EASL 2018 SAT-330 英国慢性乙型肝炎患者HBsAg清除的动态 感染

StephenW

EASL 2018 SAT-330
Dynamics of HBsAg clearance in a UK cohort of chronic HBV
infection
L. Downs1, M. Patel2, M.A. Ansari3, A. Mcnaughton3, M. Andersson1,
E. Barnes2,3, K. Jeffery1, P. Matthews1,3. 1Oxford University Hospitals
NHS Foundation Trust, Department of Infectious Diseases and
Microbiology, Oxford, United Kingdom; 2Oxford University Hospitals
NHS Foundation Trust, Department of Hepatology, Oxford, United
Kingdom; 3University of Oxford, Nuffield Department of Medicine,
Oxford, United Kingdom
Email: [email protected]
Background and Aims: Hepatitis B surface antigen (HBsAg) has
recently gained traction as a biomarker that may provide prognostic
information and inform treatment decisions in chronic hepatitis B
virus (HBV) infection. It may be particularly useful when HBV DNA
levels are lowand therefore difficult to quantify accurately, either as a
result of treatment or natural immune control of the virus. There are
fewpublished descriptions of the kinetics of HBV clearance, and most
existing data come from Asia. We therefore set out to identify adults
who cleared HBsAg in a UK cohort, to characterise those who clear,
and to describe the dynamics of HBsAg clearance.
Methods: Our cohort was collected from the records of a large UK
teaching hospital that provides >1 million patient contacts per year.
We measured serum HBsAg levels using the semi-quantitative Abbott
Architect i2000SR, and HBV DNA levels using the Cobas taqman assay
(Roche). We identified individuals with HBV infection confirmed
between 2011 and 2016 (n = 442), but in whom HBsAg levels fell
consistently (serial decline and two or more consecutive readings
<1000 IU/ml) or became completely undetectable.
Results: HBsAg clearance occurred in 21 of 442 individuals (4.8%),
and a further 43 (9.7%) progressed towards HBsAg clearance but did
not clear completely during the time period under review (total n =
64). In this group of 64, the median agewas 46 years (IQR 37–56), and
males predominated (39/64, 61%). The majoritywere HBeAg negative
(61/64, 95%) and had HBV DNA <20 IU/ml (42/64, 66%). The majority
of patients were treatment naïve (45/64, 70%). In individuals with an
elastography score recorded, most were <10 kPa (45/50, 90%). In this
clearance phase, there was no correlation between HBsAg and HBV
DNA viral load (p = 0.4). For individuals starting with HBsAg
≥1000 IU/ml, the median time to clearance was 46 months (IQR
29–58 months) (Figure). There was no difference in time to clearance
between patients on and off treatment (p = 0.6).
Conclusions: The majority of clearance events occurred in untreated
patients, suggesting an underlying immunological mechanism. In the
longer term, developing a robust understanding of the interplay
between host and virus that leads to HBsAg clearance could provide
insights into natural immunological control, and therefore underpin
newapproaches to immunotherapy. Developing insights into the use
of HBsAg as a biomarker could be influential in informing prognosis
and treatment of HBV, particularly in resource-limited settings in
which HBV DNA measurements are not accessible.

StephenW

EASL 2018 SAT-330
英国慢性乙型肝炎患者HBsAg清除的动态
感染
L. Downs1，M.Patel2，M.A.Assari3，A.Mcnaughton3，M.Andersson1，
E. Barnes2,3，K. Jeffery1，P. Matthews1,3。 10xford大学医院
NHS基金会信托基金，传染病和艾滋病司
微生物学，牛津，英国; 2Oxford大学医院
NHS基金会信托，美国牛津大学肝病学系
王国; 3牛津大学，纳菲尔德医学系，
牛津，英国
电子邮件地址：[email protected]
背景和目标：乙型肝炎表面抗原（HBsAg）有
最近获得了作为可提供预后的生物标志物的牵引力
信息并告知慢性乙型肝炎的治疗决定
病毒（HBV）感染。 HBV DNA可能特别有用
水平低，因此难以准确量化，无论是作为一个
治疗结果或病毒的天然免疫控制。有
关于HBV清除动力学的少数发表的描述，以及大多数
现有数据来自亚洲。因此，我们着手确定成年人
谁清除HBsAg在英国队列，描述谁清楚，
并描述HBsAg清除的动态。
方法：我们的队列是从一个大型英国的记录中收集的
每年提供> 100万患者接触的教学医院。
我们使用半定量Abbott测量血清HBsAg水平
建筑师i2000SR和使用Cobas taqman测定的HBV DNA水平
（Roche）的。我们确定了HBV感染确诊的个体
2011年至2016年（n = 442），但HBsAg水平下降
一致（连续下降和连续两次或更多的读数
<1000IU / ml）或完全检测不到。
结果：HBsAg清除发生在442人中的21人（4.8％），
另有43人（9.7％）进展为HBsAg清除，但确实如此
在审查的时间段内没有完全清除（总数n =
64）。在这组64人中，中位年龄为46岁（IQR 37-56），和
男性为主（39/64，61％）。多数为HBeAg阴性
（61 / 64,95％），HBV DNA <20IU / ml（42 / 64,66％）。大多数
的患者初次接受治疗（45/64，70％）。在与个人
记录弹性成像评分，大部分<10kPa（45 / 50,90％）。在这
清除阶段，HBsAg与HBV无相关性
DNA病毒载量（p = 0.4）。对于从HBsAg开始的个人
≥1000IU / ml，中位清除时间为46个月（IQR
29-58个月）（图）。清关时间没有区别
治疗期间和停止治疗之间（p = 0.6）。
结论：大部分清除事件发生在未经处理的情况下
提示了潜在的免疫学机制。在里面
从长远来看，对相互作用形成强有力的理解
导致HBsAg清除的宿主和病毒之间可能提供
洞察到自然免疫控制，因此是支撑
新的方法免疫疗法。开发使用见解
HBsAg作为生物标志物可能对预后有影响
和治疗HBV，尤其是在资源有限的环境中
哪些HBV DNA测量不可用。