慢性乙型肝炎患者在不同疾病阶段和抗病毒治疗下的HBV RNA谱

StephenW

HBV RNA profiles in chronic hepatitis B patients under different disease phases and anti‐viral therapy
Lung‐Yi Mak
Gavin Cloherty
Danny Ka‐Ho Wong
Jeffrey Gersch
Wai‐Kay Seto
James Fung
Man‐Fung Yuen
First published: 06 November 2020
https://doi.org/10.1002/hep.31616

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.1002/hep.31616
PDFPDF
Tools
Share
Abstract
Background and Aims

Large‐scale comprehensive studies on hepatitis B virus (HBV) RNA in chronic hepatitis B are lacking. We aimed to study HBV RNA profile and its correlation with other viral markers in CHB treatment‐naïve patients and patients receiving nucleos(t)ide analogues (NA).
Approach & Results

Novel biomarkers including HBV RNA and hepatitis B core‐related antigen (HBcrAg) were measured in 388 patients. Of these, 246 were treatment‐naïve and were categorized into HBeAg‐positive chronic infection (n=41), HBeAg‐positive chronic hepatitis (n=81), HBeAg‐negative chronic infection (n=39), HBeAg‐negative chronic hepatitis (n=66), and HBsAg seroclearance (n=19). These biomarkers were also measured in 142 NA‐treated patients receiving tenofovir or entecavir at baseline, week 48 and 96. The pattern of serum HBV RNA levels mirrored HBV DNA (1‐2 logs higher than HBV RNA) and HBcrAg in treatment‐naïve patients. HBV RNA correlated best with HBcrAg (r=0.84), and to a lesser extent with HBV DNA (r=0.737) (both p<0.001). In patients with HBsAg seroclearance, 15.8% and 15.8% had detectable serum HBV RNA and HBcrAg, respectively. NA treatment reduced serum HBV RNA by 1.46 logs and 1.77 logs at week 48 and week 96, respectively. At week 96 of NA therapy, only 19.1% tenofovir‐treated and 25.7% entecavir‐treated patients had unquantifiable HBV RNA (p>0.05). In treated‐patients with undetectable HBV DNA, 77.5% and 30% had quantifiable HBV RNA and HBcrAg respectively.
Conclusions

HBV RNA showed distinct and corresponding profile in HBV patients in different disease phases. HBV RNA and HBcrAg could be used to monitor residual transcriptional activities in patients with HBsAg seroclearance. NA led to reduction of serum HBV RNA. Monitoring of viral activities can still be achieved in patients with undetectable HBV DNA by serum HBV RNA.

StephenW

慢性乙型肝炎患者在不同疾病阶段和抗病毒治疗下的HBV RNA谱
麦龙Y
加文·克洛蒂（Gavin Cloherty）
黄家豪
杰弗里·格施（Jeffrey Gersch）
威凯濑户
冯国荣
袁文凤
首次发布：2020年11月6日
https://doi.org/10.1002/hep.31616

本文已被接受发表，并且经过了完整的同行评审，但尚未经过复制编辑，排版，分页和校对过程，因此可能会导致此版本与“记录版本”之间的差异。请引用本文作为doi：10.1002 / hep.31616
PDF格式
工具类
分享
抽象
背景和目标

缺乏关于慢性乙型肝炎的乙型肝炎病毒（HBV）RNA的大规模综合研究。我们旨在研究未接受过CHB治疗的患者和接受核苷酸（t）核苷酸类似物（NA）的患者的HBV RNA谱及其与其他病毒标记的相关性。
方法与结果

在388例患者中测量了包括HBV RNA和乙型肝炎核心相关抗原（HBcrAg）在内的新型生物标志物。其中，有246例未经治疗，分为HBeAg阳性慢性感染（n = 41），HBeAg阳性慢性肝炎（n = 81），HBeAg阴性慢性感染（n = 39），HBeAg阴性慢性肝炎（n = 66）和HBsAg血清清除率（n = 19）。在第48周和第96周的基线时，在接受NA替诺福韦或恩替卡韦治疗的142例接受NA治疗的患者中也测量了这些生物标志物。未经治疗的患者的血清HBV RNA水平反映了HBV DNA（比HBV RNA高1-2个对数）和HBcrAg 。 HBV RNA与HBcrAg的相关性最佳（r = 0.84），与HBV DNA的相关性较小（r = 0.737）（均p <0.001）。在HBsAg血清清除的患者中，血清HBV RNA和HBcrAg分别可检测到15.8％和15.8％。 NA治疗在第48周和第96周时分别使血清HBV RNA降低了1.46 log和1.77 log。在NA治疗第96周时，只有19.1％替诺福韦治疗和25.7％恩替卡韦治疗的患者存在无法量化的HBV RNA（p> 0.05）。在检测不到HBV DNA的接受治疗的患者中，分别有77.5％和30％的HBV RNA和HBcrAg可量化。
结论

HBV RNA在不同疾病阶段的HBV患者中表现出不同且相对应的特征。 HBV RNA和HBcrAg可用于监测HBsAg血清清除患者的残余转录活性。 NA导致血清HBV RNA降低。通过血清HBV RNA仍无法检测到HBV DNA的患者仍可以监测病毒活性。