Characteristics of adefovir resistance in patients with or without lamivudine-re

StephenW

<http://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02416.x/abstract>

Characteristics of adefovir resistance in patients with or without
lamivudine-resistant hepatitis B virus treated with adefovir: a 4-year
experience

Chien-Hung Chen, Jing-Houng Wang, Sheng-Nan Lu, Tsung-Hui Hu, Chao-Hung Hung,
Min-Hui Chang, Chi-Sin Changchien, Chuan-Mo LeeArticle first

published online: 8 DEC 2010
DOI: 10.1111/j.1478-3231.2010.02416.x
© 2010 John Wiley & Sons A/S
Issue

Liver International
Volume 31, Issue 2, pages 206–214, February 2011

Abstract

Background/Aim: We investigated the 4-year incidence and predictors of adefovir
resistance in chronic hepatitis B patients with or without lamivudine
(LAM)-resistance treated with adefovir dipivoxil with or without short-term LAM
overlapping.

Methods: One hundred and two LAM-resistant patients and 79 without LAM
resistance (36 naïve and 43 prior LAM exposure) treated with adefovir for >12
months were prospectively examined.

Results: Cumulative incidences of adefovir resistance at month 12, 24, 36 and 48
were 3.9, 21.1, 31.8 and 43% respectively in LAM-resistant patients. Cirrhosis
was a significant risk factor for adefovir resistance. A similar rate of
adefovir resistance was observed for LAM-resistant patients and those with prior
LAM exposure without resistance. Regarding LAM-resistant patients, compared with
those having hepatitis B virus (HBV) DNA levels <300 copies/ml, patients having
HBV DNA levels >104 copies/ml at week 24 of therapy had a hazard ratio (HR) of
9.8 for adefovir resistance development, while those without LAM resistance
having the same HBV DNA levels at week 48 had a similar HR (9.5).
Multidrug-resistant (LAM+adefovir) variants were detected by direct sequencing
in three of 35 LAM-resistant patients treated with a switch to adefovir. Two of
them had resistant mutations to both drugs on the same viral genome as
determined by molecular cloning and sequencing.

Conclusion: The incidence of adefovir resistance was high in LAM-resistant
patients treated with sequential adefovir. High HBV DNA levels at week 24 and 48
of therapy were the strongest predictors for adefovir resistance development in
patients with and without LAM resistance respectively.

患者的特点，有或没有阿德福韦耐药
拉米夫定抗乙型肝炎病毒阿德福韦治疗：4年
经验

陈建宏，王景弘，卢胜男，崇辉胡朝鸿鸿，
闽辉张简吉幸，传武LeeArticle第一

发表时间：2010年12月8日
分类号：10.1111/j.1478-3231.2010.02416.x
© 2010约翰Wiley＆Sons出版A / S公司
发行

国际肝病
第31卷，第2期，页206-214，2011年2月

摘要

背景/目的：我们研究了4年的发病率和阿德福韦预测
慢性乙型肝炎患者拉米夫定耐药或不
（林）电阻与阿德福韦治疗或无短期林
重叠。

方法：一百二林耐患者和79所没有林
电阻（36天真和43林前曝光），阿德福韦为> 12名接受治疗
个月的前瞻性研究。

结果：阿德福韦耐药的发生率在12个月累计，24，36和48
分别为3.9，21.1，31.8和43％分别在林耐患者。硬化
阿德福韦耐药是一个重要的危险因素。类似率
阿德福韦耐药性观察林耐病人和那些事先
林曝光无阻力。关于林，耐药患者，而
那些有乙型肝炎病毒（HBV）的DNA水平“300拷贝/毫升，病人有
乙肝病毒DNA含量> 24周时104拷贝/ ml的治疗有危险比（HR）为
阿德福韦耐药性的发展为9.8，而没有这些，林耐
48周时有相同的HBV DNA水平也有类似的人力资源（9.5）。
多药耐药（林+阿德福韦）变种直接测序法检测
在35个林耐带开关三阿德福韦治疗的患者。两种
他们对病毒基因组相同，以这两种药物耐药基因突变
由分子克隆和序列分析。

结论：阿德福韦耐药的发生率高林耐
序贯阿德福韦治疗的患者。 HBV DNA水平高24和48周
分别为阿德福韦治疗抗性发展中的最强预测因子
患者和无林分别阻力。