AASLD2018[2080]通过血清纤维连接蛋白水平鉴定 蛋白质组学分析

StephenW

2080
Serum Fibronectin Levels Identified Via
Proteomics Profiling Predict Spontaneous
Hepatitis B Surface Antigen Seroclearance in
Chronic Hepatitis B
Fen Liu1, Wai Kay Walter Seto2, Danny Ka Ho Wong3,
Fung-Yu Huang1, Lung-Yi Mak4, Ka Shing Cheung1, James
Fung5, Ching Lung Lai1 and Man-Fung Yuen6, (1)Medicine,
The University of Hong Kong, (2)Queen Mary Hospital,
Hong Kong, Hong Kong, (3)State Key Laboratory for Liver
Research, The University of Hong Kong, (4)Queen Mary
Hospital, (5)Medicine, Queen Mary Hospital, (6)Department
of Medicine, University of Hong Kong, Queen Mary Hospital
Background: Seroclearance of hepatitis B surface antigen
(HBsAg) is perceived as the practically ideal treatment
endpoint and “functional cure” of chronic hepatitis B (CHB).
Our previous analysis of isobaric tags for relative and absolute
quantitation (iTRAQ) based proteomics demonstrated
HBsAg seroclearance was associated with overexpression
of serum fibronectin. In this study, we aimed to validate the
predictive value of fibronectin in a large population of CHB
patients with HBsAg seroclearance. Methods: We retrieved
archived serum samples from our previous study comparing
serum HBsAg kinetics between CHB achieving spontaneous
HBsAg seroclearance with age- and sex-matched hepatitis
B e antigen (HBeAg)-negative controls. Serum fibronectin
levels at 3 years (Year -3) and 1 year (Year -1) before HBsAg
seroclearance and at the time of HBsAg seroclearance (Year
0) were assayed using the Human Fibronectin Enzyme-
Linked Immunosorbent Assay (ELISA) kit (ab108848,
Abcam). Association of changes between serum fibronectin
and HBsAg levels were analyzed. Results: In 139 patients
achieving HBsAg seroclearance and with available archived
serum, the mean age was 52.3±11.1 years (66.2% male),
of which 38 (27.3%) patients had developed anti-HBs. The
median HBsAg level in HBeAg-negative control group
(n=139) was 2.55 log (interquartile range (IQR): 1.28-3.32)
IU/mL. At Year 0, patients achieving HBsAg seroclearance
had lower median HBV DNA levels when compared to
controls (1.36±0.21log IU/ml vs. 3.16±1.37 log IU/ml, P
<0.001). At both year -1 and year 0, patients who achieved
spontaneous HBsAg seroclearance had significantly higher
median fibronectin levels than that of the controls (331.57
μg/ml vs. 226.97 μg/ml; 432.02 μg/ml vs. 281.14 μg/ml, both
P <0.001, respectively). The levels of fibronectin at Year -3
were comparable in the two groups. In patients with an annual
HBsAg log reduction >1 (n=68), serum fibronectin level at
Year -1, when compared to matched controls, achieved an
area under the receiving operator characteristic (AUROC) of
0.789 (95% confidence interval [CI]: 0.575-1.000; P=0.038)
in predicting HBsAg seroclearance. The optimal cut-off
fibronectin level for predicting HBsAg seroclearance was
210.52 μg/ml. Conclusion: Higher serum fibronectin level
one year prior to HBsAg seroclearance were associated
with subsequent HBsAg seroclearance. Combining serum
fibronectin level with the degree of HBsAg reduction may act
as novel predictors for HBsAg seroclearance. Exploration
of the pathophysiological role of fibronectin on HBsAg
seroclearance is needed in future studies.

StephenW

2080
通过血清纤维连接蛋白水平鉴定
蛋白质组学分析预测自发性
乙型肝炎表面抗原血清清除率
慢性乙型肝炎
Fen Liu1，Wai Kay Walter Seto2，Danny Ka Ho Wong3，
黄凤玉1，龙义懿4，嘉诚祥1，詹姆斯
Fung5，Ching Lung Lai1和Man-Fung Yuen6，（1）医学，
香港大学，（2）玛丽医院，
香港，香港，（3）肝脏国家重点实验室
研究，香港大学，（4）玛丽女王
医院，（5）医学，玛丽医院，（6）科
香港大学医学院玛丽医院
背景：乙型肝炎表面抗原的血清清除率
（HBsAg）被认为是实际上理想的治疗方法
终点和慢性乙型肝炎（CHB）的“功能性治愈”。
我们之前对相对和绝对等压标签的分析
基于定量（iTRAQ）的蛋白质组学证明了这一点
HBsAg血清清除与过度表达有关
血清纤维连接蛋白在这项研究中，我们旨在验证
纤维连接蛋白在大量CHB中的预测价值
HBsAg血清清除的患者。方法：我们检索
来自我们之前研究的存档血清样本比较
CHB达到自发性血清的血清HBsAg动力学
HBsAg血清清除与年龄和性别匹配的肝炎
B e抗原（HBeAg） - 阴性对照。血清纤维连接蛋白
HBsAg前3年（第-3年）和1年（第-1年）的水平
血清清除和HBsAg血清清除时（年
0）使用人纤连蛋白酶测定 -
连接免疫吸附测定（ELISA）试剂盒（ab108848，
Abcam公司）。血清纤维连接蛋白变化的关联
和HBsAg水平进行了分析。结果：139例患者
实现HBsAg血清清除和可用存档
血清，平均年龄为52.3±11.1岁（男性占66.2％），
其中38例（27.3％）患者已发生抗-HBs。该
HBeAg阴性对照组HBsAg中位数水平
（n = 139）为2.55 log（四分位距（IQR）：1.28-3.32）
IU /毫升。在0年级，患者达到HBsAg血清清除率
与...相比，HBV DNA中位数水平较低
对照组（1.36±0.21log IU / ml对比3.16±1.37 log IU / ml，P
<0.001）。在第-1年和第0年，患者取得了成功
自发性HBsAg血清清除率明显升高
中位纤连蛋白水平高于对照组（331.57
μg/ ml对226.97μg/ ml;两者均为432.02μg/ ml，相对于281.14μg/ ml
分别为P <0.001）。第-3年的纤连蛋白水平
在两组中具有可比性。患者每年一次
HBsAg对数减少> 1（n = 68），血清纤连蛋白水平为
第-1年，与匹配的对照相比，达到了
接收运营商特征（AUROC）下的区域
0.789（95％置信区间[CI]：0.575-1.000; P = 0.038）
预测HBsAg血清清除率。最佳截止
用于预测HBsAg血清清除率的纤维连接蛋白水平为
210.52μg/ ml。结论：血清纤维连接蛋白水平升高
HBsAg血清清除前一年相关
随后HBsAg血清清除。结合血清
纤维连接蛋白水平与HBsAg降低程度有关
作为HBsAg血清清除的新型预测因子。勘探
纤维连接蛋白对HBsAg的病理生理作用
在未来的研究中需要血清清除。