AASLD2020[158]治疗结束HBsAg，HBCRAG和HBV RNA水平 预测患者非治疗

StephenW

158
END OF TREATMENT HBsAg, HBCRAG AND HBV RNA LEVELS
PREDICT RISK OF OFF-TREATMENT ALT FLARES IN PATIENTS
WITH CHRONIC HEPATITIS B.
Sylvia Brakenhoff1, Robert J. De Knegt2, Margo Van
Campenhout1, Annemiek A. Van Der Eijk3, Willem Pieter
Brouwer4, Florian Van Bömmel5, Andre Boonstra4, Bettina
E. Hansen6,7, Thomas Berg5, Harry L.A. Janssen8, Robert
A. De Man1 and Milan J. Sonneveld1, (1)Department of
Gastroenterology and Hepatology, Erasmus MC, University
Medical Center, (2)Department of Gastroenterology and
Hepatology, Erasmus University Medical Center Rotterdam,
(3)Department of Viroscience, Erasmus MC, University
Medical Center, (4)Department of Gastroenterology and
Hepatology, Erasmus University Medical Center, (5)Division
of Hepatology, Department of Medicine II, Leipzig University,
Medical Center, Leipzig, Germany, (6)Toronto Center for Liver
Disease, UHN & Ihpme University of Toronto, (7)Institute
of Health Policy, Management and Evaluation, University
of Toronto, (8)Toronto Centre for Liver Disease, University
Health Network
Background: Since ALT flares after therapy withdrawal are
associated with adverse outcomes, risk stratification is of
major clinical importance We aimed to study whether serum
levels of novel biomarkers at end of treatment (EOT) are
associated with occurrence of off-treatment flares. Methods:
We studied chronic hepatitis B patients who participated in
three global randomized trials of peginterferon-based therapy
(99-01 [PEG-IFN alone vs PEG-IFN + lamivudine], PARC
[PEG-IFN alone vs PEG-IFN with ribavirin] and ARES [ETV
with PEG-IFN add-on]) HBV RNA, HBsAg and hepatitis
B core related antigen (HBcrAg) were quantified at EOT.
Associations between biomarker levels and ALT flares were
assessed using continuous data and after categorization
(<3/>3 log for HBsAg, undetectable/detectable for HBV RNA,
and for HBcrAg <3/>3 log for HBeAg-negative and <6/>6 log
for HBeAg-positive patients) SCALE-B score (comprising
HBsAg, HBcrAg, age and ALT) was also calculated and
patients were categorized using previously reported cut-offs
(<260 , 260-320, >320). ALT flares were defined as an ALT
≥5x ULN during the first 6 months after therapy cessation.
Analyses were performed in the overall cohort, and in the
subgroup of patients with an EOT response (defined as
HBeAg negativity with HBV DNA <200 IU/mL) Results:
A total of 344 patients with EOT data were enrolled; 230
HBeAg-positive and 114 HBeAg-negative Patients were
predominantly Caucasian (77 0%) and had genotype A/B/C/D
in 23 3/7 3/13 4/52 3% An EOT response was observed in
120 patients (34 9%) During follow-up, 122 patients (35 5%)
experienced an ALT flare. Higher HBsAg (OR 1.586, 95% CI
1 231-2 043, p<0 001), HBV RNA (OR 1 695, 95% CI: 1 371-
2 094, p<0 001) and HBcrAg (OR 1 518 95% CI: 1 324-1 740,
p<0 001) levels at EOT were associated with higher risks of
ALT flares (figure 1). Combinations of biomarkers, e.g. HBV
RNA with HBsAg or the SCALE-B score, further improved risk
stratification: for example, among 69 patients with both high
HBV RNA and HBsAg levels, 36 (52.2%) experienced a flare,
compared to 0/42 patients (0 0%) with low HBV RNA and
HBsAg levels (p<0.001, figure 1). Findings were consistent
across pre-treatment HBeAg-positive and -negative patients
and in the patients with an EOT response Conclusion:
Higher EOT serum HBsAg, HBcrAg and HBV RNA levels
are associated with a higher risk of ALT flares after therapy
withdrawal. These findings can be used to guide decisionmaking
regarding therapy discontinuation and intensity of
off-treatment follow-up Figure 1. Rates of off-treatment
flares (ALT ≥5x ULN) in the overall cohort, according to
HBsAg, HBcrAg and HBV RNA levels at end of treatment.

StephenW

158
治疗结束HBsAg，HBCRAG和HBV RNA水平
预测患者非治疗性ALT的风险
患有慢性肝炎B.
西尔维亚·布拉肯霍夫（Sylvia Brakenhoff）1，罗伯特·J·德·克奈特（Robert J.
Campenhout1，Annemiek A.Van Der Eijk3，Willem Pieter
Brouwer4，Florian VanBömmel5，Andre Boonstra4，Bettina
E. Hansen6,7，Thomas Berg5，Harry L.A. Janssen8，Robert
A.De Man1和Milan J.Sonneveld1，（1）
胃肠病学和肝病学，伊拉斯姆斯大学
医学中心（2）消化内科
鹿特丹伊拉斯姆斯大学医学中心肝病科
（3）大学Erasmus MC，病毒科学系
医学中心，（4）消化内科
伊拉斯姆斯大学医学中心肝病科（5）
莱比锡大学第二医学系肝病科，
德国莱比锡医学中心，（6）多伦多肝病中心
UHN和Ihpme多伦多大学疾病研究所（7）
大学卫生政策，管理与评估学院
多伦多大学（8）多伦多大学肝病中心
健康网
背景：由于停药后的ALT发作是
与不良后果相关的风险分层是
主要临床意义我们旨在研究血清是否
治疗结束时（EOT）的新型生物标志物水平为
与处理后耀斑的发生有关。方法：
我们研究了参与研究的慢性乙型肝炎患者
基于聚乙二醇干扰素治疗的三项全球随机试验
（99-01 [单独使用PEG-IFN与PEG-IFN +拉米夫定]，PARC
[单独的PEG-IFN与带有病毒唑的PEG-IFN]和ARES [ETV
含PEG-IFN的药物]）HBV RNA，HBsAg和肝炎
B核心相关抗原（HBcrAg）在EOT时定量。
生物标志物水平和ALT耀斑之间的关联是
使用连续数据和分类后进行评估
（对于HBsAg，<3 /> 3 log，对于HBV RNA，不可检测/可检测，
HBcrAg阴性的HBcrAg <3 /> 3 log和<6 /> 6的log
对于HBeAg阳性患者）SCALE-B评分（包括
还计算了HBsAg，HBcrAg，年龄和ALT），
使用先前报告的临界值对患者进行分类
（<260、260-320，> 320）。 ALT耀斑定义为ALT
停止治疗后的前6个月，ULN≥5x。
在整个队列中以及在
EOT反应的患者亚组（定义为
HBV DNA <200 IU / mL的HBeAg阴性）结果：
共有344例具有EOT数据的患者入选； 230
HBeAg阳性和114例HBeAg阴性的患者
主要是白种人（77 0％），且具有A / B / C / D基因型
在23 3/7 3/13 4/52 3％中观察到EOT响应
120位患者（34 9％）随访期间，122位患者（35 5％）
经历了ALT爆发。 HBsAg更高（OR 1.586，95％CI
1 231-2 043，p <0001），HBV RNA（或1695，95％CI：1371-
2094，p <0.0001）和HBcrAg（OR 1518 95％CI：1324-1740，
EOT时的p <0 001）水平与较高的
ALT耀斑（图1）。生物标志物的组合，例如乙肝病毒
具有HBsAg或SCALE-B评分的RNA，可进一步降低风险
分层：例如，在69例
HBV RNA和HBsAg水平有36（52.2％）发生了耀斑，
与0/42例HBV RNA低和（0 0％）的患者相比
HBsAg水平（p <0.001，图1）。调查结果是一致的
治疗前HBeAg阳性和阴性患者
并有EOT反应的患者结论：
EOT血清HBsAg，HBcrAg和HBV RNA水平较高
与治疗后发生ALT耀斑的风险较高相关
退出。这些发现可用于指导决策
关于治疗中止和强度
图1.停药率
总体队列中的耀斑（ALT≥5倍ULN）
治疗结束时HBsAg，HBcrAg和HBV RNA水平。