添加阿德与恩替对拉米耐药的慢性乙肝炎:2年随访的随机对照

StephenW

http://onlinelibrary.wiley.com/doi/10.1111/liv.12036/abstract
Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study): a 2-year follow-up randomized controlled trial
添加开关阿德福韦与恩替卡韦对拉米夫定耐药的慢性乙型肝炎（ACE研究）：2年随访的随机对照试验
    Hyung Joon Yim1,*,
    Yeon Seok Seo2,
    Eileen L. Yoon1,
    Chang Wook Kim3,
    Chang Don Lee3,
    Sang Hoon Park4,
    Myung Seok Lee4,
    Choong Kee Park5,
    Hee Bok Chae6,
    Moon Young Kim7,
    Soon Koo Baik7,
    Yun Soo Kim8,
    Ju Hyun Kim8,
    Jung Il Lee9,
    Jin Woo Lee9,
    Sun Pyo Hong10,
    Soon Ho Um2,*

Article first published online: 7 JAN 2013

DOI: 10.1111/liv.12036

Abstract
Background

Management of lamivudine-resistant chronic hepatitis B (CHB) remains challenging, as inappropriate choice of treatment may cause multidrug resistance. Until now, randomized trials directly comparing adding adefovir and switching to entecavir monotherapy have not been reported.
Aims

This multicentre prospective randomized study was designed to compare the efficacy of these two strategies.
Methods

Two hundred and nineteen lamivudine-resistant CHB patients were randomized to either adefovir–lamivudine combination group or entecavir monotherapy group (n = 110 vs. 109), and followed up for 24 months.
Results

One hundred and eighty patients completed this study. At month 24, virological response rate [hepatitis B virus (HBV) DNA <60 IU/ml] was higher in the adefovir–lamivudine combination group compared with entecavir group (56.7% vs. 40%, P = 0.025), although biochemical and serological response rates were not significantly different. Genotypic resistance (9.2% vs. 24.6%, P = 0.005) and combined viral breakthrough (2.0% vs. 17.6%, P < 0.001) were more frequent in the entecavir group.

However, by subgroup analysis, virological response rates were not significantly different between the two therapies in HBeAg-positive patients (44.9% vs. 35.7%, P = 0.268) or in patients with high baseline HBV DNA (≥7 log IU/ml) (40.7% vs. 31.3%, P = 0.320) at month 24.
Conclusion

This study showed that adefovir–lamivudine combination provides significantly higher antiviral efficacy and the lower resistance rate compared with the entecavir monotherapy in the management of lamivudine-resistant CHB. However, it had limited efficacy in HBeAg-positive patients or in patients with high baseline HBV DNA.

StephenW

背景

拉米夫定耐药的慢性乙型肝炎（CHB）的管理仍然充满挑战，作为治疗选择不当，可能会导致耐药性。直到现在，直接比较的随机试验添加阿德福韦和切换到恩替卡韦单药治疗没有报道。
目标

这个多中心前瞻性随机对照研究的目的是要比较这两种策略的功效。
方法

一百一十九拉米夫定耐药的慢性乙型肝炎患者被随机分配为阿德福韦酯，拉米夫定联合治疗组或恩替卡韦单药治疗组（N = 110与109），随访期为24个月。
结果

一百八十名患者完成了这项研究。在24个月，病毒学应答率[B型肝炎病毒（HBV）DNA <60 IU /毫升]高阿德福韦酯，拉米夫定联合治疗组与恩替卡韦组（56.7％对40％，P = 0.025）相比，虽然生化血清学反应率分别为不显着的不同。基因型耐药（9.2％比24.6％，P = 0.005）及合并病毒性突破（2.0％对17.6％，P <0.001），恩替卡韦组更频繁。

然而，亚组分析，病毒学应答率没有显着差异的两个治疗HBeAg阳性患者（44.9％比35.7％，P = 0.268）或与高基线HBV DNA（≥7日志IU / ml的患者）在24个月（40.7％对31.3％，P = 0.320）。
结论

这项研究表明，拉米夫定，阿德福韦相结合，提供显着更高的抗病毒疗效和较低的电阻率相比，恩替卡韦单药治疗拉米夫定耐药的慢性乙型肝炎的管理。然而，在HBeAg阳性患者疗效有限，或在患者基线HBV DNA。