AASLD2016[1842 ♦]血清HBsAg和HBcrAg水平的预测HBeAg阴性干扰素为基

StephenW

1842 ♦
Predictive role of serum HBsAg and HBcrAg levels in
patients with HBeAg-negative chronic hepatitis B treated
with pegylated interferon-based therapy
Natthaya Chuaypen1, Nawarat Posuwan1, Sunchai Payungporn1,
Sombat Treeprasertsuk1, Yasuhito Tanaka2, Yong Poovorawan1,
Pisit Tangkijvanich1; 1Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand; 2Nagoya City University Graduate School
of Medical Sciences, Nagoya, Japan
Background: The role of serum hepatitis B core-related antigen
(HBcrAg) quantification in patients with chronic hepatitis
B (CHB) receiving pegylated interferon (PEG-IFN) remains
unclear. The aim of this study was to determine the predictive
role of serum HBsAg and HBcrAg levels in patients with
HBeAg-negative CHB during PEG-IFN-based therapy. Method:
A total of 121 Thai patients with HBeAg-negative CHB were retrospectively
analyzed. Among these, 62 and 59 patients were
treated with PEG-IFN monotherapy and PEG-IFN plus entecavir
for 48 weeks, respectively. Virological response (VR) was
defined as HBV DNA < 2,000 IU/mL at 48 weeks post treatment.
Paired liver biopsies at weeks 0 and 48 were assessed
for intrahepatic covalently closed circular DNA (cccDNA) by
real-time PCR. HBsAg and HBcrAg levels were analyzed by
automated chemiluminescent immunoassays. HBV genotype
was performed by direct sequencing. Results: The distribution
of genotypes B and C was 19% and 81%, respectively. The
overall VR was 48 (39.7%). There was no difference in VR
between monotherapy and combination therapy (41.9% vs
33.9%, P=0.710). Baseline HBcrAg, but not HBsAg was correlated
with cccDNA (Pearson correlation, r=0.380, P=0.001
and r=0.040, P=0.737, respectively). Changes in HBcrAg and
HBsAg levels during therapy were correlated with the reduction
of cccDNA (r=0.346, P=0.003 and r=0.335, P=0.004,
respectively). At baseline, responders had significantly lower
HBsAg levels than non-responders (3.3 ± 0.4 vs. 3.6 ± 0.5
log10IU/mL, P=0.006), but there were no difference between
groups in terms of HBcrAg (4.2 ± 1.3 vs. 4.3 ± 1.2 log10U/mL,
P=0.782) and cccDNA levels (0.5 ± 1.4 vs. 0.3 ± 1.0 log10
copies/cEq, P=0.591). In addition, responders showed more
rapid decline of both serum markers during and after therapy.
At weeks 4 and 12, the absence of HBsAg decline from baseline
yielded negative predictive values (NPV) of 72.7% and
81.0%, respectively. The corresponding figures for the absence
of HBcrAg decline were 68.4% and 73.5%, respectively.
When both criteria were used together, the NPV of achieving
VR at weeks 4 and 12 were 85.0% and 100%, respectively.
HBsAg decline from baseline ≥0.5 log10IU/mL at week 12
yielded a positive predictive value (PPV) of 77.5%, while the
corresponding figure for HBcrAg decline ≥0.5 log10U/mL was
52.3%. Patients in whom both declines were present had a
PPV of 84.2%. Conclusion: Quantitative HBcrAg represented
a surrogate marker of cccDNA in HBeAg-negative CHB. The
combined use of HBsAg and HBcrAg levels during PEG-IFNbased
therapy could identify patients with high or low probability
of response and may help individualize on-treatment
decision-making.
Disclosures:
Yasuhito Tanaka - Grant/Research Support: Chugai Pharmaceutical CO., LTD.,
MSD, abbvie, Bristol-Myers Squibb; Speaking and Teaching: Bristol-Myers
Squibb
The following people have nothing to disclose: Natthaya Chuaypen, Nawarat
Posuwan, Sunchai Payungporn, Sombat Treeprasertsuk, Yong Poovorawan, Pisit
Tangkijvanich

StephenW

AASLD2016 [1842♦]血清HBsAg和HBcrAg水平的预测HBeAg阴性干扰素为基础的治疗
血清HBsAg和HBcrAg水平的预测作用
HBeAg阴性的慢性乙型肝炎患者治疗
与聚乙二醇化干扰素为基础的治疗
Natthaya Chuaypen1，Nawarat Posuwan1，Sunchai Payungporn1，
Sombat Treeprasertsuk1，Yasuhito Tanaka2，Yong Poovorawan1，
Pisit Tangkijvanich1; 1朱拉隆功大学医学院，
曼谷，泰国; 2Nagoya城市大学研究生院
of Medical Sciences，Nagoya，Japan
背景：血清乙型肝炎核心相关抗原的作用
（HBcrAg）定量在慢性肝炎患者
B（CHB）接受聚乙二醇化干扰素（PEG-IFN）
不清楚。这项研究的目的是确定预测
血清HBsAg和HBcrAg水平在患者中的作用
HBeAg阴性CHB在基于PEG-IFN的治疗期间。方法：
回顾性分析121例泰国HBeAg阴性CHB患者
分析。其中，62例和59例患者
用PEG-IFN单一疗法和PEG-IFN加恩替卡韦治疗
持续48周。病毒学反应（VR）
在治疗后48周定义为HBV DNA <2,000IU / mL。
在第0周和第48周进行配对的肝活组织检查
用于肝内共价闭合环状DNA（cccDNA）
实时PCR。分析HBsAg和HBcrAg水平
自动化学发光免疫测定。 HBV基因型
通过直接测序进行。结果：分布
的基因型B和C分别为19％和81％。的
总体VR为48（39.7％）。 VR没有差别
单一疗法和联合疗法（41.9％vs
33.9％，P = 0.710）。基线HBcrAg，但不是HBsAg是相关的
与cccDNA（Pearson相关，r = 0.380，P = 0.001
和r = 0.040，P = 0.737）。 HBcrAg和
治疗期间的HBsAg水平与减少相关
的cccDNA（r = 0.346，P = 0.003和r = 0.335，P = 0.004，
分别）。在基线时，应答者显着降低
HBsAg水平比无反应者（3.3±0.4对3.6±0.5
log10IU / mL，P = 0.006），但两者无差异
组的HBcrAg（4.2±1.3对4.3±1.2log10U / mL，
P = 0.782）和cccDNA水平（0.5±1.4对0.3±1.0log10
拷贝/ cEq，P = 0.591）。此外，反应者显示更多
治疗期间和治疗后两种血清标志物的快速下降。
在第4周和第12周，HBsAg的缺乏从基线下降
产生72.7％的阴性预测值（NPV）
81.0％。缺席的相应数字
的HBcrAg下降分别为68.4％和73.5％。
当两个标准一起使用时，实现的NPV
第4周和第12周的VR分别为85.0％和100％。
在基线时HBsAg从基线下降≥0.5log10 IU / mL
产生77.5％的阳性预测值（PPV），而
相应的HBcrAg下降≥0.5log10U/ mL的数字
52.3％。患有两种下降的患者都有
PPV为84.2％。结论：定量HBcrAg代表
HBeAg阴性CHB中cccDNA的替代标记。的
在PEG-IFN基础中联合使用HBsAg和HBcrAg水平
治疗可以识别具有高或低概率的患者
的反应，可以帮助个性化治疗
做决定。
披露：
Yasuhito Tanaka - 资助/研究支持：中外制药有限公司，
MSD，abbvie，Bristol-Myers Squibb;口语和教学：Bristol-Myers
Squibb
以下人士没有透露：Natthaya Chuaypen，Nawarat
Posuwan，Sunchai Payungporn，Sombat Treeprasertsuk，Yong Poovorawan，Pisit
Tangkijvanich