Telbivudine与恩替卡韦的不可检测的乙型肝炎病毒DNA：一项随机

StephenW

BMC Gastroenterol. 2017 Jan 19;17(1):15. doi: 10.1186/s12876-017-0572-2.
Telbivudine versus entecavir in patients with undetectable hepatitis B virus DNA: a randomized trial.An J1, Lim YS2, Kim GA3, Han SB4, Jeong W1, Lee D1, Shim JH1, Lee HC1, Lee YS1.
Author information

• 1Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
• 2Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. [email protected].
• 3Health Screening and Promotion Center, Asan Medical Center, Seoul, Republic of Korea.
• 4Department of Applied Statistics, Gachon University, Seongnam-si, Gyeonggi-do, Republic of Korea.
  

AbstractBACKGROUND: Telbivudine has been suggested to induce hepatitis B surface antigen (HBsAg) decline to the similar degree as pegylated interferon. We aimed to investigate whether telbivudine could further decrease HBsAg titer in patients who maintain undetectable serum hepatitis B virus (HBV) DNA after initial entecavir treatment.
METHODS: In this open-label trial, patients who had serum HBsAg and HBV DNA levels ≥1,000 IU/mL and <60 IU/mL, respectively, following entecavir (0.5 mg/day) treatment for HBeAg-positive chronic hepatitis B were randomized to either switch treatment to telbivudine (600 mg/day, n = 47) or continue entecavir (n = 50) for 48 weeks.
RESULTS: The baseline characteristics were comparable between groups including HBsAg levels (median, 3.41 log10 IU/mL). All patients had undetectable HBV DNA and normal alanine aminotransferase level. At week 48, the mean change in serum HBsAg levels was not significantly different between the telbivudine and entecavir groups (-0.03 log10 IU/mL vs. -0.05 log10 IU/mL; P = 0.57). No patient experienced HBsAg seroclearance or HBsAg decline >0.5 log10 IU/mL. Eleven patients (23.4%) in the telbivudine group, but none in the entecavir group, experienced virologic breakthrough (P < 0.001). Seven patients (14.9%) exhibited genotypic resistance mutations (M204I +/- L180M) during the virologic breakthrough.
CONCLUSION: Sequential therapy with entecavir followed by telbivudine resulted in a high rate of virologic breakthrough and drug-resistance without any beneficial effect on HBsAg decline. These results do not support the use of low genetic barrier drugs as a switch treatment strategy in patients who achieve virologic response with high genetic barrier drugs.
TRIAL REGISTRATION: NCT01595685 (date of trial registration: May 8, 2012).


KEYWORDS: HBsAg; Hepatitis B surface antigen; Resistance; Virologic breakthrough; Virologic response

PMID:28103819DOI:10.1186/s12876-017-0572-2

StephenW

BMC Gastroenterol。 2017 Jan 19; 17（1）：15。 doi：10.1186 / s12876-017-0572-2。
Telbivudine与恩替卡韦的不可检测的乙型肝炎病毒DNA：一项随机试验。
An J1，Lim YS2，Kim GA3，Han SB4，Jeong W1，​​Lee D1，Shim JH1，Lee HC1，Lee YS1。
作者信息

    1韩国嵩山医学院大学医学中心肝内科肝脏中心，88岁，奥林匹克43-gil，首尔，宋朝，05505。
    2韩国嵩山医学院As山医学中心肝内科，肝中心，88，奥林匹克43-gil，宋浦区，首尔，05505，韩国。 [email protected]。
    3Health筛选和促进中心，韩国首尔Asan医疗中心。
    4韩国京畿道城南市加川大学应用统计学院。

摘要
背景：

已经建议替比夫定诱导乙型肝炎表面抗原（HBsAg）降低至与聚乙二醇化干扰素类似的程度。我们的目的是调查是否telbivudine可以进一步降低HBsAg效价在初始entecavir治疗后维持检测不到的血清乙型肝炎病毒（HBV）DNA的患者。
方法：

在这项开放标签试验中，HBeAg阳性慢性乙型肝炎的恩替卡韦（0.5mg /天）治疗后分别有血清HBsAg和HBV DNA水平分别≥1000IU / mL和<60 IU / mL的患者随机分配切换治疗至替比夫定（600mg /天，n = 47）或继续恩替卡韦（n = 50）48周。
结果：

基线特征在包括HBsAg水平的组之间（中值，3.41log10IU / mL）是相当的。所有患者均具有不可检测的HBV DNA和正常丙氨酸氨基转移酶水平。在第48周，替比夫定和恩替卡韦组之间血清HBsAg水平的平均变化没有显着差异（-0.03log10IU / mL相对于-0.05log10IU / mL; P = 0.57）。没有患者经历HBsAg血清清除或HBsAg下降> 0.5log10 IU / mL。替比夫定组中的11名患者（23.4％），但恩替卡韦组中没有患者经历病毒学突破（P <0.001）。在病毒学突破中，7名患者（14.9％）表现出基因型抗性突变（M204I +/- L180M）。
结论：

使用恩替卡韦随后替比夫定的顺序疗法导致高的病毒学突破率和耐药性，对HBsAg下降没有任何有益的影响。这些结果不支持使用低遗传屏障药物作为实现具有高遗传屏障药物的病毒学应答的患者的转换治疗策略。
试用注册：

NCT01595685（试验注册日期：2012年5月8日）。
关键词：

HBsAg;乙型肝炎表面抗原;抵抗性;病毒学突破;病毒学反应

PMID：
    28103819
DOI：
    10.1186 / s12876-017-0572-2

月圆

CONCLUSION: Sequential therapy with entecavir followed by telbivudine resulted in a high rate of virologic breakthrough and drug-resistance without any beneficial effect on HBsAg decline. These results do not support the use of low genetic barrier drugs as a switch treatment strategy in patients who achieve virologic response with high genetic barrier drugs.
恩替卡韦抗病毒一段时间后，再改换成替比夫定抗病毒药继续治疗，会导致高几率的病毒飙升，和耐药的发生。而不会有原先期望的HBsAg下降这样的好事发生。
   这个试验结果表明，在使用高耐药屏障的抗病毒药（如恩替卡韦）之后，不要随意换低耐药屏障的药（如替比夫定）继续治疗。
   我认为，此文有些搞笑，恩替抗病毒好好的，谁会去傻傻的换成替比夫定！就是换，也要换成药效更强的替诺吧。
   毕竟替比夫定的药效也不如恩替啊！

StephenW

回复 月圆 的帖子

同意. 有些人认为低病毒载量后, 耐药可能性会很低.