Association of Lamivudine-Resistant Mutational Patterns With the Antiviral Effect of Adefovir in Patients With Chronic Hepatitis B
Association of Lamivudine-Resistant Mutational Patterns With the Antiviral Effect of Adefovir in Patients With Chronic Hepatitis B
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DOI：
10.1002/jmv.21402
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发表时间：
2009-03-01
影响因子：
12.7
通讯作者：
Yoo, Wang Don
中科院分区：
文献类型：
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作者：
Cha, Choong Keun;Kwon, Hyeok Choon;Yoo, Wang Don
阿德福韦具有强大的抗病毒活性，可用于抢救拉米夫定耐药菌株。本研究的目的是评估拉米夫定耐药慢性乙型肝炎患者拉米夫定耐药突变的模式及其对阿德福韦抢救治疗的病毒学应答的影响。基线血样通过限制性片段质量多态性分析拉米夫定耐药突变。评估病毒学反应、ALT复常率和HBeAg丢失。用实时定量聚合酶链式反应检测阿德福韦治疗前和治疗24周时的血清HBVDNA水平。在67例慢性乙型肝炎患者中，65例(97%)存在YMDD基序拉米夫定耐药突变[27例(41%)rtM2041，22例(34%)rtM204V，16例(25%)rtM2041/V]。除YMDD突变外，rtL180M、rtL801和rtV173L突变分别存在于78%、43%和11%的患者中。RtM204V突变总是伴随rtL180M，rtL801与rtM2041一起出现。携带rtM2041和rtM204V突变株的患者在24周时血清乙肝病毒的平均降幅无差异(分别为-3.3log10拷贝/ml和-3.3log10拷贝/ml；P=0.303)。在阿德福韦给药期间，rtL180M、rtL801和rtV173L的存在并没有显著影响病毒载量的降低。这些结果表明，rtL801突变体与rtM2041共同选择作为补偿突变，与rtL180M与rtM204V共同选择作为补偿突变，并且阿德福韦对所有评价的拉米夫定耐药乙肝病毒突变模式显示出类似的抗病毒效果。J.Med.维罗尔。81：417-424,2009。(C)2009年Wiley-Liss，Inc.
Adefovir has a potent antiviral activity as a rescue treatment against lamivudine-resistant strains. The aim of this study was to assess the patterns of lamivudine-resistant mutations and their influence on the virologic response to adefovir rescue therapy in patients with lamivudine-resistant chronic hepatitis B. Sixty-seven patients with lamivudine-resistant chronic hepatitis B were treated with adefovir monotherapy. Baseline blood samples were analyzed for lamivudine-resistant mutations via restriction fragment mass polymorphism. Virologic responses, ALT normalization and loss of HBeAg were assessed. Serum HBV DNA levels were measured using real-time PCR at baseline and 24 weeks of adefovir therapy. Of the 67 patients with chronic hepatitis B, 65 patients (97%) had lamivudine-resistant mutations in the YMDD motif [27 (41%) rtM2041, 22 (34%) rtM204V, and 16 (25%) rtM2041/V]. In addition to the YMDD mutations, the rtL180M, rtL801, and rtV173L mutations were also present in 78%, 43%, and 11% of patients, respectively. The rtM204V mutation always accompanied rtL180M, and rtL801 was always observed in conjunction with rtM2041. Decrease in mean serum HBV did not differ between patients carrying the rtM2041 versus rtM204V mutant at week 24 (-3.3 vs. -3.3 log 10 copies/ml, respectively; P = 0.303). The presence of the rtL180M, rtL801, and rtV173L did not significantly affect viral load reduction during adefovir administration. These results demonstrate that the rtL801 mutant is co-selected with rtM2041 as a compensatory mutation in the same manner as rtL180M with rtM204V, and that adefovir shows similar antiviral efficacy against all of the evaluated patterns of lamivudine-resistant HBV mutations. J. Med. Virol. 81:417-424, 2009. (C) 2009 Wiley-Liss, Inc.