EASL 2018 PS-158 HBeAg阴性的HBsAg血清学清除率增加 慢性乙型肝炎

StephenW

EASL 2018 PS-158
Increased incidence of HBsAg seroclearance in HBeAg negative
chronic hepatitis B patients discontinued Nuc therapy comparing
to natural course–a propensity score matched study
W.-J. Jeng1,3,5, H.-I. Yang2,6, Y.-C. Chen1,3,5, J. Liu2,4, R.-N. Chien1,3,5,
I.-S. Sheen1,5, C.-J. Chen2, Y.-F. Liaw3,5. 1Department of Gastroenterology
and Hepatology, Chang Gung Memorial Hospital, Linkou; 2Genomic
Research Center, Academia Sinica; 3College of Medicine, Chang Gung
University; 4Stanford University School od Medicine and Lucile Packard
Children’s Hospital; 5Liver research Unit, Chang Gung Memorial
Hospital, Linkou; 6Institute of Clinical Medicine, National Yang Ming
University
Email: [email protected]
Background and Aims: Hepatitis B s antigen (HBsAg) loss is a rare
event during nucleos(t)ide analogue (Nuc) therapy but may increase
in HBeAg negative chronic hepatitis B patients with sustained
remission during off Nuc follow-up. It is unknown whether the
incidence during and off Nuc is the effect of therapy or just an event of
the natural course of chronic hepatitis B.
Aim: To test whether the incidence of HBsAg seroclearance in HBeAg
negative CHB patients with finite Nuc therapy is higher than that of
subjects in REVEAL natural history cohort.
Method: A total of 762 HBeAg negative CHB patients received finite
Nuc therapy from Chang Gung Memorial Hospital were compared to
2,772 HBeAg negative REVEAL-CHB cohort patients whose baseline
HBV DNA and HBsAg quantification data were available. Propensity
score matching (PSM) on age, gender, cirrhosis, baseline ALT, HBV
DNA and HBsAg (qHBsAg) levels were applied. The Incidence of
HBsAg seroclearance was calculated. Cox regression model was used
for investigating predictors of HBsAg seroclearance after adjustment
for PSM-variables.
Results: Before adjustment, the Nuc-treated cohort showed older
age, greater proportion of male, liver cirrhosis and genotype B, higher
ALT, HBV DNA and qHBsAg levels and shorter follow-up duration.
After 1:1 propensity score matching, there were 262 patients each in
Nuc-treated and REVEAL cohort. The incidence rate of HBsAg
seroclearance in Nuc-treated cohort was 105.637 x 104 person-year
while it was 82.790 x 104 person-year in REVEAL cohort. Kaplan-
Meier analysis showed higher cumulative HBsAg seroclearance rate in
patients with finite Nuc-therapy (p = 0.001). The difference became
more apparent after 6 years of follow-up since the entry of treatment
(treatment duration: mean: 3.1 years). Multivariate Cox regression
analysis showed that lower qHBsAg at entry (>=1000 vs. <1000,
adjusted HR: 0.167(0.072–0.388), p < 0.0001) and patients with finite
Nuc treatment (vs. REVEAL, adjusted HR: 3.41 (1.634–7.116), p =
0.0011) were two independent predictors for HBsAg seroclearance.
Figure: Cumulative HBsAg seroclearance rate of Nuc-treated cohort and
REVEAL cohort after propensity score matching of age, gender, cirrhosis,
baseline HBV DNA, qHBsAg and ALT.
Conclusion: The findings (1) patients with finite Nuc therapy had
significantly higher incidence of HBsAg seroclearance than that
during the natural course of CHB; (2) finite Nuc therapy was an
independent factor for HBsAg seroclearance; indicate that HBsAg
seroclearance in patients with finite Nuc therapy reflects the effect of
therapy rather than just a natural event of HBeAg-negative CHB.

StephenW

EASL 2018 PS-158
HBeAg阴性的HBsAg血清学清除率增加
慢性乙型肝炎患者停止Nuc疗法比较
自然过程 - 倾向分数匹配研究
W.-J. Jeng1,3,5，H.-I. Yang2,6，Y.-C. Chen1,3,5，J.Liu2,4，R.-N. Chien1,3,5，
I.-S. Sheen1,5，C.-J. Chen2，Y.-F. Liaw3,5。 1胃肠病学
林口长庚医院肝病科; 2Genomic
中国科学院研究中心; 3长庚医学院
大学; 4斯坦福大学医学院和露西尔帕卡德
儿童医院; 5长寿纪念馆研究室
林口医院; 6国家临床医学研究所杨明
大学
电子邮件：[email protected]
背景和目标：乙型肝炎抗原（HBsAg）丢失是罕见的
核苷（酸）类似物（Nuc）治疗期间的事件，但可能增加
在HBeAg阴性的慢性乙型肝炎患者中持续存在
在关闭Nuc后续期间缓解。这是否是未知数
Nuc期间和发生的发生率是治疗的效果还是仅仅是发生的事件
慢性乙型肝炎的自然病程
目的：检测HBeAg中HBsAg血清学清除的发生率
有限的Nuc疗法的阴性CHB患者高于
科目在REVEAL自然历史队列。
方法：共有762名HBeAg阴性慢性乙型肝炎患者接受有限的治疗
比较长庚医院的Nuc疗法
2,772名HBeAg阴性REVEAL-CHB队列患者的基线
HBV DNA和HBsAg定量数据可用。倾向
年龄，性别，肝硬化，基线ALT，HBV的评分匹配（PSM）
应用DNA和HBsAg（qHBsAg）水平。事件的发生
计算HBsAg血清清除率。使用Cox回归模型
调查后调查HBsAg血清学清除率的预测因子
用于PSM变量。
结果：调整前，Nuc治疗队列显示年龄较大
年龄越大，男性比例越高，肝硬化和基因型B越高
ALT，HBV DNA和qHBsAg水平以及随访时间缩短。
在1：1倾向评分匹配后，每个患者262人
Nuc治疗和REVEAL队列。 HBsAg的发病率
Nuc治疗队列的血清清除率为105.637×104人年
而在REVEAL队列中则为82.790 x 104人年。卡普兰
Meier分析显示，HBsAg血清学清除率更高
有限Nuc疗法的患者（p = 0.001）。差异变成了
治疗进入后6年的随访更加明显
（治疗时间：平均：3.1年）。多变量Cox回归
分析显示入口处（> = 1000对<1000，
调整HR：0.167（0.072-0.388），p <0.0001）和有限的患者
Nuc治疗（vs. REVEAL，校正后HR：3.41（1.634-7.116），p =
0.0011）是HBsAg血清清除率的两个独立预测因子。
图：Nuc治疗队列的累积HBsAg血清学清除率
REVEAL队列在年龄，性别，肝硬化，
基线HBV DNA，qHBsAg和ALT。
结论：结果（1）有限的Nuc疗法的患者有
HBsAg血清学清除率明显高于此
在CHB的自然过程中; （2）有限的Nuc疗法是
HBsAg血清学清除的独立因素;表明HBsAg
Nuc疗法有限的患者血清清除率反映了有效的Nuc疗法
而不仅仅是HBeAg阴性CHB的自然事件。

Hepbest

EASL 2018 PS-158 Increased incidence of HBsAg seroclearance in HBeAg negative chronic hepatitis B patients discontinued Nuc therapy comparing to natural course–a propensity score matched study W.-J. Jeng1,3,5, H.-I. Yang2,6, Y.-C. Chen1,3,5, J. Liu2,4, R.-N. Chien1,3,5, I.-S. Sheen1,5, C.-J. Chen2, Y.-F. Liaw3,5. 1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou; 2Genomic Research Center, Academia Sinica; 3College of Medicine, Chang Gung University; 4Stanford University School od Medicine and Lucile Packard Children’s Hospital; 5Liver research Unit, Chang Gung Memorial Hospital, Linkou; 6Institute of Clinical Medicine, National Yang Ming University
Email: [email protected]

Background and Aims:
Hepatitis B s antigen (HBsAg) loss is a rare event during nucleos(t)ide analogue (Nuc) therapy but may increase in HBeAg negative chronic hepatitis B patients with sustained remission during off Nuc follow-up. It is unknown whether the incidence during and off Nuc is the effect of therapy or just an event of the natural course of chronic hepatitis B.

Aim:
To test whether the incidence of HBsAg seroclearance in HBeAg negative CHB patients with finite Nuc therapy is higher than that of subjects in REVEAL natural history cohort.

Method:
A total of 762 HBeAg negative CHB patients received finite Nuc therapy from Chang Gung Memorial Hospital were compared to 2,772 HBeAg negative REVEAL-CHB cohort patients whose baseline HBV DNA and HBsAg quantification data were available. Propensity score matching (PSM) on age, gender, cirrhosis, baseline ALT, HBV DNA and HBsAg (qHBsAg) levels were applied. The Incidence of HBsAg seroclearance was calculated. Cox regression model was used for investigating predictors of HBsAg seroclearance after adjustment for PSM-variables.

Results:
Before adjustment, the Nuc-treated cohort showed older age, greater proportion of male, liver cirrhosis and genotype B, higher ALT, HBV DNA and qHBsAg levels and shorter follow-up duration. After 1:1 propensity score matching, there were 262 patients each in Nuc-treated and REVEAL cohort. The incidence rate of HBsAg seroclearance in Nuc-treated cohort was 105.637 x 104 person-year while it was 82.790 x 104 person-year in REVEAL cohort. Kaplan- Meier analysis showed higher cumulative HBsAg seroclearance rate in patients with finite Nuc-therapy (p = 0.001). The difference became more apparent after 6 years of follow-up since the entry of treatment (treatment duration: mean: 3.1 years). Multivariate Cox regression analysis showed that lower qHBsAg at entry (>=1000 vs. <1000, adjusted HR: 0.167(0.072–0.388), p < 0.0001) and patients with finite Nuc treatment (vs. REVEAL, adjusted HR: 3.41 (1.634–7.116), p = 0.0011) were two independent predictors for HBsAg seroclearance.

Figure: Cumulative HBsAg seroclearance rate of Nuc-treated cohort and REVEAL cohort after propensity score matching of age, gender, cirrhosis, baseline HBV DNA, qHBsAg and ALT.

Conclusion:
The findings (1) patients with finite Nuc therapy had significantly higher incidence of HBsAg seroclearance than that during the natural course of CHB; (2) finite Nuc therapy was an independent factor for HBsAg seroclearance; indicate that HBsAg seroclearance in patients with finite Nuc therapy reflects the effect of therapy rather than just a natural event of HBeAg-negative CHB.

Hepbest

EASL 2018 PS-158 HBeAg阴性慢性乙型肝炎患者中HBsAg血清学清除率增加停止Nuc疗法与自然疗法相比 - 倾向评分匹配研究W.-J. Jeng1,3,5，H.-I. Yang2,6，Y.-C. Chen1,3,5，J.Liu2,4，R.-N. Chien1,3,5，I.-S. Sheen1,5，C.-J. Chen2，Y.-F. Liaw3,5。 1林口长庚医院消化科和肝病科;中国科学院2个基因研究中心; 3长庚大学医学院; 4斯坦福大学医学院和露西尔帕卡德儿童医院; 5林口长庚医院肝脏研究室; 6杨明大学临床医学研究所
 电子邮件：[email protected]
 
 背景和目标：
 在核苷（酸）类似物（Nuc）治疗期间乙型肝炎抗原（HBsAg）丧失是罕见事件，但在Nuc随访期间持续缓解的HBeAg阴性慢性乙型肝炎患者中可能增加。目前尚不清楚Nuc的发生率和发病率是治疗效果还是仅仅是慢性乙型肝炎自然发作的事件。
 
 目标：
 为了测试有限Nuc疗法的HBeAg阴性CHB患者中HBsAg血清清除率的发生率是否高于REVEAL自然史队列中的受试者。
 
 方法：
 来自长庚医院的762例HBeAg阴性慢性乙型肝炎患者接受有限的Nuc治疗，与2,772例HBeAg阴性REVEAL-CHB队列患者进行比较，这些患者的基线HBV DNA和HBsAg定量数据可用。应用年龄，性别，肝硬化，基线ALT，HBV DNA和HBsAg（qHBsAg）水平的倾向评分匹配（PSM）。计算了HBsAg血清学清除的发生率。 Cox回归模型用于研究调整PSM变量后HBsAg血清学清除率的预测因子。
 
 结果：
 调整前，Nuc治疗队列显示年龄较大，男性，肝硬化和基因型B的比例较高，ALT，HBV DNA和qHBsAg水平较高，随访时间较短。在1：1倾向评分匹配后，Nuc治疗组和REVEAL组各有262例患者。 Nuc治疗队列中HBsAg血清清除率的发生率为105.637 x 104人年，而REVEAL队列中为82.790 x 104人年。 Kaplan-Meier分析显示Nuc治疗有限的患者累积HBsAg血清清除率更高（p = 0.001）。自治疗进入后6年的随访结果（治疗时间：平均3.1年），差异更加明显。多变量Cox回归分析显示，入组时（> = 1000与<1000，调整后的HR：0.167（0.072-0.388），p <0.0001）和有限的Nuc治疗的患者qHBsAg较低（vs. REVEAL，校正后HR：3.41（1.634 -7.116），p = 0.0011）是HBsAg血清清除的两个独立预测因子。
 
 图：Nuc治疗队列和REVEAL队列在年龄，性别，肝硬化，基线HBV DNA，qHBsAg和ALT倾向评分匹配后的累积HBsAg血清清除率。
 
 结论：
 研究结果（1）有限Nuc疗法的患者HBsAg血清清除率显着高于CHB自然病程; （2）有限的Nuc疗法是HBsAg血清学清除的独立因素;表明有限Nuc疗法的患者HBsAg血清学清除反映了治疗效果，而不仅仅是HBeAg阴性CHB的自然事件。