AASLD2018[2077]乙型肝炎核心相关抗原是更好的 标记比HBsAg之间

StephenW

s 2077
Hepatitis B Core-Related Antigen Is a Better
Marker Than HBsAg for Discriminating between
Chronic HBV Infection and Chronic Hepatitis B
in a HBeAg-negative European Cohort.
Maurizia R. Brunetto1, Ivana Carey2, Benjamin Maasoumy3,
Cristina Marcos4, Gijs Van Halewijn5, Gian Paolo Caviglia6,
Alessandro Loglio7, Daniela Cavallone8, Caroline Scholtes9,
Antonina Smedile10, Mar Riveiro-Barciela11, Florian van
Bömmel12, Annemiek Van Der Eijk13, Fabien Zoulim9,
Thomas Berg14, Markus Cornberg15, Pietro Lampertico16,
Kosh Agarwal17 and Maria Buti18, (1)Hepatology Unit
and Laboratory of Molecular Genetics and Pathology of
Hepatitis Viruses, University of Pisa, Italy, (2)Institute of
Liver Studies, King’s College Hospital, (3)Department of
Gastroenterology,Hepatology and Endocrinology, Hannover
Medical School, Hannover, Germany, (4)Liver Unit, Hospital
Universitari Vall D’hebron, Barcelona, Spain, (5)Department
of Viroscience, Erasmus MC University Medical Center, (6)
Department of Medical Sciences, University of Turin, Turin,
Italy, (7)Division of Gastroenterology and Hepatology,
Fondazione Irccs Cà Granda Ospedale Maggiore Policlinico,
Università Degli Studi Di Milano, Italy, (8)Hepatology Unit,
University Hospital of Pisa, (9)Department of Hepatology,
Croix Rousse Hospital, Hospices Civils De Lyon, France,
(10)Department of Medical Sciences, University of Turin,
Italy, (11)Liver Unit, Vall D’hebron University Hospital,
Barcelona, Spain, (12)Hepatology Section, Department of
Gastroenterology and Rheumatology, University Hospital
Leipzig, Germany, (13)Department of Viroscience, Erasmus
MC University Medical Center Rotterdam, Netherlands, (14)
Department of Gastroenterology and Rheumatology, Section
of Hepatology, University Hospital Leipzig, (15)Department
of Gastroenterology, Hepatology and Endocrinology,
Hannover Medical School, Hannover,Germany, (16)Division
of Gastroenterology and Hepatology, Fondazione Irccs Ca’
Granda Ospedale Maggiore Policlinico, Università Degli Studi
Di Milano, Milan, Italy, (17)Institute of Liver Studies, King’s
College Hospital NHS Trust, (18)Liver Unit, Vall D´Hebron
University Hospital, Barcelona, Spain
Background: The natural history of chronic hepatitis B
infection is characterized by multiple phases of host-virus
interplay and the knowledge on the phase is necessary for
making treatment decisions. The international guidelines
underline that single ALT and HBV DNA levels are insufficient
to assign the phase of infection or hepatitis. Hence, a
longitudinal follow-up with multiple measurements is required.
Hepatitis B core-related antigen (HBcrAg) is a novel serological
marker with promising clinical value but an evaluation on a
large European cohort has yet to be performed. Methods:
Multicenter study including 1584 samples from individuals in
HBeAg negative phase from 9 centers. HBV DNA, HBsAg,
HBcrAg and ALT were collected. The patients are categorized
in three groups according to EASL guidelines as chronic
hepatitis B (CHB, N=552), chronic infection B (CI-B, N=720),
chronic infection with fluctuating low viremia (CI-low viremia,
HBV DNA<20,000IU/mL, N=322). Data were collected
anonymized through a protected eCloud sharefile and
analyzed with software R v3.4.3 by an independent statistician
(IDDI). The concentration of HBcrAg is expressed in arbitrary
unit (Fujirebio, Lumipulse G HBcrAg, RUO). Results: Patients
were primarily male (59%) and Caucasian (57%), mean age
44 (range 9-79). HBV genotypes were 15% A, 2% B, 2% C,
45% D, 9% E, 1% F and 26 % unknown. Mean values (SD)
for HBV DNA were 3.6 (1.80) logIU/mL, HBcrAg 3.3 (1.47)
logU/mL and HBsAg 3.2 (1.02) logIU/mL. The ROC-curve for
HBsAg had an area under the curve (AUC) of 0.73 (95%CI
[0.70, 0.76]), with optimal cut-off for HBsAg of 2.99 LogIU/
mL (95%CI [2.84, 3.44]), sensitivity of 0.52 and specificity of
0.88, respectively. The ROC-curve for HBcrAg had an AUC of
0.97 (95%CI [0.96, 0.98]), suggesting a high diagnostic value
to discriminate between CHB and CI-B regardless of HBV
genotype. The optimal cut-off for HBcrAg was 3.14 LogU/
mL (95% CI [3.02, 3.27]), sensitivity of 0.93, specificity of
0.92, NPV of 0.91 and PPV of 0.94, respectively. Combining
HBcrAg and HBsAg did not further improve the diagnostic
performance of HBcrAg only. Classification of CI-low viremia
patients according to the HBcrAg cut-off was 19 % CHB and
81% CI-B. Conclusion: Along with HBV DNA and ALT, serum
HBcrAg may be a useful biomarker for a faster identification
of inactive chronic HBV-infection from CHB, independently
of HBV genotype. Combination with serum HBsAg did not
improve its diagnostic performance.

StephenW

2077
乙型肝炎核心相关抗原是更好的
标记比HBsAg之间的区别
慢性HBV感染和慢性乙型肝炎
在一个HBeAg阴性的欧洲队列中。
Maurizia R. Brunetto1，Ivana Carey2，Benjamin Maasoumy3，
Cristina Marcos4，Gijs Van Halewijn5，Gian Paolo Caviglia6，
Alessandro Loglio7，Daniela Cavallone8，Caroline Scholtes9，
Antonina Smedile10，Mar Riveiro-Barciela11，Florian van
Bömmel12，Annemiek Van Der Eijk13，Fabien Zoulim9，
Thomas Berg14，Markus Cornberg15，Pietro Lampertico16，
Kosh Agarwal17和Maria Buti18，（1）Hepatology Unit
和分子遗传学与病理学实验室
意大利比萨大学肝炎病毒，（2）
国王学院医院肝脏研究所（3）
胃肠病学，肝脏病学和内分泌学，汉诺威
德国汉诺威医学院，（4）医院肝脏科
瓦尔德希伯伦大学，西班牙巴塞罗那，（5）系
病毒科学，伊拉斯谟MC大学医学中心，（6）
都灵大学医学系，都灵，
意大利，（7）胃肠病学和肝病学，
FondazioneIrccsCàGrandaOspedale Maggiore Policlinico，
UniversitàDegliStudi Di Milano，意大利，（8）Hepatology Unit，
比萨大学医院，（9）肝病科，
Croix Rousse医院，Hospices Civils De Lyon，法国，
（10）都灵大学医学系，
意大利，（11）Vall D'hebron大学医院肝脏科，
西班牙巴塞罗那，（12）美国巴塞罗那市肝病科
大学医院消化内科和风湿病学
莱比锡，德国，（13）伊拉斯谟病毒科学系
荷兰鹿特丹MC大学医学中心，（14）
消化内科和风湿病科
莱比锡大学医院肝病学系，（15）
胃肠病学，肝脏病学和内分泌学，
汉诺威医学院，德国汉诺威，（16）分部
消化内科和肝脏病学，Fondazione Irccs Ca'
Granda Ospedale Maggiore Policlinico，UniversitàDegliStudi
Di Milano，米兰，意大利，（17）肝脏研究所，King's
大学医院NHS信托，（18）肝脏单位，Vall D'Hebron
西班牙巴塞罗那大学医院
背景：慢性乙型肝炎的自然史
感染的特征在于宿主病毒的多个阶段
相互作用和阶段的知识是必要的
做出治疗决定。国际准则
强调单个ALT和HBV DNA水平不足
分配感染或肝炎的阶段。因此，a
需要进行多次测量的纵向随访。
乙型肝炎核心相关抗原（HBcrAg）是一种新型血清学
具有良好临床价值的标志物，但对a
欧洲大型队列尚未开展。方法：
多中心研究，包括来自个体的1584个样本
来自9个中心的HBeAg阴性期。 HBV DNA，HBsAg，
收集HBcrAg和ALT。患者被分类
根据EASL指南分为三组，为慢性
乙型肝炎（CHB，N = 552），慢性感染B（CI-B，N = 720），
慢性感染伴低波动的低血症（CI低病毒血症，
HBV DNA <20,000IU / mL，N = 322）。收集数据
通过受保护的eCloud共享文件进行匿名处理
由独立的统计学家用软件R v3.4.3进行分析
（IDDI）。 HBcrAg的浓度任意表示
单位（Fujirebio，Lumipulse G HBcrAg，RUO）。结果：患者
主要是男性（59％）和高加索人（57％），平均年龄
44（范围9-79）。 HBV基因型为15％A，2％B，2％C，
45％D，9％E，1％F和26％未知。平均值（SD）
HBV DNA为3.6（1.80）logIU / mL，HBcrAg 3.3（1.47）
logU / mL和HBsAg 3.2（1.02）logIU / mL。 ROC曲线
HBsAg的曲线下面积（AUC）为0.73（95％CI
[0.70,0.76]），HBsAg的最佳截止值为2.99 LogIU /
mL（95％CI [2.84,3.44]），灵敏度0.52和特异性
分别为0.88。 HBcrAg的ROC曲线的AUC为
0.97（95％CI [0.96,0.98]），表明诊断价值高
无论HBV如何，都要区分CHB和CI-B
基因型。 HBcrAg的最佳截止值为3.14 LogU /
mL（95％CI [3.02,3.27]），灵敏度0.93，特异性
0.92，NPV为0.91，PPV为0.94。结合
HBcrAg和HBsAg没有进一步改善诊断
仅HBcrAg的表现。 CI低病毒血症的分类
根据HBcrAg临界值的患者为19％CHB和
81％CI-B。结论：HBV DNA和ALT，血清
HBcrAg可能是更快识别的有用生物标志物
CHB无活动的慢性HBV感染，独立
HBV基因型与血清HBsAg组合没有
提高其诊断性能。