慢性乙型肝炎（CHB）的目标是实现和保持检测不到的HBV DNA水平。必须增强效力，并为感染拉米夫定耐药（LAM-R）HBV耐药的患者发展低风险的治疗方案。富马酸替诺福韦酯（TDF）单药治疗是有效的，没有TDF抗性发展良好的耐受性慢性乙型肝炎患者LAM-R，长达240周。

版权所有©2016年出版由Elsevier B.V.
关键词：

骨密度;恩曲他滨;拉米夫定耐药;肾功能;富马酸替诺福韦酯;抑制病毒

结论：
    27545497
DOI：
    10.1016 / j.jhep.2016.08.008