AASLD2018[2100]乙型肝炎核心相关抗原相关 含有几种乙型肝炎病

StephenW

2100
Hepatitis B Core Related Antigen Is Correlated
with Several Hepatitis B Virus Markers Including
Serum HBV RNA and Intrahepatic Cccdna.
Robin Erken, Gastroenterology, Academic Medical Centre
Amsterdam, Hans L Zaaijer, Virology, Academic Medical
Centra Amsterdam, Ed Bakker, Sanquin, Neeltje Kootstra,
Experimental Immunology, Academic Medical Centre
Amsterdam and Hendrik W. Reesink, University of Amsterdam
Background: Hepatitis B viral closed circular DNA (cccDNA)
is located in the nucleus of the hepatocyte and can only be
extracted and determined from liver biopsy material. Since
various HBV direct acting antiviral compounds are under
development for functional and total cure, it is important to
establish validated tests that reflect the intrahepatic viral
replicative activity the liver of chronic hepatitis B (CHB)
patients. Hepatitis B core-related antigen (HBcrAg) has
recently been reported as a new serum marker that reflects
intrahepatic cccDNA. Other markers of HBV replication are
HBV-DNA, HBsAg and HBV-RNA. For HBV-RNA commercial
test are currently unavailable. Aim: To investigate the
correlation between HBcrAg and cccDNA and HBV-DNA from
liver tissue and HBV-DNA, HBV-RNA and HBsAg of serum
or plasma from CHB patients. Methods: Baseline serum
or plasma samples as well as liver tissue were available
of 88 CHB patients that were treated with Peg interferon
and Adefovir in a prospective clinical study as described
previously. HBcrAg levels were measured in serum or plasma
at baseline with a lower limit of detection of 3 log10U/mL.
These HBcrAg levels were compared to intrahepatic cccDNA
and HBV DNA levels as well as serum levels of HBsAg, HBV
DNA, and HBV RNA from corresponding samples. Also the
HBeAg status of the patients was established. Comparisons
were made using the Mann-Whitney U test and Spearman
correlation test, correlation coefficient (CC) values were
given. Results: HBcrAg serum levels were median 5.9 log10
U/mL (IQR 4.5-8.0). Of all patients HBcrAg level correlated
well with the serum markers: HBsAg (CC 0.57, p<0.001), HBV
DNA (CC 0.82, p<0.001), HBV RNA (cc 0.84, p<0.001) as well
as with intrahepatic cccDNA (cc 0.78, p<0.001) and HBV DNA
(cc 0.75, p<0.001). HBcrAg levels of HBeAg positive patients
(median 8.0, IQR 6.6-8.4 log10U/mL) were significantly higher
(p> 0.001) than those of HBeAg negative patients (median
4.7, IQR 4.1-5.6 log10U/mL). When analyzing the patients
according to HBeAg status, similar results were obtained
for serum HBV DNA and RNA and intrahepatic cccDNA and
HBV-DNA. However HBsAg was correlated with HBcrAg
only in HBeAg positive patients and not in HBeAg negative
patients (table). Conclusion: HBcrAg levels were strongly
correlated with intrahepatic levels of cccDNA and HBV-DNA
and with serum/plasma HBV DNA and RNA. HBsAg was only
correlated with HBcrAg in HBeAg positive but not in negative
patients.

StephenW

2100
乙型肝炎核心相关抗原相关
含有几种乙型肝炎病毒标记物
血清HBV RNA和肝内Cccdna。
Robin Erken，消化内科，学术医学中心
阿姆斯特丹，Hans L Zaaijer，病毒学，学术医学
Centra Amsterdam，Ed Bakker，Sanquin，Neeltje Kootstra，
实验免疫学，学术医学中心
阿姆斯特丹和Hendrik W. Reesink，阿姆斯特丹大学
背景：乙型肝炎病毒闭合环状DNA（cccDNA）
位于肝细胞的细胞核中，只能是
从肝脏活组织检查材料中提取和确定。以来
各种HBV直接作用的抗病毒化合物都在
功能和完全治愈的发展，重要的是
建立反映肝内病毒的经过验证的测试
复制活动慢性乙型肝炎（CHB）的肝脏
耐心。乙型肝炎核心相关抗原（HBcrAg）有
最近有报道称这是一种新的血清标志物
肝内cccDNA。 HBV复制的其他标志物是
HBV-DNA，HBsAg和HBV-RNA。用于HBV-RNA商业化
测试目前无法使用。目标：调查
HBcrAg与cccDNA和HBV-DNA的相关性研究
肝组织和HBV-DNA，HBV-RNA和血清HBsAg
来自CHB患者的血浆或血浆。方法：基线血清
或血浆样本以及肝脏组织可用
用Peg干扰素治疗的88例CHB患者
和Adefovir在一项前瞻性临床研究中描述
先前。在血清或血浆中测量HBcrAg水平
在基线时检测下限为3 log10U / mL。
将这些HBcrAg水平与肝内cccDNA进行比较
和HBV DNA水平以及血清HBsAg，HBV水平
来自相应样品的DNA和HBV RNA。也是
建立患者的HBeAg状态。比较
是使用Mann-Whitney U测试和Spearman制作的
相关性测试，相关系数（CC）值
给出。结果：HBcrAg血清水平中位数为5.9 log10
U / mL（IQR 4.5-8.0）。在所有患者中HBcrAg水平相关
血清标志物：HBsAg（CC 0.57，p <0.001），HBV
DNA（CC 0.82，p <0.001），HBV RNA（cc 0.84，p <0.001）
与肝内cccDNA（cc 0.78，p <0.001）和HBV DNA一样
（cc 0.75，p <0.001）。 HBeAg水平的HBeAg阳性患者
（中位数8.0，IQR 6.6-8.4 log10U / mL）显着升高
（p> 0.001）比HBeAg阴性患者（中位数
4.7，IQR 4.1-5.6 log10U / mL）。在分析患者时
根据HBeAg状态，获得了类似的结果
用于血清HBV DNA和RNA以及肝内cccDNA和
HBV-DNA。然而，HBsAg与HBcrAg相关
仅在HBeAg阳性患者中且不在HBeAg阴性患者中
患者（表）。结论：HBcrAg水平强烈
与肝内cccDNA和HBV-DNA水平相关
和血清/血浆HBV DNA和RNA。 HBsAg只是
与HBeAg阳性但不是阴性的HBcrAg相关
患者。