基于替诺福韦的救援治疗对拉米夫定和恩替卡韦耐药的慢性

StephenW

Clin Mol Hepatol. 2017 Jun 30. doi: 10.3350/cmh.2017.0003. [Epub ahead of print]
Efficacy of tenofovir-based rescue therapy for chronic hepatitis B patients with resistance to lamivudine and entecavir.Jeon HJ1, Jung SW1, Park NH1,2, Yang Y1, Noh JH1, Ahn JS1, Kim HR1, Lee JH3, Shin JW1.
Author information
1Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.2Department of Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.3Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.

AbstractBackground/Aims: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks provided a virological response comparable to that of TDF and entecavir (ETV) combination therapy in patients infected with ETV-resistant hepatitis B virus (HBV). Little long-term data in routine clinical practice are available regarding the optimal treatment of patients with ETV-resistant HBV.
Methods: We investigated the long-term antiviral efficacy of combination therapy of TDF+lamivudine (LAM) or TDF+ETV compared to that of TDF monotherapy in 73 patients with resistance to both LAM and ETV.
Results: Patients were treated with TDF monotherapy (n=12), TDF+LAM (n=19), or TDF+ETV (n=42) for more than 6 months. The median duration of TDF-based rescue therapy was 37 months. Virologic response (VR) was found in 63 patients (86.3%). The rates of VR among the three groups (TDF monotherapy, TDF+LAM, and TDF+ETV) were not statistically different (log-rank P=0.200) at 12 months (59.3%, 78.9%, and 51.8%, respectively) or at 24 months (88.4%, 94.7%, and 84.2%). In addition, treatment efficacy of TDF-based combination or TDF monotherapy was not statistically different with ETV-resistant strains or exposure to other antiviral agents. In multivariate analysis, only lower baseline HBV DNA level was an independent predictor for VR (hazard ratio, 0.723; 95% confidence interval, 0.627-0.834; P<0.001).
Conclusions: TDF monotherapy was as effective as combination therapy of TDF+LAM or TDF+ETV in maintaining long-term viral suppression in chronic hepatitis B patients with resistance to both LAM and ETV. HBV DNA level at the start of TDF rescue therapy was the only independent predictor of subsequent VR.


KEYWORDS:  Chronic hepatitis B;  Entecavir;  Lamivudine;  Resistance; Tenofovir

PMID:28669175DOI:10.3350/cmh.2017.0003

StephenW

Clin Mol Hepatol。 2017年6月30日。doi：10.3350 / cmh.2017.0003。 [提前印刷]
基于替诺福韦的救援治疗对拉米夫定和恩替卡韦耐药的慢性乙型肝炎患者的疗效。
Jeon HJ1，Jung SW1，Park NH1,2，Yang Y1，Noh JH1，Ahn JS1，Kim HR1，Lee JH3，Shin JW1。
作者信息

1
    韩国蔚山蔚山医学院蔚山大学医学系内科系。
2
    蔚山大学蔚山大学医学院生物医学研究中心，蔚山，韩国。
3
    韩国蔚山蔚山医学院蔚山大学医学院麻醉与止痛医学系。

抽象
背景/目的：

替诺福韦地索他芬富马酸（TDF）单药治疗48周提供了与耐药性乙型肝炎病毒（HBV）感染患者的TDF和恩替卡韦（ETV）联合治疗相当的病毒学应答。常规临床实践中很少有长期数据可用于患有耐药性乙型肝炎病毒的患者的最佳治疗。
方法：

我们调查了在73例抗LAM和ETV耐药患者中TDF +拉米夫定（LAM）或TDF + ETV组合疗法与TDF单一疗法联合治疗的长期抗病毒疗效。
结果：

患者接受TDF单药治疗（n = 12），TDF + LAM（n = 19）或TDF + ETV（n = 42）治疗6个月以上。基于TDF的救援治疗的中位数为37个月。 63例患者发现病毒学反应（VR）（86.3％）。在12个月时，三组（TDF单药，TDF + LAM和TDF + ETV）的VR差异无统计学意义（对数值P = 0.200）（分别为59.3％，78.9％和51.8％）或24个月（88.4％，94.7％，84.2％）。此外，基于TDF的组合或TDF单一疗法的治疗效果与ETV抗性菌株或暴露于其他抗病毒剂的治疗效果没有统计学差异。在多变量分析中，只有较低的基线HBV DNA水平是VR的独立预测因子（风险比，0.723; 95％置信区间，0.627-0.834; P <0.001）。
结论：

TDF单药治疗与TDF + LAM或TDF + ETV联合治疗对于对LAM和ETV具有抗性的慢性乙型肝炎患者进行长期病毒抑制是有效的。 TDF抢救治疗开始时的HBV DNA水平是后续VR的唯一独立预测因子。
关键词：

慢性乙型肝炎恩替卡韦;拉米夫定;抵抗性;替诺福韦

结论：
    28669175
DOI：
    10.3350 / cmh.2017.0003

StephenW

https://www.e-cmh.org/upload/pdf/cmh-2017-0003.pdf