Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepatitis B viruses in patients
Activity of adefovir dipivoxil against all patterns of lamivudine-resistant hepatitis B viruses in patients
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DOI：
10.1111/j.1365-2893.2005.00578.x
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发表时间：
2005-01-01
影响因子：
2.5
通讯作者：
Xiong, S
中科院分区：
文献类型：
--
作者：
Westland, CE;Yang, H;Xiong, S
131例肝移植后慢性B型肝炎和拉米夫定治疗失败的患者，通过杂交检测可检测到血清B型肝炎病毒（HBV）脱氧核糖核酸，或通过聚合酶链反应大于或等于1 × 10（6）拷贝/mL，尽管连续使用拉米夫定，丙氨酸转氨酶水平仍升高，入选阿德福韦酯开放标签研究。对基线样本的HBV聚合酶的B和C结构域进行测序，以确定是否存在拉米夫定耐药突变。结果显示，98%的样本存在酪氨酸-甲硫氨酸-谷氨酸-天冬氨酸（YMDD）突变，表明上述拉米夫定治疗失败的临床定义与YMDD突变的存在之间存在强相关性。除了rtM 204 V/I和rtL 180 M突变外，还在19%的患者中发现了rtV 173 L突变。拉米夫定耐药HBV主要有4种模式：rtL 180 M + rtM 204 V（60%）、rtV 173 L + rtL 180 M + rtM 204 V（19%）、rtM 204 I（9%）和rtL 180 M + rtM 204 I（9%）。阿德福韦酯治疗拉米夫定耐药病毒患者的抗病毒疗效相似，从所有四个模式。
One hundred and thirty-one post-liver transplantation patients with chronic hepatitis B and failing lamivudine therapy with detectable serum hepatitis B virus (HBV) deoxyribonucleic acid by hybridization assays or greater than or equal to1 x 10(6) copies/mL by polymerase chain reaction, and elevated alanine transaminase levels despite continuous lamivudine, were enrolled in an open-label study of adefovir dipivoxil. The B and C domains of HBV polymerase were sequenced for baseline samples to determine the presence of lamivudine resistance mutations. The results showed that 98% of the samples had tyrosine-methionine-aspartate-aspartate (YMDD) mutations, indicating a strong correlation between the above clinical definition of lamivudine treatment failure and the presence of YMDD mutations. In addition to the rtM204V/I and the rtL180M mutations, the mutation rtV173L was identified in 19% of patients. Four major patterns of lamivudine-resistant HBV were identified: rtL180M + rtM204V (60%), rtV173L + rtL180M + rtM204V (19%), rtM204I (9%) and rtL180M + rtM204I (9%). Treatment with adefovir dipivoxil showed similar antiviral efficacy in patients with lamivudine-resistant virus from all four patterns.