AASLD2018[537]识别“真正的”功能性治疗的新标记 - HBsAg真的会

StephenW

537
A New Marker to Identify ‘True’ Functional Cure-
Is HBsAg Loss Truly HBsAg Loss?
Ivana Carey, Matthew Bruce, Bo Wang, Kathryn Oakes,
Geoffrey M. Dusheiko and Kosh Agarwal, Institute of Liver
Studies, King’s College Hospital
Background: Functional cure in chronic Hepatitis B (CHB)
is defined as a loss of HBsAg, non-detected HBV DNA and
absence of ongoing liver damage. Some patients achieve
HBsAg seroconversion – the presence of anti-HBsAg
antibodies (anti-HBs Ab) > 10 mIU/ml, but this is not a ‘gold
standard’ for ‘functional’ cure definition. Newer, more sensitive,
assays allow quantification of HBsAg to lower detection limits
and this may provide insight into resolution of infection in HBV.
Aim: To measure HBsAg levels using an ultrasensitive HBsAg
assay in CHB patients who achieved HBsAg loss and assess
whether there is any relationship between HBsAg and anti-
HBs Ab levels. Methods: Serum samples from 66 patients
(median age 45.7 years, 35 males) with history of HBsAg
positivity (median duration of total follow-up since diagnosis
7.5 years), and currently HBsAg negative by qualitative Abbott
ArchitectTM Assay (LOQ 0.01 IU/ml) with non-detected HBV
DNA (Cobas TaqMan; LOQ < 20 IU/ml) were collected. Levels
of HBsAg were measured by CLEIA Lumipulse HBsAg-HQ
(Fujirebio) (LOQ 0.5 mIU/ml). Concentrations of anti-HBs
Ab were determined by Abbott ArchitectTM (LOQ 0.1 mIU/
ml). HBsAg levels were stratified according to anti-HBs Ab
concentrations: 41 patients had anti-HBs Ab <10 mIU/ml vs.
25 patients with anti-HBsAg Ab ≥10 mIU/ml. Within this cohort,
23 patients had sequential plasma samples from the timepoint
of HBsAg negativity (median duration 1.5 year, range
0.9 – 5.2 years). Results: 62 out of 66 (94%) patients had
detected HBsAg by ultrasensitive HBsAg assay. All patients
(n=4) with non- detected ultrasensitive HBsAg had anti-HBs
Ab levels > 250 mIU/ml. Patients with low concentrations of
anti-HBs Ab (<10 mIU/ml) had higher ultrasensitive HBsAg
levels than patients with anti-HBs Ab ≥ 10 mIU/ml (median,
range HBsAg: 3.2 (0.8 – 77.9) vs. 0.6 (0-2.3) mIU/ml, p<0.01).
There was a strong inverse correlation between ultrasensitive
HBsAg levels and anti-HBs Ab concentrations (r=-0.61,
p<0.01). In 23 patients with sequential samples from anti-
HBs loss, the levels of ultrasensitive HBsAg were higher and
anti-HBs Ab concentrations were lower at the initial qualitative
HBsAg negativity time-point than in consecutive follow up
visit (median 1.5 year) (median HBsAg: 43 vs. 1.2 mIU/ml,
p<0.01; median anti-HBs Ab: 1.09 vs. 169 mIU/ml, p<0.01).
Conclusion: Ultrasensitive HBsAg assay may be a useful
tool to determine HBsAg levels in patients who achieve
HBsAg loss (by qualitative assay) and demonstrated dynamic
changes in conjunction with anti-HBs antibodies levels.
This marker may be an important adjunct in the context of
‘consolidation’ in HBV cure programs.

StephenW

537
识别“真正的”功能性治疗的新标记 -
HBsAg真的会丢失HBsAg吗？
Ivana Carey，Matthew Bruce，Bo Wang，Kathryn Oakes，
肝脏研究所的Geoffrey M. Dusheiko和Kosh Agarwal
研究，国王学院医院
背景：慢性乙型肝炎（CHB）的功能性治愈
定义为HBsAg丢失，未检出HBV DNA和
没有持续的肝损伤。
HBsAg血清学转换 - 抗-HBsAg的存在
抗体（抗-HBs Ab）> 10 mIU / ml，但这不是'金
标准'用于'功能'固化定义。更新，更敏感，
评估HBsAg的定量以降低检测限
这可能为解决HBV感染提供了解。
目的：使用超敏感HBsAg测量HBsAg水平
在HBB患者中进行HBsAg丢失和评估的分析
HBsAg与抗体之间是否存在任何关系
HBs Ab水平。方法：66例患者的血清样本
（中位年龄45.7岁，男性35例），有HBsAg史
积极性（自诊断以来总的随访时间中位数）
7。5年），目前HBsAg由定性雅培负面
ArchitectTM Assay（LOQ 0.01 IU / ml），未检测到HBV
收集DNA（Cobas TaqMan; LOQ <20IU / ml）。水平
通过CLEIA Lumipulse HBsAg-HQ测量HBsAg
（Fujirebio）（LOQ 0.5 mIU / ml）。抗HBs的浓度
Ab由Abbott ArchitectTM确定（LOQ 0.1 mIU /
ML）。根据抗HBs Ab对HBsAg水平进行分层
浓度：41例患者抗-HBs抗体<10 mIU / ml vs.
25例抗-HBsAg抗体≥10mIU/ ml。在这个队列中，
23名患者从时间点开始连续血浆样本
HBsAg阴性（中位数持续1。5年，范围
0.9 - 5.2年）。结果：66例患者中有62例（94％）患有
通过超灵敏HBsAg测定检测HBsAg。所有患者
（n = 4）具有未检测到的超灵敏HBsAg具有抗HBs
Ab水平> 250 mIU / ml。低浓度的患者
抗-HBs Ab（<10 mIU / ml）具有更高的超敏HBsAg
与抗-HBs抗体≥10mIU / ml的患者相比（中位数，
范围HBsAg：3.2（0.8-77.9）对0.6（0-2.3）mIU / ml，p <0.01）。
超敏感之间存在强烈的反相关
HBsAg水平和抗HBs抗体浓度（r = -0.61，
P <0.01）。在23例患者中，来自抗体的连续样本
HBs丢失，超敏感HBsAg水平升高
抗HBs Ab浓度在初始定性时较低
HBsAg消极时间点比连续随访时间要长
访视（中位数为1。5年）（HBsAg中位数：43对1.2 mIU / ml，
P <0.01;中位抗-HBs Ab：1.09对169 mIU / ml，p <0.01）。
结论：超灵敏HBsAg检测可能是有用的
确定患者HBsAg水平的工具
HBsAg丢失（通过定性分析）和示范动态
与抗HBs抗体水平相关的变化。
该标记可能是上下文中的重要附属物
HBV治愈计划中的“巩固”。