使用HBsAg表位谱分析预测基因型A慢性乙型肝炎中的HBsAg清除率

StephenW

Liver Int. 2019 Aug 4. doi: 10.1111/liv.14207. [Epub ahead of print]
Predicting HBsAg clearance in genotype A chronic hepatitis B using HBsAg epitope profiling: a biomarker for functional cure.
Walsh R1, Hammond R1, Yuen L1, Deerain J1, O'Donnell T1, Leary T2, Cloherty G2, Gaggar A3, Kitrinos K3, Subramanian M3, Wong D4, Locarnini S1.
Author information

1
    Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Doherty Institute, Melbourne, Victoria, Australia.
2
    Abbott Laboratories, Chicago, Illinois, USA.
3
    Gilead Sciences, Foster City, California, USA.
4
    Department of Gastroenterology, St Vincent's Hospital, Fitzroy, Victoria, Australia.

Abstract
BACKGROUND AND AIM:

Functional cure is the major goal of CHB therapy though few biomarkers predict this outcome. HBsAg epitope occupancy can be influenced by therapeutic and immune pressure. The aim of this study was to map the HBsAg epitope profiles during long term nucleos(t)ide analogue therapy in patients with genotype A CHB, in the context of HBsAg loss/seroconversion.
METHODS:

We evaluated 25 genotype A CHB patients in the GS-US-174-0103 trial of HBeAg-positive CHB patients treated with tenofovir or adefovir for 4 years, 14 who achieved HBsAg loss whilst 11 had no change. We epitope mapped the major domains of HBsAg to identify those patients with HBsAg clearance profile (loss of binding at both loops 1 and 2 epitopes of the "a" determinant) versus non-clearance profile (no change in epitope recognition, or loss of epitope binding at one loop only), correlating this to on-treatment HBsAg responses. Complexed anti-HBs was also measured.
RESULTS:

Analysis of the HBsAg epitope profiles of the 25 patients at baseline identified no predictive correlation with HBsAg loss. In contrast, analysis at week 48 and end of study (week 192) or prior to HBsAg loss identified significant predictive associations between development of HBsAg clearance profiles and outcome of functional cure. The detection of a clearance profile also correlated with the development of an ALT flare and detection of anti-HBs complexed with HBsAg.
CONCLUSION:

The detection of HBsAg clearance profiles by epitope mapping represents a novel viral biomarker, reflecting an emerging anti-HBs selection pressure prior to functional cure. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.
KEYWORDS:

ALT flare; HBsAg epitope mapping; HBsAg loss; antiviral therapy; functional cure; genotype A infected patients

PMID:
    31379058
DOI:
    10.1111/liv.14207

StephenW

肝脏国际2019年8月4日doi：10.1111 / liv.14207。 [印刷前的电子版]
使用HBsAg表位谱分析预测基因型A慢性乙型肝炎中的HBsAg清除率：功能性治愈的生物标志物。
Walsh R1，Hammond R1，Yuen L1，Deerain J1，O'Donnell T1，Leary T2，Cloherty G2，Gaggar A3，Kitrinos K3，Subramanian M3，Wong D4，Locarnini S1。
作者信息

1
    澳大利亚维多利亚州墨尔本Doherty研究所维多利亚传染病参考实验室分子研究与开发部。
2
    Abbott Laboratories，芝加哥，伊利诺伊州，美国。
3
    吉利德科学，福斯特城，加利福尼亚州，美国。
4
    澳大利亚维多利亚州菲茨罗伊圣文森特医院消化内科。

抽象
背景和目的：

功能性治愈是CHB治疗的主要目标，尽管很少有生物标志物预测这种结果。 HBsAg表位占有率可受到治疗和免疫压力的影响。本研究的目的是在HBsAg丢失/血清转换的背景下，在基因型A CHB患者的长期核苷（酸）类似物治疗期间绘制HBsAg表位谱。
方法：

我们在用替诺福韦或阿德福韦治疗4年的HBeAg阳性CHB患者的GS-US-174-0103试验中评估了25个基因型A CHB患者，其中14例达到HBsAg损失而11例没有变化。我们的表位定位了HBsAg的主要结构域，以确定具有HBsAg清除谱的患者（“a”决定簇的第1和第2个表位的结合丧失）与非清除谱（表位识别无变化或表位缺失）仅在一个环上结合），将其与治疗中的HBsAg反应相关联。还测量了复合的抗HBs。
结果：

对基线时25名患者的HBsAg表位谱的分析发现，与HBsAg缺失没有预测相关性。相反，在第48周和研究结束时（第192周）或HBsAg丢失之前的分析发现HBsAg清除谱的发展与功能性治愈的结果之间存在显着的预测关联。间隙谱的检测也与ALT突发的发展和与HBsAg复合的抗HBs的检测相关。
结论：

通过表位作图检测HBsAg清除谱代表了一种新的病毒生物标志物，反映了功能性治愈前出现的抗HBs选择压力。本文受版权保护。版权所有。

本文受版权保护。版权所有。
关键词：

ALT耀斑; HBsAg表位作图; HBsAg丢失;抗病毒治疗;功能性治疗;基因型A感染的患者

结论：
    31379058
DOI：
    10.1111 / liv.14207