致编辑的信：使用前基因组HBV RNA和HBcrAg预测乙型肝炎病毒感

StephenW

Letter to the Editor: Use of Pre-genomic HBV RNA and HBcrAg to Predict Cure of Hepatitis B Virus Infection
Henry Lik-Yuen Chan  1
Affiliations
Affiliation

    1
    Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.

    PMID: 32687649 DOI: 10.1002/hep.31469

Abstract

I read with great interest the article by Carey and colleagues on the dynamics of pregenomic hepatitis B virus (HBV) RNA and hepatitis B core related antigen (HBcrAg) among patients on nucleos(t)ide analogue (NA) therapy(1). Both HBcrAg and HBV RNA are products of transcriptional activities of covalently closed circular DNA (cccDNA). Although HBcrAg is a test for 3 HBV proteins, it measures primarily hepatitis B core antigen in hepatitis B e antigen (HBeAg)-negative patients. Carey and colleagues reported that patients who developed severe flare after stopping NA tend to have detectable and higher HBV RNA and HBcrAg levels than those who have milder flares.

Keywords: HBsAg; entecavir; functional cure; hepatitis flare; tenofovir.

This article is protected by copyright. All rights reserved.

StephenW

致编辑的信：使用前基因组HBV RNA和HBcrAg预测乙型肝炎病毒感染的治愈
陈力源1
隶属关系
联系

    1个
    香港中文大学医学与治疗学系，香港。

    PMID：32687649 DOI：10.1002 / hep.31469

抽象

我非常感兴趣地阅读了Carey及其同事关于在核苷酸（t）ide类似物（NA）治疗中患者中的基因组前乙型肝炎病毒（HBV）RNA和乙型肝炎核心相关抗原（HBcrAg）动态的文章（1）。 HBcrAg和HBV RNA都是共价闭合环状DNA（cccDNA）转录活性的产物。尽管HBcrAg可以检测3种HBV蛋白，但它主要测量的是乙肝e抗原（HBeAg）阴性患者的乙肝核心抗原。 Carey及其同事报告说，停止NA后出现严重耀斑的患者比那些患有轻微耀斑的患者往往具有可检测到的更高的HBV RNA和HBcrAg水平。

关键字：HBsAg；恩替卡韦功能性治疗；肝炎替诺福韦。

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StephenW

To the editor:I read with great interest the article by Carey and colleagues on the dynamics of pregenomic hepatitis B virus (HBV) RNA and hepatitis B core related antigen (HBcrAg) among patients on nucleos(t)ide analogue (NA) therapy(1). Both HBcrAg and HBV RNA are products of transcriptional activities of covalently closed circular DNA (cccDNA). Although HBcrAg is a test for 3 HBV proteins, it measures primarily hepatitis B core antigen in hepatitis B e antigen (HBeAg)-negative patients. Carey and colleagues reported that patients who developed severe flare after stopping NA tend to have detectable and higher HBV RNA and HBcrAg levels than those who have milder flares. This observation is very logical as patients who have active transcriptional activities of cccDNA are more likely having flares once NA is stopped. The more interesting finding is failure of HBcrAg and HBV RNA to predict mild flares after stopping NA. One possibility is lack of sensitivity of the tests. Even at baseline when HBV DNA was high, 29% patients had undetectable HBcrAg and 17% patients had undetectable HBV RNA. However, another possibility is the inadequacy of cccDNA activity to predict a cure. Most patients who stopped NA in Cohort B had relatively high hepatitis B surface antigen (HBsAg) level (median 3.41 log IU/ml). Previous reports, mostly from Asia, suggested that HBsAg at <100 IU/ml could best predict inactive disease after stopped NA in HBeAg-negative patients(2). As HBsAg is measuring activities from both integrated HBV DNA and cccDNA, a low HBsAg in NA-treated patients should indicate host immune clearance of HBV(3). With the current findings, will the authors recommend a strategy to stop NA based on HBcrAg, HBV RNA, and/or HBsAg? The authors also mentioned the possible use of these viral markers in future newer therapies against HBV. As HBcrAg and HBV RNA might be targets of future therapy, for example capsid assembly inhibitor or RNA interference, the meaning of these viral markers may be similar to that of HBV DNA in NA treatment(4). It will be interesting to know the insight from this paper into the use to these markers for HBV cure.

StephenW

致编者：我非常感兴趣地阅读了Carey及其同事关于接受核苷酸（t）ide类似物（NA）治疗的患者中基因组前乙型肝炎病毒（HBV）RNA和乙型肝炎核心相关抗原（HBcrAg）动态的文章（ 1）。 HBcrAg和HBV RNA都是共价闭合环状DNA（cccDNA）转录活性的产物。尽管HBcrAg可以检测3种HBV蛋白，但它主要测量的是乙肝e抗原（HBeAg）阴性患者的乙肝核心抗原。 Carey及其同事报告说，停止NA后出现严重耀斑的患者比那些患有轻微耀斑的患者往往具有可检测到的更高的HBV RNA和HBcrAg水平。这种观察是非常合乎逻辑的，因为一旦NA停止，具有cccDNA主动转录活性的患者更有可能出现耀斑。更有趣的发现是在停止NA后HBcrAg和HBV RNA无法预测轻度发作。一种可能性是缺乏测试的敏感性。即使在基线时HBV DNA高，也有29％的患者检测不到HBcrAg，17％的患者检测不到HBV RNA。但是，另一种可能性是cccDNA活性不足以预测治愈。在队列B中停止NA的大多数患者的乙肝表面抗原（HBsAg）水平相对较高（中位数为3.41 log IU / ml）。先前的报道（主要来自亚洲）表明，HBeAg阴性患者停用NA后，<100 IU / ml的HBsAg可以最好地预测失活疾病（2）。由于HBsAg可以测量整合的HBV DNA和cccDNA的活性，因此NA治疗的患者中HBsAg较低应表明宿主对HBV的免疫清除率（3）。根据目前的发现，作者是否会建议一种基于HBcrAg，HBV RNA和/或HBsAg停止NA的策略？作者还提到了这些病毒标记物可能会在未来针对HBV的新疗法中使用。由于HBcrAg和HBV RNA可能是未来治疗的目标，例如衣壳装配抑制剂或RNA干扰，因此这些病毒标记的含义可能与NA治疗中的HBV DNA相似（4）。了解本文对这些标志物在HBV治愈中的应用的见解将是很有趣的。