AASLD2020[805]治疗性耀斑与快速HBV相关 基于聚乙二醇干扰素的RN

StephenW

805
ON-TREATMENT FLARES ARE ASSOCIATED WITH RAPID HBV
RNA AND HBsAg DECLINE DURING PEGYLATED INTERFERONBASED
THERAPY FOR CHRONIC HBV INFECTION
Hannah S.J. Choi1,2, Milan J. Sonneveld3, Mina S. Farag2,
Willem Pieter Brouwer4, Grishma Hirode2, Adam J. Gehring2,
Robert A. De Man4, Bettina E. Hansen5,6 and Harry L.A.
Janssen2, (1)Institute of Medical Science, University of
Toronto, (2)Toronto Centre for Liver Disease, University
Health Network, (3)Erasmus University Medical Center, (4)
Department of Gastroenterology and Hepatology, Erasmus
University Medical Center, (5)Institute of Health Policy,
Management and Evaluation, University of Toronto, (6)
Toronto Centre for Liver Disease/Viral Hepatitis Care Network
(VIRCAN), University Health Network
Background: As pegylated interferon-alpha (PEG-IFN-α) is
increasingly used in combination regimens of novel drugs to
achieve a functional cure, we aimed to characterize flares and
their relationship with serum HBsAg and HBV RNA kinetics in
a large combined cohort of chronic hepatitis B (CHB )patients
on pegylated interferon-alpha (PEG-IFN-α)-based therapy.
Methods: In this post hoc analysis of four international
randomized trials, 269 patients on PEG-IFN-α monotherapy,
130 on PEG-IFN-α plus nucleos(t)ide analogue (NA) de novo
combination, 124 on PEG-IFN-α add-on to NA, and 128 on
NA monotherapy were included. A flare was defined as an
episode of ALT elevation ≥5×ULN. The association between
flares and serum HBsAg and HBV RNA changes during
treatment and at the final visit were examined. Results:
On-treatment flares occurred in 83/651 (13%) patients. The
median timing of the first flare was week 8 (IQR 4-12) and the
median magnitude was 7 9×ULN (IQR 6 2-11 6) Flares were
more frequent in Caucasians and those with higher baseline
ALT, HBV DNA, HBV RNA, and HBsAg levels compared to
the no-flare group (all P<0.01). More flares were observed
in the PEG-IFN-α monotherapy (18%) and PEG-IFN+NA de
novo combination (24%) versus PEG-IFN-α add-on (2%) or
NA monotherapy (1%) groups (Figure; P<0 01) On-treatment
flares were significantly and independently associated
with HBsAg and HBV RNA decline ≥1 log10 at the final visit
(adjusted odds ratio: 4 8 [95% CI 2 6-8 6], P<0 01, and 1 9
[1 1-3 3], P=0 02, respectively); declines started from 12
weeks before the flare, progressing toward 24 weeks after.
On-treatment flares were seen in 16/22 (73%) patients who
achieved HBsAg loss. Post-PEG-IFN-α flares occurred in
41 patients during 6 months of follow-up but did not result
in HBsAg loss; 3/41 (7%) achieved HBsAg decline ≥1 log10
at the final visit. Post-PEG-IFN-α flares were not associated
with HBsAg and/or HBV RNA decline Conclusion: Flares
occurring during PEG-IFN-α treatment were associated with
subsequent HBsAg and HBV RNA decline and HBsAg loss,
suggesting a robust antiviral immune response Using PEGIFN-
α and targeting the window of heightened response with
new antiviral agents may be effective in achieving a functional
cure of chronic HBV infection.

StephenW

805
治疗性耀斑与快速HBV相关
基于聚乙二醇干扰素的RNA和HBsAg下降
慢性HBV感染的治疗
汉娜·S·J。 Choi1,2，Milan J. Sonneveld3，Mina S. Farag2，
Willem Pieter Brouwer4，Grishma Hirode2，Adam J.Gehring2，
罗伯特·A·德曼（Robert A.De Man4），贝蒂娜·E·汉森（Bettina E.Hansen）5,6和哈里·洛杉矶（Harry L.A.
Janssen2，（1）University of University医学研究所
多伦多大学（2）多伦多肝病中心
卫生网络，（3）伊拉斯姆斯大学医学中心，（4）
伊拉斯mus胃肠病学和肝病学系
大学医学中心（5）卫生政策研究所，
多伦多大学管理与评估，（6）
多伦多肝病/病毒性肝炎护理中心
（VIRCAN），大学健康网
背景：聚乙二醇化干扰素-α（PEG-IFN-α）为
越来越多地用于新药的联合疗法中
实现功能性治愈，我们旨在表征耀斑和
与血清HBsAg和HBV RNA动力学的关系
大量的慢性乙型肝炎（CHB）患者组合
基于聚乙二醇化干扰素-α（PEG-IFN-α）的治疗。
方法：在本次事后分析中，对四个国际
269名接受PEG-IFN-α单药治疗的患者的随机试验，
从头开始在PEG-IFN-α上加上130核苷酸类似物（NA）
组合，在NA上的PEG-IFN-α上有124个，在128个上有128个
不适用单药治疗。耀斑被定义为
ALT升高≥5×ULN发作。之间的关联
发作期间血脂和血清HBsAg和HBV RNA变化
治疗和最终访视时进行了检查。结果：
83/651（13％）患者发生了治疗中的耀斑。的
第一次耀斑的中位时间是第8周（IQR 4-12），
中位数为7 9×ULN（IQR 6 2-11 6）
高加索人和基线较高的人更频繁
与相比，ALT，HBV DNA，HBV RNA和HBsAg水平
无眩光组（所有P <0.01）。观察到更多的耀斑
PEG-IFN-α单药治疗（18％）和PEG-IFN + NA de
新组合（24％）与PEG-IFN-α附加组合（2％）或
NA单药治疗（1％）组（图； P <0 01）正在治疗
耀斑显着且独立相关
最终访视时HBsAg和HBV RNA下降≥1log10
（调整后的赔率：4 8 [95％CI 2 6-8 6]，P <0 01和1 9
[1 1-3 3]，P = 0 02）；下降从12开始
爆发前几周，直到24周后才发展。
在16/22（73％）的患者中观察到治疗中的耀斑
HBsAg丢失。发生PEG-IFN-α后耀斑
随访6个月有41例患者，但未见结果
HBsAg丢失； 3/41（7％）的HBsAg下降≥1log10
在最后一次访问时。 PEG-IFN-α后耀斑不相关
与HBsAg和/或HBV RNA下降结论：耀斑
发生在PEG-IFN-α治疗期间与
随后的HBsAg和HBV RNA下降以及HBsAg丢失，
提示使用PEGIFN-α可以产生强大的抗病毒免疫反应
α并以
新的抗病毒药物可能有效地实现了功能
治愈慢性HBV感染。