AASLD2016[1841 ♦]切换到替诺福韦 对 持续性恩替卡韦

StephenW

1841 ♦
Switching to Tenofovir versus Continuing Entecavir
in Chronic Hepatitis B Patients with Partial Virologic
Response during Entecavir Therapy: STEEP Study
Hyung Joon Yim1, In Hee Kim2, Sang Jun Suh1, Young Kul Jung1,8,
Ji Hoon Kim6, Yeon Seok Seo7, Jong Eun Yeon6, Chang Wook
Kim3, So Young Kwon4, Sang Hoon Park5, Myung Seok Lee5,
Soon Ho Um7, Kwan Soo Byun6; 1Internal Medicine, Korea University
Ansan Hospital, Ansan, Korea (the Republic of); 2Internal Medicine,
Chonbuk National University Hospital, JeonJu, Korea (the
Republic of); 3Internal Medicine, The Catholic University of Korea
Uijeongbu St. Mary’s Hospital, Uijeongbu, Korea (the Republic
of); 4Internal Medicine, Konkuk University Hospital, Seoul, Korea
(the Republic of); 5Internal Medicine, Hallym University Kangnam
Sacred Heart Hospital, Seoul, Korea (the Republic of); 6Internal
Medicine, Korea University Guro Hospital, Seoul, Korea (the
Republic of); 7Internal Medicine, Korea University Anam Hospital,
Seoul, Korea (the Republic of); 8Internal Medicine, Gachon University
Gil Hospital, Incheon, Korea (the Republic of)
Background Entecavir has been widely used for treatment-naïve
chronic hepatitis B (CHB) patients. However, about 20% of
patients show partial virologic response (PVR) after 2 year of
entecavir therapy [Yoon, et al, 2011]. If the HBV DNA continues
to be detected, underlying liver disease may progress, and
the risk of hepatocellular carcinoma can be increased. Therefore,
switching to a more effective and potent antiviral therapy
may be needed. In this study, we compared the efficacy of
switching to tenofovir with continuing entecavir in CHB patients
who showed PVR to entecavir. Patients and Methods This is an
investigator initiated open label randomized controlled trial
conducted in Korea between April 2013 and December 2015.
Primary end point was a virologic response (HBV DNA < 20
IU/mL) rate at year 1 (12 months). Secondary end points were
degree of HBV DNA reduction, mean levels of HBV DNA, biochemical
and serologic response rates, virologic breakthrough,
antiviral resistance, and adverse events. We included CHB
patients receiving entecavir 0.5 mg more than 12 months,
but having datable HBV DNA over 60 IU/mL despite no resistance
to entecavir. Results A total of 45 patients were enrolled.
Twenty two patients were randomized to tenofovir arm and
23 patients to entecavir arm. Baseline characteristics were not
significantly different between the groups. After 12 months
of treatment, virologic response rate was significantly higher
in the tenofovir group compared with in the entecavir group
by per protocol analysis (55% vs 20%, P = 0.022) as well as
intention-to-treat analysis (50% vs 17.4%, P = 0.020). At month
12, the mean HBV DNA level was lower (1.54 vs. 2.01 log
IU/mL, P = 0.011) and the degree of HBV DNA reduction was
greater (-1.13 vs. -0.67 log IU/mL, P = 0.024) in the tenofovir
group than in the entecavir group, respectively. Proportions of
patients with normal ALT and HBeAg loss/seroconversion rates
were not different between the groups. There was no virologic
breakthrough in both groups, and no significant adverse events
were observed. We also analyzed factors related to virologic
response by multivariate logistic regression model. Baseline
serum HBV DNA level (Odds ratio 0.152 [0.030-0.786], P =
0.025) and type of antiviral agent (Odds ratio 6.661 [1.421-
31.233], P = 0.016) were significant factors. Conclusion In
CHB patients with PVR to entecavir, switching to tenofovir
resulted in higher virologic response rate and better suppression
of viral replication than continuing entecavir. Therefore,
switching to tenofovir would be a better strategy in entecavir
partial responders to achieve optimal response.
Disclosures:
Chang Wook Kim - Consulting: Gilead Korea; Grant/Research Support: BMS
Korea, Gilead Korea, Daewoong, Pharmicell; Speaking and Teaching: BMS
Korea, Daewoong
Kwan Soo Byun - Grant/Research Support: Gilead, BMS
The following people have nothing to disclose: Hyung Joon Yim, In Hee Kim,
Sang Jun Suh, Young Kul Jung, Ji Hoon Kim, Yeon Seok Seo, Jong Eun Yeon, So
Young Kwon, Sang Hoon Park, Myung Seok Lee, Soon Ho Um

StephenW

AASLD2016 [1841♦]切换到替诺福韦对持续性恩替卡韦
切换到替诺福韦对持续性恩替卡韦
在慢性乙型肝炎患者部分病毒学
恩替卡韦治疗期间的反应：STEEP研究
Hyung Joon Yim1，He He Kim2，Sang Jun Suh1，Young Kul Jung1,8，
Ji Hoon Kim6，Yeon Seok Seo7，Jong Eun Yeon6，Chang Wook
Kim3，So Young Kwon4，Sang Hoon Park5，Myung Seok Lee5，
很快Ho Um7，Kwan Soo Byun6; 1韩国大学内科学
韩国安山医院（共和国）; 2内科，
韩国全州国立大学医院
共和国）; 3韩国天主教大学内科
韩国Uijeongbu圣玛丽医院（共和国
的）; 4内科，Konkuk大学医院，韩国首尔
（共和国）; 5内蒙古大学医学院
圣心医院，韩国首尔（共和国）; 6内部
医学，韩国大学古罗医院，韩国首尔（
共和国）; 7内科，韩国大学Anam医院，
韩国首尔（共和国）; 8加on大学内科
韩国仁川医院（共和国）
背景恩替卡韦已广泛用于治疗天真
慢性乙型肝炎（CHB）患者。然而，约20％
患者在2年后显示部分病毒学应答（PVR）
恩替卡韦治疗[Yoon，等人，2011]。如果HBV DNA继续
待检测，潜在的肝脏疾病可以进展，和
可以增加肝细胞癌的风险。因此，
切换到更有效和有效的抗病毒治疗
可能需要。在这项研究中，我们比较了疗效
在CHB患者中切换到替诺福韦与连续恩替卡韦
他们对恩替卡韦显示PVR。病人和方法这是一个
研究者发起了开放标签随机对照试验
在2013年4月至2015年12月期间在韩国举行。
主要终点是病毒学应答（HBV DNA <20
IU / mL）比率在第1年（12个月）。次要终点
HBV DNA降低程度，HBV DNA平均水平，生化指标
和血清学反应率，病毒学突破，
抗病毒抗性和不良事件。我们包括CHB
患者接受恩替卡韦0.5 mg超过12个月，
但具有超过60IU / mL的可用HBV DNA，尽管没有抗性
到恩替卡韦。结果共招募45名患者。
二十二名患者被随机分配到替诺福韦组
23例恩替卡韦组。基线特征不是
显着不同。 12个月后
的治疗，病毒学应答率明显较高
在替诺福韦组中与恩替卡韦组相比
通过方案分析（55％对20％，P = 0.022）以及
意向性治疗分析（50％对17.4％，P = 0.020）。月份
12，平均HBV DNA水平较低（1.54对2.01对数
IU / mL，P = 0.011），HBV DNA减少程度为
在替诺福韦中更大（-1.13对-0.67log IU / mL，P = 0.024）
组比恩替卡韦组分别。比例
具有正常ALT和HBeAg丧失/血清转化率的患者
在组之间没有差异。没有病毒学
两组均有突破，无明显不良事件
。我们还分析了与病毒相关的因素
多因素logistic回归模型。基线
血清HBV DNA水平（比值比0.152 [0.030-0.786]，P =
0.025）和抗病毒药的类型（赔率比6.661 [1.421-
31.233]，P = 0.016）。结论在
CHB患者PVR对恩替卡韦，切换到替诺福韦
导致更高的病毒学反应率和更好的抑制
的病毒复制比继续恩替卡韦。因此，
切换到替诺福韦将是一个更好的策略在恩替卡韦
部分响应者实现最佳反应。
披露：
张惠金 - 咨询：吉利德韩国;资助/研究支持：BMS
韩国，吉利德韩国，大宇，Pharmicell;口语和教学：BMS
韩国，大宇
Kwan Soo Byun - 资助/研究支持：Gilead，BMS
以下人士没有透露：Hyung Joon Yim，In Hee Kim，
Sang Jun Suh，Young Kul Jung，Ji Hoon Kim，Yeon Seok Seo，Jong Eun Yeon，So
Young Kwon，Sang Hoon Park，Myung Seok Lee，Soon Ho Um