免疫生物标志物作为HBeAg阴性慢性乙型肝炎患者停用核苷（酸

StephenW

J Viral Hepat. 2019 Jan 31. doi: 10.1111/jvh.13068. [Epub ahead of print]
Immunological biomarkers as indicators for outcome after discontinuation of nucleos(t)ide analogue therapy in patients with HBeAg negative chronic hepatitis B.
Kranidioti H1,2, Manolakopoulos S2,3, Kontos G2, Breen MS1, Kourikou A2, Deutsch M2, Quesada-Del-Bosque ME1, Martinez-Nunez RT1, Naiyer MM1, Woelk CH1, Sanchez-Elsner T1, Hadziyannis E3, Papatheodoridis G3, Khakoo SI1.
Author information

1
    Department of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, United Kingdom.
2
    2nd Academic Department of Internal Medicine, Hippokration General Hospital of Athens, Greece.
3
    Academic Department of Gastroenterology, Laiko General Hospital of Athens, Greece.

Abstract

The optimal duration of treatment with nucleos(t)ide analogues (NAs) for patients with HBeAg-negative Chronic Hepatitis B (CHB) is unknown. The aim of this study was to identify an immune signature associated with off-treatment remission to NA therapy. We performed microarray analysis of PBMCs from six patients with chronic hepatitis B who stopped NA therapy (3 with off-treatment remission, 3 with relapse) and 5 patients with chronic HBV infection (previously termed "inactive carriers") served as controls. Results were validated using qRT-PCR on a second group of 21 individuals (17 patients who stopped treatment and 4 controls). PBMCs from 38 patients on long-term NA treatment were analysed for potential to stop treatment. Microarray analysis indicated that patients with off-treatment remission segregated as a distinct out-group. Twenty-one genes were selected for subsequent validation. Ten of these were expressed at significantly lower levels in the patients with off-treatment remission compared to the patients with relapse and predicted remission with AUC of 0.78-0.92. IFNγ, IL-8, FASLG and CCL4 were the most significant by logistic regression. Twelve (31.6%) of 38 patients on long-term NA therapy had expression levels of all these four genes below cut-off values, and hence were candidates for stopping treatment. Our data suggest that patients with HBeAg-negative CHB who remain in off-treatment remission 3 years after NA cessation have a distinct immune signature and that PBMC RNA levels of IFNγ, IL-8, FASLG and CCL4 may serve as potential biomarkers for stopping NA therapy. This article is protected by copyright. All rights reserved.

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

Chronic hepatitis B; Nucleos(t)ide Analogues; treatment discontinuation

PMID:
    30702196
DOI:
    10.1111/jvh.13068

StephenW

J病毒肝病。 2019年1月31日doi：10.1111 / jvh.13068。 [印刷前的电子版]
免疫生物标志物作为HBeAg阴性慢性乙型肝炎患者停用核苷（酸）类似物治疗后的结果指标。
Kranidioti H1,2，Manolakopoulos S2,3，Kontos G2，Breen MS1​​，Kourikou A2，Deutsch M2，Quesada-Del-Bosque ME1，Martinez-Nunez RT1，Naiyer MM1，Woelk CH1，Sanchez-Elsner T1，Hadziyannis E3，Papatheodoridis G3 ，Khakoo SI1。
作者信息

1
    英国南安普顿大学医学院临床与实验科学系。
2
    希腊雅典Hippokration综合医院第二内科学术部。
3
    希腊雅典莱科总医院消化内科学系。

抽象

HBeAg阴性慢性乙型肝炎（CHB）患者使用核苷（酸）类似物（NAs）治疗的最佳时间尚不清楚。本研究的目的是确定与NA治疗的治疗后缓解相关的免疫特征。我们对6名接受NA治疗的慢性乙型肝炎患者（3名治疗后缓解，3名复发）和5名慢性HBV感染患者（以前称为“非活动性携带者”）的PBMC进行了微阵列分析。使用qRT-PCR对第二组21个个体（17个停止治疗的患者和4个对照）进行验证。对来自长期NA治疗的38名患者的PBMC进行了分析，以确定是否有可能停止治疗。微阵列分析表明，治疗后缓解的患者作为一个独特的外群体分离。选择21个基因用于后续验证。与复发和预测缓解的患者相比，其中10例在治疗后缓解患者中以显着较低的水平表达，AUC为0.78-0.92。通过逻辑回归，IFNγ，IL-8，FASLG和CCL4是最显着的。长期NA治疗的38名患者中有12名（31.6％）具有低于临界值的所有这四种基因的表达水平，因此是停止治疗的候选者。我们的数据表明HBeAg阴性CHB患者在停止后3年仍处于治疗后缓解期，具有明显的免疫特征，IFNγ，IL-8，FASLG和CCL4的PBMC RNA水平可作为阻止NA的潜在生物标志物。治疗。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：

慢性乙型肝炎; Nucleos（t）ide类似物;治疗中止

结论：
    30702196
DOI：
    10.1111 / jvh.13068