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标题: 富马酸替诺福韦酯具有抗乙肝病毒耐药株显着疗效 [打印本页]

作者: StephenW    时间: 2015-10-4 10:04     标题: 富马酸替诺福韦酯具有抗乙肝病毒耐药株显着疗效

Tenofovir disoproxil fumarate has a substantial efficacy against multidrug-resistant strains of hepatitis B virus

    Bulent Baran1, Ozlem Mutluay Soyer2, Asli Cifcibasi Ormeci2, Suut Gokturk2, Sami Evirgen2, Filiz Akyuz2, Cetin Karaca2, Kadir Demir2, Fatih Besisik2, Derya Onel3, Mine Gulluoglu4, Selim Badur3 andSabahattin Kaymakoglu2,*

Article first published online: 17 APR 2015

DOI: 10.1111/liv.12831

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Issue
Liver International
Liver International

Volume 35, Issue 10, pages 2265–2274, October 2015

    1    Department of Gastroenterology, Koç University Hospital, Zeytinburnu, Istanbul, Turkey
    2    Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey
    3    Department of Microbiology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey
    4    Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey

* Correspondence
Sabahattin Kaymakoglu, M.D., Professor, Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa 34390, Istanbul, Turkey
Tel: +902124142000 – 31140
Fax: +902126319743
e-mail: [email protected]


Keywords:

    adefovir failure;chronic hepatitis B;genotypic resistance;tenofovir disoproxil fumarate

Abstract
Background & Aims

To evaluate the efficacy of tenofovir in chronic hepatitis B (CHB) patients with adefovir resistance (ADF-R) and suboptimal response to adefovir (ADF-S).
Methods

Nucleos(t)ide analogue (NA)-naïve patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6 months were included in the study. Biochemical and virological tests were obtained at baseline and 3-month intervals in the first year and every 6 months thereafter. The primary outcome measure was complete virological response (CVR) (HBVDNA < 20 IU/ml). CVR rates were calculated by Kaplan–Meier analysis, and a multivariate Cox proportional hazard model was generated to find out factors independently associated with CVR.
Results

A total of 165 patients (118 men, mean age 42 ± 12, 64 HBeAg+) were included in the study. There were 105 patients in NA-naïve, 32 patients in ADF-S and 28 patients in ADF-R groups. All patients in the ADF-R group had multidrug resistance patterns. Mean duration of tenofovir treatment was 29 ± 14 months. CVR rates in NA-naïve, ADF-S and ADF-R groups were 65% vs. 75% vs. 58% at 12th month, 77% vs. 87% vs. 79% at 24th month and 83% vs. 94% vs. 79% at 36th month respectively. According to multivariate Cox regression model, HBeAg positivity (HR = 0.56, 95%CI 0.36–0.86, P = 0.008), high baseline HBVDNA level (HR = 0.64, 95%CI 0.55–0.74, P < 0.001) and ADF-R (HR = 0.47, 95%CI 0.28–0.81, P = 0.006) were independent predictors for CVR. Seven patients encountered mild renal dysfunction and were managed by dose adjustments.
Conclusion

CVR rates during the follow-up show that tenofovir has a decreased, yet still potent in vivo efficacy against multidrug-resistant strains of HBV.


作者: StephenW    时间: 2015-10-4 10:04

富马酸替诺福韦酯具有抗乙肝病毒耐药株显着疗效

    比伦特Baran1,Ozlem Mutluay Soyer2,阿斯利Cifcibasi Ormeci2,Suut Gokturk2,萨米Evirgen2,菲利兹Akyuz2,切廷Karaca2,卡迪尔Demir2,法提赫Besisik2,DERYA Onel3,矿山Gulluoglu4,塞利姆Badur3 andSabahattin Kaymakoglu2,*

文章首次在网上公布:2015年4月17日

DOI:10.1111 / liv.12831

©2015年约翰·威利父子A / S。由John Wiley&Sons出版有限公司

问题
肝国际
肝国际

第35卷,第10期,页2265至2274年,2015年10月

    消化内科,科威特石油公司大学医院,Zeytinburnu,伊斯坦布尔,土耳其1系
    Gastroenterohepatology的2系,医学院,伊斯坦布尔大学,卡帕,伊斯坦布尔,土耳其伊斯坦布尔学院
    微生物学3系,医学院,伊斯坦布尔大学,卡帕,伊斯坦布尔,土耳其伊斯坦布尔学院
    病理4部,医药,伊斯坦布尔大学,卡帕,伊斯坦布尔,土耳其伊斯坦布尔学院

*通讯
Sabahattin Kaymakoglu,医学博士,教授,Gastroenterohepatology系,医学系伊斯坦布尔,伊斯坦布尔大学,卡帕34390,伊斯坦布尔,土耳其
联系电话:902124142000 - 31140
传真:902126319743
电子邮件:[email protected]


关键词:

    阿德福韦衰竭;慢性乙型肝炎;基因型耐药性;富马酸替诺福韦酯

抽象的
背景和目的

为了评估替诺福韦治疗慢性乙型肝炎(CHB)患者阿德福韦耐药(ADF-R)和阿德福韦反应不佳(ADF-S)的疗效。
方法

核苷(酸)的ide类似物(NA)-naïve患者和患者以前阿德福韦失败接收替诺福韦治疗至少6个月的被包括在研究中。生化和病毒学试验是在第一年基线和3个月的间隔和每6个月后获得的。主要的测量结果是完全病毒学应答(CVR)(HBVDNA <20国际单位/毫升)。 CVR率的计算采用Kaplan-Meier分析,并生成一个多元Cox比例风险模型,找出与CVR独立相关因素。
结果

共有165例(118人,平均年龄42±12,64大三阳+)被列入研究。共有105例NA初治,32例在ADF-S和28例患者在ADF-R基团。在ADF-R组所有患者多药耐药性的模式。替诺福韦治疗的平均时间为29±14个月。 CVR率NA-幼稚,ADF-S和ADF-R基团分别为65%对75%对在第12个月58%,77%对87%对在第24个月和83%对94%79%与79在第36个月分别为%。据多元回归模型,e抗原阳性(HR = 0.56,95%CI 0.36-0.86,P = 0.008),高基线HBVDNA水平(HR = 0.64,95%CI 0.55-0.74,P <0.001)和ADF-R (HR = 0.47,95%CI 0.28-0.81,P = 0.006)均对CVR的独立预测因子。七名病人遇到轻度肾功能不全和剂量调整,管理。
结论

在后续节目CVR率替诺福韦已降低,但仍然有效的体内效力针对HBV的多药耐药菌株。




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