抗病毒治疗可降低HBsAg的比较生物标志物显示定量HBsAg（qHBsAg

StephenW

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg)
Seng Gee Lim  1   2 , Wah Wah Phyo  1 , Joanna Zhi Jie Ling  3 , Gavin Cloherty  4 , Emily K Butler  4 , Mary C Kuhns  4 , Anne L McNamara  4 , Vera Holzmayer  4 , Jeffrey Gersch  4 , Wei Lyn Yang  5 , Jing Hieng Ngu  6 , Jason Chang  6 , Jessica Tan  7 , Taufique Ahmed  8 , Yock Young Dan  1   2 , Yin Mei Lee  1   2 , Guan Huei Lee  1   2 , Poh Seng Tan  1 , Daniel Q Huang  1   2 , Htet Toe Wai Khine  1 , Chris Lee  1 , Amy Tay  1 , Edwin Chan  3
Affiliations
Affiliations

    1
    Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore.
    2
    Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
    3
    Singapore Clinical Research Institute, Singapore.
    4
    Abbott Laboratories, Abbott Park, IL, USA.
    5
    Tan Tock Seng Hospital, Singapore.
    6
    Singapore General Hospital, Singapore.
    7
    Changi General Hospital, Singapore.
    8
    Khoo Teck Puat Hospital, Singapore.

    PMID: 33159496 DOI: 10.1111/apt.16149

Abstract

Background: Biomarkers such as quantitative HBsAg (qHBsAg), quantitative hepatitis B virus (HBV) core-related antigen (qHBcrAg) and HBV RNA may be useful in predicting HBsAg loss in patients with chronic hepatitis B (CHB) undergoing antiviral therapy.

Aim(s): Our study evaluated qHBsAg, HBV RNA and qHBcrAg as a posthoc analysis of a randomized clinical trial of peginterferon±NA to determine their utility in predicting HBsAg loss.

Methods: CHB patients who completed therapy with 48weeks peginterferon alpha2b ± nucleoside analogue therapy (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBsAg loss. The predictive ability of qHBsAg, qHBcrAg, HBV RNA and other variables were investigated by univariate and multivariate logistic models for HBeAg-negative patients by odds ratios, area under the curve (AUC), sensitivity, specificity, and positive and negative likelihood ratios (LR).

Results: HBsAg loss occurred in 15/114(13%) HBeAg-negative CHB patients who completed 48 weeks of peginterferon. At baseline, qHBsAg was superior to HBcrAg and HBV RNA with AUC 0.916, 0.649 and 0.542, respectively. Using multivariate analysis, the model comprising treatmentarm, age, gender, baseline qHBsAg, HBcrAg and HBV RNA, weeks 4 & 8 qHBsAg had the highest AUC(0.98), but the univariate model with week 8 qHBsAg <70 IU/mL had AUC 0.96. Hence, the contributions of variables other than qHBsAg were marginal. HBV RNA and qHBcrAg were weak predictors of HBsAg loss. Kinetics of the novel markers showed only qHBsAg had a good relationship with HBsAg loss while HBV RNA had a marginal relationship and HBcrAg did not change at all, and none had a good relationship with viral rebound.

Conclusions: On-treatment biomarker predictors were better than baseline ones, and the best predictor of HBsAg loss at 72 weeks was week 8 qHBsAg <70 IU/mL.

© 2020 John Wiley & Sons Ltd.

StephenW

抗病毒治疗可降低HBsAg的比较生物标志物显示定量HBsAg（qHBsAg）的主要影响
Seng Gee Lim 1 2，Wah Wah Phyo 1，Joanna Zhi Jie Ling 3，Gavin Cloherty 4，Emily K Butler 4，Mary C Kuhns 4，Anne L McNamara 4，Vera Holzmayer 4，Jeffrey Gersch 4，Wei Lyn Yang 5，静邱恩古6，张杰森6，杰西卡·坦7，陶菲克·艾哈迈德8，霍克·丹丹1 2，尹美莉1 2，关惠李1 2，宝盛丹1，丹尼尔·黄1 2，喜剧趾围Khine 1 ，克里斯·李1，艾米·泰1，陈冠希3
隶属关系
隶属关系

    1个
    新加坡国立大学卫生系统医学部消化内科和肝病科。
    2
    新加坡国立大学Yong Loo Lin医学院，新加坡。
    3
    新加坡新加坡临床研究所。
    4
    美国伊利诺伊州雅培公园的雅培实验室。
    5
    新加坡陈笃生医院。
    6
    新加坡新加坡总医院。
    7
    新加坡樟宜综合医院。
    8
    新加坡Khoo Teck Puat医院。

    PMID：33159496 DOI：10.1111 / apt.16149

抽象

背景：定量HBsAg（qHBsAg），定量乙型肝炎病毒（HBV）核心相关抗原（qHBcrAg）和HBV RNA等生物标志物可用于预测接受抗病毒治疗的慢性乙型肝炎（CHB）患者的HBsAg丢失。

目的：我们的研究评估了qHBsAg，HBV RNA和qHBcrAg作为peginterferon±NA随机临床试验的事后分析，以确定它们在预测HBsAg损失中的效用。

方法：在第72周评估完成48周peginterferon alpha2b±核苷类似疗法（clinicaltrial.gov NCT01928511）治疗的CHB患者的HBsAg丢失。通过单因素和多因素对数模型对HBeAg阴性患者的qHBsAg，qHBcrAg，HBV RNA和其他变量的预测能力，通过比值比，曲线下面积（AUC），敏感性，特异性以及正负似然比（LR）进行调查）。

结果：完成peginterferon治疗48周的HBeAg阴性CHB患者中有15/114（13％）发生了HBsAg丢失。基线时，qHBsAg优于HBcrAg和HBV RNA，AUC分别为0.916、0.649和0.542。使用多变量分析，该模型包括治疗组，年龄，性别，基线qHBsAg，HBcrAg和HBV RNA，第4周和第8周qHBsAg的AUC最高（0.98），而第8周qHBsAg <70 IU / mL的单变量模型的AUC 0.96 。因此，除qHBsAg以外的变量的贡献很小。 HBV RNA和qHBcrAg是HBsAg丢失的弱预测指标。新标记的动力学表明，仅qHBsAg与HBsAg丢失有良好的关系，而HBV RNA则具有边际关系，而HBcrAg完全没有变化，并且与病毒反弹均无良好关系。

结论：治疗中生物标志物的预测指标优于基线指标，并且在72周时HBsAg丧失的最佳预测指标是第8周qHBsAg <70 IU / mL。

分级为4 +©2020 John Wiley＆Sons Ltd.