AASLD2020[24]真实世界的单中心体验 终止长期核苷类似物的功效

StephenW

24
REAL WORLD SINGLE CENTER EXPERIENCE ON THE
EFFICACY OF STOPPING LONG TERM NUCLEOS(T)IDE ANALOG
THERAPY IN PATIENTS WITH CHRONIC HEPATITIS B
Hassan Azhari1, Alexandra Frolkis2, Abdel-Aziz Shaheen1,
Heidi Israelson1, Jacqueline Pinto1, Stephen E. Congly1,
Meredith A. Borman1, Alex Aspinall1, Laura M. Stinton1,
Mark Gordon Swain1, Kelly W Burak1, Samuel S Lee1,
Matthew Sadler1 and Carla S. Coffin1, (1)Gastroenterology &
Hepatology, University of Calgary, (2)Medicine, University of
Calgary
Background: Nucleos(t)ide analogs (NA) suppress hepatitis
B virus (HBV) replication but have minimal effect on the
intrahepatic HBV cccDNA template and rarely lead to HBsAg
loss, requiring prolonged therapy Although expert guidelines
recommend that HBeAg (+) patients may stop NA after
achieving HBeAg seroconversion and consolidation therapy,
many relapse with treatment cessation In HBeAg (-) chronic
hepatitis B (CHB) some studies report that NAs can be
safely stopped in non-cirrhotic patients with undetectable
HBV DNA and quantitative (q)HBsAg levels <100 IU/mL
This study aimed to determine baseline clinical factors that
are associated with off-treatment NA durability Methods: In
this observational cohort study conducted at the Liver Unit
of the University of Calgary in Calgary, AB, Canada, we
reviewed all NA treated patients who stopped long-term NA
therapy based on physician recommendation at our centre
Baseline characteristics including age, sex, ethnicity, HBV
infection profile, and liver stiffness by transient elastrography
(FibroScan®) were collected Data after stopping therapy
was collected as per standard of care (i e , qHBsAg, ALT,
HBV DNA) Categorical variables were compared using
Chi-squared and Fisher’s exact tests Continuous variables
were compared using Wilcoxon rank-sum tests Results:
Among 1,337 CHB patients on long-term NA, 47 stopped
therapy (29 8% Female, 78% East Asian, median age 56
years, range 18-74 years), 28/47 were on tenofovir disoproxil
fumarate, 16 on entecavir, and 3 on lamivudine (including 2
with adefovir combination) All were HBeAg (-) at the time of
NA discontinuation and 46/47 had undetectable HBV DNA
Median liver stiffness was 5 2 kPa (range 3 3-6 6kPa) Six
patients (qHBsAg at NA discontinuation 205, 147, 74, 21, 5 4,
2.3) restarted NA due to a virologic flare defined as HBV DNA
>2000IU/mL (median HBV DNA 4,663 IU/mL, range 265 –
152,043,102 IU/mL) and/or biochemical flare defined as ALT
>2xULN (ALT 208, 938, 1467, 139, 828, 149 respectively).
None developed hepatic dysfunction, and all responded to
restarting NA with suppressed HBV DNA Factors associated
with needing to restart NA included baseline HBeAg (+) status
pre-treatment (n=3; 50% in the relapse group; n=5; 12% in
the non-relapse group; p=0 004) and longer NA treatment
duration (median duration 12 4 years in the relapse group;
6 1 years in the non-relapse group, p=0 011) Age, sex, liver
stiffness, NA, ethnicity, and qHBsAg level at stopping were not
associated with relapse risk Our data suggests that patients
HEPATOLOGY, VOLUME 72, NUMBER 1 (SUPPL) AASLD ABSTRACTS (Oral) 21A
a Denotes AASLD Foundation Abstract Award Recipient
who experience a flare up do so within the first 6 months of
discontinuing NAs, and are less likely to have a flare up once
this period has passed safely Conclusion: Stopping longterm
NA is feasible in HBeAg negative CHB with qHBsAg
<100IU/mL, however severe ALT flares can occur warranting
close follow-up The majority of biochemical and virological
flares occur within the first 6 months of treatment cessation.

StephenW

24
真实世界的单中心体验
终止长期核苷类似物的功效
慢性乙型肝炎患者的治疗
哈桑·阿扎里1，亚历山德拉·弗罗基斯2，阿卜杜勒·阿齐兹·沙欣1，
Heidi Israelson1，Jacqueline Pinto1，Stephen E.Congly1，
Meredith A.Borman1，Alex Aspinall1，Laura M.Stinton1，
Mark Gordon Swain1，Kelly W Burak1，Samuel S Lee1，
Matthew Sadler1和Carla S.Coffin1，（1）胃肠病学与
卡尔加里大学肝病学，（2）
卡尔加里
背景：核苷（核苷酸）类似物（NA）可抑制肝炎
B病毒（HBV）复制，但对
肝内HBV cccDNA模板，很少导致HBsAg
丢失，需要长时间治疗尽管专家指南
建议HBeAg（+）患者可以在术后停止NA
实现HBeAg血清转化和巩固治疗，
HBeAg（-）慢性感染可导致许多停药复发
乙型肝炎（CHB）一些研究报告说，NAs可能是
在无法检测到的非肝硬化患者中安全停止
HBV DNA和定量（q）HBsAg水平<100 IU / mL
这项研究旨在确定基线临床因素，
与未经处理的NA耐久性相关联：
在肝脏科进行的这项观察性队列研究
加拿大卡尔加里卡尔加里大学的
回顾了所有停止长期NA的NA治疗患者
根据我们中心医师的推荐进行治疗
基线特征，包括年龄，性别，种族，乙肝病毒
瞬时弹力描记法检查感染情况和肝脏僵硬
（FibroScan®）停止治疗后收集数据
根据护理标准（即qHBsAg，ALT，
HBV DNA）分类变量使用
卡方检验和Fisher精确检验连续变量
使用Wilcoxon秩和检验对结果进行了比较：
在1,337例长期不适用的CHB患者中，有47例停止
治疗（29 8％女性，78％东亚，中位年龄56岁
年，范围18-74岁），28/47接受替诺福韦酯
富马酸，恩替卡韦16，拉米夫定3（包括2
与阿德福韦合用）时，均为HBeAg（-）
NA停药和46/47的HBV DNA检测不到
肝硬度中位数为5 2 kPa（范围3 3-6 6kPa）6
患者（NA停用时的qHBsAg 205、147、74、21、5、4，
2.3）由于病毒爆发被定义为HBV DNA而重新启动了NA
> 2000IU / mL（中位HBV DNA 4,663 IU / mL，范围265 –
152,043,102 IU / mL）和/或生化耀斑定义为ALT
> 2xULN（分别为ALT 208、938、1467、139、828、149）。
没有人发展为肝功能障碍，并且所有人都对
用抑制的HBV DNA因子重新启动NA
需要重启NA包括基线HBeAg（+）状态
治疗前（n = 3；复发组50％； n = 5； 12％
非复发组； p = 0 004）和更长的NA治疗
持续时间（复发组中位持续时间12 4年；
非复发组中6 1年，p = 0 011）年龄，性别，肝脏
停止时的僵硬度，NA，种族和qHBsAg水平均未
与复发风险有关我们的数据表明患者
肝病，第72卷，第1号（增补）AASLD摘要（口服）21A
a代表AASLD基金会抽象奖获得者
经历过爆发的人在
停用NA，并且一次爆发的可能性较小
这个时期已经安全结束。结论：长期停止
NA在qHBsAg的HBeAg阴性CHB中是可行的
<100IU / mL，但是可能发生严重的ALT发作
密切随访大多数生化和病毒学研究
在停止治疗的最初6个月内会发生耀斑。