AASLD2019[196]慢性乙型肝炎携带者的HBsAg丢失 取决于QHBSAG和干扰

StephenW

196
HBsAg LOSS IN INACTIVE CHRONIC HEPATITIS B CARRIERS
IS DEPENDENT ON LEVEL OF QHBSAG AND INTERFERON
RESPONSE: A RANDOMISED CONTROL TRIAL
Seng Gee Lim1,2,3, Guan Huei Lee4, Yock Young Dan5,
Yin Mei Lee4, Poh Seng Tan2, Wah Wah Phyo3, Htet Htet
Toe Wai Khine3, Karen De Lunas4, Chris Lee3, Amy Tay3,
Cindy Seah6 and Edwin Chan7,8, (1)Gastroenterology &
Hepatology, National University Health System, (2)Division
of Gastroenterology and Hepatology, National University
Health System, Singapore, (3)Dept of Medicine, Yong Loo
Lin School of Medicine, (4)Division of Gastroenterology &
Hepatology, National University Health System, (5)Division
of Gastroenterology & Hepatology, National University
Health System, Singapore, (6)Division of Gastroenterology
and Hepatology, National University Health System, (7)
Epidemiology, Singapore Clinical Research Institute, (8)
Duke-Nus School of Medicine
Background: Retrospective analysis of peginterferon therapy
of Chronic Hepatitis B (CHB) carriers suggests a high rate of
HBsAg loss, but this has not been examined in a prospective
randomised control trial(RCT) Methods: We conducted a three
arm RCT of peginterferon alpha2a (PEG)(pegasys, Roche)
180mcg weekly randomised 1:1:1 to 24 weeks(PEG24), 48
weeks(PEG48) or no treatment(C) in CHB carriers in a single
centre study (clinicaltrials.gov:NCT02992704). Patients were
randomly assigned by computer generated code based
on: HBsAg(+)>6months, HBeAg(-), normal ALT, HBV DNA
≤2x104IU/ml or qHBsAg≤1000IU/ml; absence of cirrhosis,
treatment naive, absence of HCV/HDV/HIV coinfection. The
primary endpoint was HBsAg loss 24weeks after treatment,
and study size of 90 patients had 80% power to detect a 25%
difference between any PEG arm and control Data analysis
was performed using SPSSv20 based on ITT analysis
Baseline and on-treatment variables and multivariate
analysis were used to predict HBsAg loss Results: Baseline
characteristics were similar between groups HBsAg loss
occurred in a total of 7/30 (23 3%) in PEG48, 9/30 (30%) in
PEG24 and 1/30(3 3%) in C Baseline predictors of HBsAg
loss at end-of-interferon treatment showed that qHBsAg
<71IU/ml had an AUROC 0 883; when baseline and ontreatment
predictors were assessed by multivariate analysis,
baseline qHBsAg logIU/ml (OR 10 82, 95%CI 1 02-114 58)
and >1log reduction in qHBsAg at week 12 (OR 11.29, 95%
CI 1 48-86 33) were the strongest predictors of HBsAg loss
There were three distinct patterns of interferon response
despite qHBsAg<71IU/ml: Responders (HBsAg loss) had a
mean qHBsAg log IU/ml reduction at week 24 of 1 46, partial
responders had mean qHBsAg log IU/ml reduction of 0 65
non-responders had mean qHBsAg log IU/ml increase at
week 24 of 0 1 There were a total of 282 adverse events
most of which were interferon related(90%) There were 4
Serious Adverse Events where one was related to treatment
due to hospitalisation from hypothyroidism related to
interferon There were no deaths in the study Conclusion:
HBsAg loss with PEG in inactive carriers leads to 20-30%
HBsAg loss but interferon responsiveness was the main
factor driving HBsAg loss in low qHBsAg patients This has
implications for new immunomodulator therapies that rely on
interferon responsiveness such as TLR7, TLR8 and RIG-I
agonists.

StephenW

196
慢性乙型肝炎携带者的HBsAg丢失
取决于QHBSAG和干扰素的水平
响应：随机控制试验
Seng Gee Lim1,2,3，Guan Huei Lee4，Yock Young Dan5，
李贤美4，保成坛2，华华Ph3，Htet Htet
Toe Wai Khine3，Karen De Lunas4，Chris Lee3，Amy Tay3，
辛迪·西（Cindy Seah）6和埃德温·陈（Edwin Chan）7,8，（1）胃肠病学与
国立大学卫生系统肝病科（2）
国立大学胃肠病学和肝病学
新加坡卫生系统（3）医学部Yong Loo
林医学院，（4）肠胃科
国立大学卫生系统肝病科（5）
国立大学胃肠病学和肝病学
新加坡卫生系统，（6）肠胃科
国立大学卫生系统和肝病学，（7）
新加坡临床研究所流行病学，（8）
杜克努斯医学院
背景：聚乙二醇干扰素治疗的回顾性分析
的慢性乙型肝炎（CHB）携带者表明
HBsAg丢失，但是尚未在前瞻性研究中进行检查
随机对照试验（RCT）方法：我们进行了三项
聚乙二醇干扰素α2a（PEG）的手臂RCT（pegasys，Roche）
每周180mcg随机1：1：1至24周（PEG24），48
单个CHB携带者一周（PEG48）或不进行任何治疗（C）
中心研究（clinicaltrials.gov:NCT02992704）。患者是
根据计算机生成的代码随机分配
开：HBsAg（+）> 6个月，HBeAg（-），正常ALT，HBV DNA
≤2x104IU/ ml或qHBsAg≤1000IU/ ml;没有肝硬化，
天真的治疗，没有HCV / HDV / HIV合并感染。的
主要终点是治疗后24周的HBsAg丢失，
90名患者的研究规模具有80％的力量可以检测25％
任何PEG臂与对照之间的差异数据分析
是根据ITT分析使用SPSSv20执行的
基线和治疗中变量以及多变量
分析用于预测HBsAg丢失结果：基线
组间HBsAg丢失的特征相似
发生在PEG48中的总数为7/30（23 3％），在PEG9中为9/30（30％）
PEG24和HBsAg的C基线预测指标的1/30（3 3％）
干扰素治疗结束后的丢失表明qHBsAg
<71IU / ml的AUROC 0 883;当基线和治疗时
预测因素通过多变量分析进行评估，
基线qHBsAg logIU / ml（OR 10 82，95％CI 1 02-114 58）
在第12周时，qHBsAg降低了> 1log（或11.29，95％
CI 1 48-86 33）是HBsAg丧失的最强预测因子
干扰素反应有三种不同的模式
尽管qHBsAg <71IU / ml：应答者（HBsAg丢失）
在1 46的第24周时平均qHBsAg log IU / ml减少，部分
应答者的平均qHBsAg log IU / ml降低0 65
无反应者的qHBsAg log IU / ml平均增加
0第24周（共1周）共发生282次不良事件
大部分与干扰素有关（90％）有4
与治疗有关的严重不良事件
由于因甲状腺功能减退而住院
干扰素研究中没有死亡结论：
PEG在无活性载体中导致HBsAg丢失导致20-30％
HBsAg丢失，但干扰素反应性是主要因素
低qHBsAg患者中导致HBsAg丢失的因素
依赖于新的免疫调节剂疗法的意义
干扰素反应性，例如TLR7，TLR8和RIG-I
激动剂。