替比联合阿德治疗替比病毒突破或基因型耐药乙型肝炎患者

StephenW

European Journal of Gastroenterology & Hepatology:
July 2013 - Volume 25 - Issue 7 - p 814-819
doi: 10.1097/MEG.0b013e32835ee516
Original Articles: Hepatitis
替比夫定联合阿德福韦治疗慢性乙型肝炎患者
病毒学突破或基因型耐药，替比夫定
Telbivudine plus adefovir therapy for chronic hepatitis B patients with
virological breakthrough or genotypic resistance to telbivudine

Zhang, Yea,*; Lian, Jian-Qia,*; Li, Yuc,*; Wang, Jie-Pinb,*; Huang,
Chang-Xinga; Bai, Xue-Fana; Wang, Jiu-Pinga


Background/aim: There is very limited experience in the management of
telbivudine (LdT)-associated virological breakthrough (VBT) and resistance
in the treatment of chronic hepatitis B (CHB) patients, and the guideline
recommendations are primitively based on the general principles of rescue
therapy to nucleos(t)ide analog resistance. The aim of this study is to
determine the effect of the addition of adefovir (ADV) in hepatitis B e
antigen (HBeAg)-positive CHB patients with VBT or resistance to LdT.
Methods: Thirty-seven CHB patients with confirmed VBT and 31 patients with
genotypic resistance to LdT were enrolled and thereafter treated with a
combination of LdT and ADV for 12 months.
Results: Combination therapy was
safe and the majority of patients tolerated the therapy. LdT+ADV led to
rapid decreases in viral loads, and viral replications were persistently
suppressed, with 2.17 (VBT) and 2.31 (resistance) log10 copies/ml
reductions 12 months after rescue therapy, respectively. The rates
corresponding to virological and biochemical responses were similar between
the two groups at the end of observations (70.3 vs. 74.2% for virological
response, P=0.720; 64.0 vs. 65.5% for biochemical response, P=0.907). The
cumulative rates of serological responses were higher in patients with VBT
than in those with resistance (35.1 vs. 9.67% for HBeAg loss, P=0.014; 10.8
vs. 3.23% for HBeAg/anti-HBe seroconversion, P=0.233).
Conclusion: LdT and
ADV combination therapy led to significant decreases in serum hepatitis B
virus DNA levels and normalization of alanine aminotransferase levels in
patients with VBT or genotypic resistance to LdT. This rescue strategy was
also associated with a higher rate of HBeAg serological outcomes in
patients with confirmed LdT-related VBT.

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StephenW

背景/目的：有管理的经验非常有限
替比夫定（LDT）相关的病毒学突破（VBT）和
耐药慢性乙型肝炎（CHB）患者，在治疗的方针
建议原始的基础上救援的一般原则
治疗核苷（酸）IDE模拟耐药。这项研究的目的是
乙肝e阿德福韦（ADV）此外，在确定的效果
抗原（HBeAg）阳性的慢性乙型肝炎患者VBT或抗LDT。
方法37例慢性乙型肝炎患者确认VBT和31例
基因型耐药LDT入选，其后与治疗
相结合的LDT和ADV 12个月。
结果：联合治疗
安全和广大患者耐受治疗。 LDT + ADV导致
持续的病毒载量的快速下降，病毒复制
打压，2.17（VBT）和2.31（耐药）log10拷贝/毫升
抢救治疗后12个月减少。率
相应的病毒学和生化反应之间的相似
观测结束时两组（70.3对比74.2％病毒学
响应，P = 0.720;生化反应的64.0％和65.5％，P = 0.907）。该
累计血清学反应率较高，患者VBT
比耐药（HBeAg转阴35.1％和9.67％，P = 0.014; 10.8
与3.23％的HBeAg /抗HBe血清转换，P = 0.233）。 LDT和
结论：
ADV联合治疗显着降低血清中乙肝
病毒DNA水平和谷丙转氨酶水平正常化
VBT或基因型耐药LDT的患者。这种救援策略
率较高的HBeAg血清学结果也与
患者证实LDT-VBT。