需要不同的抑制剂来克服恩替卡韦耐药性：在回顾性研究中

StephenW

Br J Clin Pharmacol. 2017 May 16. doi: 10.1111/bcp.13330. [Epub ahead of print]
A different inhibitor is required for overcoming entecavir resistance: a comparison of four rescue therapies in a retrospective study.
Yuan G1, Hu C1, Zhou Y2, Liu J1, Huang H1, Li Y1, Yang D2, Zhou F1, Zhang YY3, Zhou Y1.
Author information

1    Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
2    Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
3    HBVtech, Germantown, Maryland, MD, 20874, USA.

Abstract
AIMS:

Little clinical data are available regarding reestablishing the effective inhibition of entecavir (ETV)-resistant mutants. In this retrospective study, we aimed to compare the efficacies of four treatment regimens as rescue therapy for those chronic hepatitis B (CHB) patients with ETV resistance.
METHODS:

A total of 65 patients with ETV resistance were assigned either with tenofovir disoproxil fumarate (TDF) monotherapy (n=21), ETV (0.5 mg) plus adefovir (ADV) combination therapy (n=19), ETV (1.0 mg) monotherapy (n=11) or ETV (0.5 mg) plus TDF combination therapy (n=14). The efficacy and safety of four treatment regimens were compared.
RESULTS:

There were no significant differences among the four study groups in baseline characteristics, including HBV DNA levels (χ2 = 0.749, P=0.862) and hepatitis B e antigen-positivity (χ2 = 0.099, P=0.992). The median reduction in serum HBV DNA level from baseline at week 48 was -2.37±1.07 log10 IU/mL, -2.16±0.81 log10 IU/mL, -1.17±1.23 log10 IU/mL and -2.49±1.10 log10 IU/mL, respectively (F=4.078, P=0.011). The TDF group and ETV (0.5 mg)+TDF group have the highest undetectable HBV DNA rate (76.19% vs. 78.57%) compared to the ETV (0.5 mg)+ADV group and the ETV (1.0 mg) group (63.16% vs. 18.18%, respectively). Two patients in the ETV (1.0 mg) group experienced virological breakthrough at week 48 and was attributed to poor drug adherence.
CONCLUSIONS:

TDF monotherapy appeared to deliver the highest undetectable HBV DNA rate in patients with ETV resistance, and ADV plus ETV combination therapy could be another choice for patients with financial restraint.

This article is protected by copyright. All rights reserved.
KEYWORDS:

Chronic hepatitis B; entecavir; rescue therapy; resistance

PMID:
    28511283
DOI:
    10.1111/bcp.13330

StephenW

Br J Clin Pharmacol。 2017年5月16日。doi：10.1111 / bcp.13330。 [提前印刷]
需要不同的抑制剂来克服恩替卡韦耐药性：在回顾性研究中比较四种救援疗法。
Yuan G1，Hu C1，Zhou Y2，Liu J1，Huang H1，Li Y1，Yang D2，Zhou F1，Zhang YY3，Zhou Y1。
作者信息

1南方医科大学南方医院传染病与肝病科，广州。
2南方医科大学南方医院肝胆外科，广州。
3 HBVtech，Germantown，Maryland，MD，20874，USA。

抽象
目的：

关于重新建立有效抑制恩替卡韦（ETV）抗性突变体的临床资料很少。在这项回顾性研究中，我们旨在比较四种治疗方案对于那些具有耐药性的慢性乙型肝炎（CHB）患者的救援治疗的疗效。
方法：

总共65名患有ETV抗体的患者分别服用替诺福韦地塞普芬富马酸酯（TDF）单药治疗（n = 21），ETV（0.5 mg）加阿德福韦（ADV）联合治疗（n = 19），ETV（1.0 mg）单药治疗n = 11）或ETV（0.5mg）加TDF联合治疗（n = 14）。比较四种治疗方案的疗效和安全性。
结果：

HBV DNA水平（χ2= 0.749，P = 0.862）和乙型肝炎e抗原阳性（χ2= 0.099，P = 0.992），基线特征差异无统计学意义。在第48周，基线血清HBV DNA水平的中值降低为-2.37±1.07log10IU / mL，-2.16±0.81log10IU / mL，-1.17±1.23log10IU / mL和-2.49±1.10log10IU / mL， （F = 4.078，P = 0.011）。与ETV（0.5mg）+ ADV组和ETV（1.0mg）组相比，TDF组和ETV（0.5mg）+ TDF组的HBV DNA检出率（76.19％vs. 78.57％）检出率最高（63.16％vs分别为18.18％）。 ETV（1.0mg）组中的两名患者在第48周经历病毒学突破，并且归因于药物依从性差。
结论：

在ETV耐药患者中，TDF单药治疗似乎达不到最高的HBV DNA检出率，而ADV plus ETV联合治疗可能是财务限制患者的另一选择。

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关键词：

慢性乙型肝炎恩替卡韦;救援治疗抵抗性

结论：
    28511283
DOI：
    10.1111 / bcp.13330