Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
Gut. 2016 May;65(5):852-60. doi: 10.1136/gutjnl-2014-308353. Epub 2015 Jan 16.
Little clinical data are available regarding the optimal treatment of patients who harbour entecavir (ETV)-resistant HBV.
In this multicentre randomised trial, patients who had HBV with ETV resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL were randomised to receive tenofovir disoproxil fumarate (TDF, 300 mg/day) monotherapy (n=45) or TDF and ETV (1 mg/day) combination therapy (n=45) for 48 weeks.
Baseline characteristics were comparable between groups, including HBV DNA levels (median, 4.02 log10 IU/mL) and hepatitis B e antigen-positivity (89%). All patients had at least one ETV-resistance mutation: rtT184A/C/F/G/I/L/S (n=49), rtS202G (n=43) and rtM250L/V (n=7), in addition to rtM204V/I (n=90). All except one patient in the TDF group completed 48 weeks of treatment. At week 48, the proportion of patients with HBV DNA <15 IU/mL, the primary efficacy endpoint, was not significantly different between the TDF and TDF+ETV groups (71% vs. 73%; p>0.99). The mean change in HBV DNA levels from baseline was not significantly different between groups (-3.66 vs. -3.74 log10 IU/mL; p=0.81). Virological breakthrough occurred in one patient on TDF, which was attributed to poor drug adherence. At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, retained their baseline resistance mutations (p>0.99). None developed additional resistance mutations. Safety profiles were comparable in the two groups.
TDF monotherapy for 48 weeks provided a virological response comparable to that of TDF and ETV combination therapy in patients infected with ETV-resistant HBV.
ClinicalTrials.gov ID NCT01639092.
关于恩替卡韦（ETV）耐药乙型肝炎病毒（HBV）患者的最佳治疗方法，临床数据有限。
在这项多中心随机试验中，对 HBV 伴 ETV 耐药相关突变且血清 HBV DNA 浓度>60IU/mL 的患者进行随机分组，分别接受富马酸替诺福韦二吡呋酯（TDF，300mg/天）单药治疗（n=45）或 TDF 和 ETV（1mg/天）联合治疗（n=45）48 周。
两组患者的基线特征相当，包括 HBV DNA 水平（中位数，4.02log10IU/mL）和乙型肝炎 e 抗原阳性率（89%）。所有患者均至少存在一种 ETV 耐药突变：rtT184A/C/F/G/I/L/S（n=49）、rtS202G（n=43）和 rtM250L/V（n=7），此外还有 rtM204V/I（n=90）。TDF 组除 1 例患者外，其余患者均完成了 48 周的治疗。第 48 周时，主要疗效终点 HBV DNA<15IU/mL 的患者比例在 TDF 组和 TDF+ETV 组之间无显著差异（71%比 73%；p>0.99）。两组患者的 HBV DNA 水平自基线的平均变化无显著差异（-3.66比-3.74log10IU/mL；p=0.81）。TDF 组有 1 例患者发生病毒学突破，归因于药物依从性差。第 48 周时，TDF 组和 TDF+ETV 组分别有 6 例和 3 例患者保留了基线耐药突变（p>0.99）。均未出现新的耐药突变。两组的安全性特征相当。
对于感染 ETV 耐药 HBV 的患者，TDF 单药治疗 48 周可获得与 TDF+ETV 联合治疗相当的病毒学应答。
ClinicalTrials.gov 编号 NCT01639092。
