AASLD2018[268]有限的持续反应和缺乏HBsAg 停止长期核后衰退（t

StephenW

268
Limited Sustained Response and Lack of HBsAg
Decline after Stopping Long-Term Nucleos(t)
Ide Analogue Therapy in Hbeag Negative
Patients with Chronic Hepatitis B: Results of a
Prospective, Randomized, Open-Label Phase IV
Trial
Kin Seng Liem1,2, Scott K. Fung3, David KH Wong1, Colina
K. Yim1, Seham Noureldin1, Feng Fei Huang1, Hemant A.
Shah1, Jordan J. Feld1,4, Bettina E. Hansen1,5,6 and Harry L.
A. Janssen1, (1)Toronto Centre for Liver Disease, University
Health Network, (2)Dept. of Gastroenterology & Hepatology,
Erasmus University Medical Center Rotterdam, (3)University
of Toronto, Toronto, on, Canada, (4)Mclaughlin-Rotman
Centre for Global Health, (5)Institute of Health Policy,
Management and Evaluation, University of Toronto, (6)
Department of Gastroenterology & Hepatology, Erasmus
Medical Centre Rotterdam
Background: Chronic hepatitis B (CHB) patients often
receive life-long therapy with nucleos(t)ide analogues (NA). In
this prospective randomized controlled trial we assessed the
proportion of patients with sustained response after stopping
long-term entecavir (ETV) or tenofovir (TDF) therapy.
Methods: Patients at the Toronto Centre for Liver Disease
were included if they had received ETV/TDF therapy for ≥1
year and achieved virologic suppression (defined as HBeAg
seroconversion combined with undetectable HBV DNA ≥ 12
months in HBeAg positive patients, or undetectable HBV DNA
≥ 36 months for start of therapy HBeAg negative patients).
Patients were then randomized 2:1 to stop or continue NA
therapy for 72 weeks. Patients were retreated in case of
persistent HBV DNA>20,000IU/mL, HBeAg seroreversion
or HBV DNA>2,000 with ALT>5xULN (clinical relapse).
Sustained response (HBeAg-negative, HBV DNA <2,000 IU/
mL and normal ALT) at 48 weeks of follow-up was evaluated
in both groups. Results: Of 67 enrolled patients (60% male,
97% Asian), 45 (67%) patients were randomized to stop and
22 (33%) to continue NA therapy. 37/67 (55%) patients lost
HBeAg on NA therapy. At randomization the mean duration of
NA therapy was 8 (4) years and HBsAg level was 3.0 (0.7) log
IU/mL. Sustained response was observed in 11/45 (24%) stop
vs. 22/22 (100%) continue patients at week 48 (see Figure).
Within the stop group 24/45 (53%) patients continued to have
a normal ALT and HBeAg negative status. Fourteen (21%)
patients developed ALT >10x ULN and another 7 (10%) had
ALT >5x ULN. HBsAg loss occurred in two patients (1 per
group). Mean HBsAg decline from randomization to week
48 was 0.1 (0.0-0.3) vs. 0.0 (0.0-0.1) log IU/mL in stop vs.
continue patients (p=0.50) and was not associated with peak
ALT values after stopping (p>0.05). Among patients who
stopped, 13/45 (29%) required retreatment by week 48 (6 had
virologic relapse >20,000IU/mL and 7 had clinical relapse, of
which 1 had HBeAg seroreversion). Median (range) time to
retreatment was 12 (10-30) weeks. No patient experienced
liver decompensation or died. Conclusion: Forty-eight weeks
after stopping NA therapy, only 24% of patients had a sustained
response, while 74% had relapse and 2% had HBsAg loss.
HBsAg levels in the stop group declined marginally and were
not different from the NA continuation group. The findings of
this prospective study in mainly Asian patients demonstrate
no additional benefit of stopping NA therapy. Week 72 results
will be presented at the Meeting.

StephenW

268
有限的持续反应和缺乏HBsAg
停止长期核后衰退（t）
Hbeag阴性的Ide模拟疗法
慢性乙型肝炎患者：a。的结果
前瞻性，随机，开放标签第四阶段
审讯
Kin Seng Liem1,2，Scott K. Fung3，David KH Wong1，Colina
K. Yim1，Seham Noureldin1，Feng Fei Huang1，Hemant A.
Shah1，Jordan J. Feld1,4，Bettina E. Hansen1,5,6和Harry L.
A. Janssen1，（1）多伦多大学肝病中心
卫生网，（2）部门。胃肠病学和肝病学，
鹿特丹伊拉斯姆斯大学医学中心，（3）大学
多伦多，多伦多，加拿大，（4）Mclaughlin-Rotman
全球卫生中心，（5）卫生政策研究所，
多伦多大学管理与评估，（6）
伊拉斯谟的消化内科和肝病学系
鹿特丹医疗中心
背景：慢性乙型肝炎（CHB）患者常有
用核苷（酸）类似物（NA）接受终生治疗。在
这项前瞻性随机对照试验我们对此进行了评估
停药后持续反应的患者比例
长期恩替卡韦（ETV）或替诺福韦（TDF）治疗。
方法：多伦多肝病中心的患者
如果他们接受ETV / TDF治疗≥1，则包括在内
年，并实现了病毒学抑制（定义为HBeAg
血清转换联合不可检测的HBVDNA≥12
HBeAg阳性患者数月，或HBV DNA检测不到
开始治疗HBeAg阴性患者≥36个月）。
然后患者以2：1随机化以停止或继续NA
治疗72周。患者在以下情况下撤退
持续性HBV DNA> 20,000IU / mL，HBeAg血清反转
或HBV DNA> 2,000，ALT> 5xULN（临床复发）。
持续反应（HBeAg阴性，HBV DNA <2,000 IU /
评估随访48周时的mL和正常ALT）
在两组中。结果：67名入选患者（60％为男性，
97％的亚洲人），45名（67％）患者随机停止治疗
22（33％）继续NA治疗。 37/67（55％）患者失去了
NA治疗的HBeAg。在随机化的平均持续时间
NA治疗为8（4）年，HBsAg水平为3.0（0.7）log
IU /毫升。在11/45（24％）停止时观察到持续反应
与第22/22（100％）相比，第48周继续患者（见图）。
在停止组24/45（53％）患者继续有
正常的ALT和HBeAg阴性状态。十四（21％）
患者发生ALT> 10x ULN，另有7（10％）患者
ALT> 5x ULN。两名患者发生HBsAg丢失（1名患者）
组）。平均HBsAg从随机化到周减少
停止时48对0.1（0.0-0.3）对0.0（0.0-0.1）log IU / mL
继续患者（p = 0.50）并且与峰值无关
停止后的ALT值（p> 0.05）。在患者中
停止了，13/45（29％）要求在第48周进行再治疗（6人有
病毒学复发> 20,000IU / mL，7例临床复发
哪1人有HBeAg血清转换）。中位数（范围）时间
再治疗12（10-30）周。没有患者经历过
肝脏失代偿或死亡。结论：四十八周
停止NA治疗后，只有24％的患者有持续性
反应，74％复发，2％HBsAg丢失。
停止组中的HBsAg水平略有下降且为
与NA继续组没有什么不同。调查结果
这项前瞻性研究主要针对亚洲患者
停止NA治疗没有额外的好处。第72周结果
将在会上提交。