替比夫定加阿德福韦治疗慢性乙型肝炎患者的病毒学突破或

StephenW

Eur J Gastroenterol Hepatol. 2013 Feb 11. [Epub ahead of print]
Telbivudine plus adefovir therapy for chronic hepatitis B patients with virological breakthrough or genotypic resistance to telbivudine.
Zhang Y, Lian JQ, Li Y, Wang JP, Huang CX, Bai XF, Wang JP.
Source
aCenter for Infectious Diseases bDepartment of Pharmacology, Tangdu Hospital, Fourth Military Medical University cDepartment of Infectious Diseases, Shaanxi Provincial People's Hospital, Xi'an, China.

Abstract
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.

StephenW

替比夫定（LDT）的管理经验是非常有限的，相关的病毒学突破（VBT），阻力在治疗慢性乙型肝炎（CHB）患者，并指引建议的原始基础上的抢救治疗的一般原则核苷（t）的，IDE模拟电阻。本研究的目的是确定的影响，增加了阿德福韦酯（ADV），乙肝e抗原（HBeAg）阳性的慢性乙型肝炎患者VBT或抗LDT。
方法：

VBT和31例确诊基因型耐药LDT 36个CHB患者进行了登记，并于其后处理相结合的LDT和ADV为12个月。
结果：

联合治疗是安全的，多数患者耐受性的治疗。 LDT + ADV导致的病毒载量迅速下降，并持续抑制病毒复制，与2.17（VBT）和2.31（电阻）log10拷贝/ ml抢救治疗后12个月减少的分别。相应的病毒学和生化反应率分别为两个组之间的相似结束时的观测值（病毒学应答70.3％和74.2％，P = 0.720; 64.0％和65.5％的生化反应，P = 0.907）。与VBT患者的血清学反应的累积较高比那些性（35.1％和9.67％，HBeAg转阴，P = 0.014; 10.8％和3.23％，血清HBeAg /抗-HBe血清转换，P = 0.233）。
结论：

LDT和ADV联合治疗显着降低血清乙肝病毒DNA水平和谷丙转氨酶水平正常化的患者VBT或基因型耐药LDT。救援策略也确认LDT-VBT患者的HBeAg血清学结果的发生率较高。