[英语,临床,推荐]Clinical course of lam+adefovir therapy for lam-resistant

StephenW

J Med Virol. 2011 Jun;83(6):953-61. doi: 10.1002/jmv.22025.

Clinical course and predictive factors of virological response in long-term
lamivudine plus adefovir dipivoxil combination therapy for
lamivudine-resistant chronic hepatitis B patients.

Aizawa M, Tsubota A, Fujise K, Tatsuzawa K, Kono M, Hoshina S, Tajiri H.

Source
Department of Gastroenterology and Hepatology, Kashiwa Hospital, Jikei
University School of Medicine, Chiba, Japan; Department of Gastroenterology
and Hepatology, Jikei University Hospital, Jikei University School of
Medicine, Tokyo, Japan. [email protected].

Abstract
The aims of this study were to assess the long-term efficacy of lamivudine
(LAM) plus adefovir dipivoxil (ADV) combination therapy in patients with
chronic hepatitis B resistant to LAM, to identify predictive factors of
complete viral response (HBV-DNA <2.6 log copies/ml at 12 months of
combination therapy), and to analyze amino acid substitutions associated
with treatment resistance in the hepatitis B virus (HBV) genome.
Seventy-two patients who received ADV in addition to LAM for breakthrough
hepatitis were enrolled. Undetectable HBV-DNA was observed in 61%, 74%,
81%, 84%, and 85% at 12, 24, 36, 48, and 60 months of combination therapy,
respectively. On multivariate analysis, undetectable HBV-DNA during the
preceding LAM monotherapy (P < 0.0001), alanine aminotransferase
value ≥ the upper limit of normal × 6 (P = 0.006) and
HBV-DNA level < 6.0 log copies/ml at the initiation of combination
therapy (P = 0.007) were independent significant predictors of complete
viral response. The cumulative rate of undetectable HBV-DNA was
significantly higher in patients with response to the preceding LAM
monotherapy than in those with poor response to it. Breakthrough hepatitis
occurred in three patients without complete viral response and with poor
response to the preceding LAM monotherapy, and rtA181A/V substitution was
detected in one of the three patients. In conclusion, undetectable HBV-DNA
during the LAM monotherapy was the strongest independent predictor of
complete viral response to the following combination therapy. The efficacy
of LAM plus ADV combination therapy may be determined by viral response to
the preceding LAM monotherapy.

J. Med. Virol. 83:953-961, 2011. © 2011 Wiley-Liss, Inc.
Copyright © 2011 Wiley-Liss, Inc.

StephenW

医志病毒学杂志。 2011年六月，83（6）:953 - 61。分类号：10.1002/jmv.22025。

临床病程和病毒学应答的预测因素长期
加拉米夫定联合阿德福韦酯治疗
拉米夫定耐药的慢性乙型肝炎患者。

相泽男，Tsubota甲，Fujise钾，Tatsuzawa钾，河野男，保科秒，田尻阁下

来源
胃肠病学和肝病学系，柏医院，慈惠
大学医学院，日本千叶，消化内科
和肝病，慈惠大学医院，慈惠大学法学院
医药，东京，日本。 [email protected]。

摘要
其目的是评估拉米夫定长期疗效研究
（林）加上阿德福韦酯（2009/07）联合治疗的患者
慢性乙型肝炎抗林，以确定预测因子
完整的病毒反应（HBV - DNA的<2.6 log拷贝/毫升在12个月
联合治疗），并分析相关的氨基酸替换
与治疗乙型肝炎病毒（HBV）基因组阻力。
七十个病人谁收到除腺病毒为突破林
肝炎患者。测不到HBV - DNA的观察了61％，74％，
81％，84％和85，12，24，36％，48和60个月的治疗相结合，
分别。多变量分析，测不到HBV - DNA的过程中
林前单用性（P“0.0001），谷丙转氨酶
值≥正常× 6上限性（P = 0.006），
乙肝病毒DNA水平<组合开始在6.0 log拷贝/毫升
治疗（P = 0.007）是完全的独立预测因子
病毒反应。对无法检测HBV - DNA的累积率
患者显着高于前林回应
单药治疗的反应比它差​​的。突破肝炎
三例发生在没有完整的病毒反应，并与贫困
针对上述单一林和rtA181A /视频替代了
发现在三个病人。总之，不到HBV - DNA的
在林单药治疗是最强的独立预测因子
完整的病毒响应以下综合疗法。疗效
林加上阿德福韦的联合治疗可能是由病毒反应
前面的林单药治疗。

j的医科大学。病毒学杂志。 83:953-961，2011。 © 2011威利-利斯公司
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