核苷（酸）类似物治疗或未治疗的患者在慢性和急性感染期

StephenW

HBV serum DNA and RNA levels in nucleos(t)ide analogue‐treated or untreated patients during chronic and acute infection
Emily K. Butler PhD
Jeffrey Gersch
Anne McNamara
Ka‐Cheung Luk PhD
Vera Holzmayer
Maria de Medina
Eugene Schiff MD
Mary Kuhns PhD
Gavin A. Cloherty PhD
https://doi.org/10.1002/hep.30082

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ABSTRACT

Treatment of chronic hepatitis B (CHB) patients with nucleos(t)ide analogues (NA) suppresses HBV DNA synthesis but does not affect synthesis of HBV pregenomic RNA (pgRNA). HBV pgRNA is detectable in the serum during NA treatment and has been proposed as a marker of HBV covalently closed circular DNA (cccDNA) activity within the infected hepatocyte. We developed an automated assay for the quantification of serum HBV pgRNA using a dual‐target qRT‐PCR approach on the Abbott m2000sp/rt system. We demonstrate accurate detection and quantification of serum HBV RNA. HBV DNA was quantified using the Abbott RealTime HBV viral load assay. We further compared serum nucleic acid levels and kinetics in HBV‐positive populations. Samples included: on‐therapy CHB samples (N=16), samples (N=89) from 10 treatment naïve CHB subjects receiving 12‐weeks of NA treatment with 8‐week follow‐up, HBsAg‐positive blood donor samples (N=102), and 3 seroconversion series from plasmapheresis donors (N=79 samples).

Conclusion: During NA treatment of CHB subjects, we observed low correlation of HBV DNA to pgRNA levels; pgRNA concentration was generally higher than HBV DNA concentrations. In contrast, when NA treatment was absent we observed serum pgRNA at concentrations that correlated to HBV DNA and were approximately 2 log lower than HBV DNA. Importantly, we observe this trend in untreated subject samples from both chronic infections and throughout seroconversion during acute infection. Results demonstrate that the presence of pgRNA in serum is part of the HBV lifecycle; constant relative detection of pgRNA and HBV DNA in the serum is suggestive of a linked mechanism for egress for HBV DNA or pgRNA containing virions. This article is protected by copyright. All rights reserved.

StephenW

核苷（酸）类似物治疗或未治疗的患者在慢性和急性感染期间的HBV血清DNA和RNA水平
Emily K. Butler博士
杰弗里格什
安妮麦克纳马拉
Ka-Cheung Luk博士
维拉霍尔兹迈耶
玛丽亚德梅迪纳
Eugene Schiff博士
Mary Kuhns博士
Gavin A. Cloherty博士
https://doi.org/10.1002/hep.30082

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用核苷类似物（NA）治疗慢性乙型肝炎（CHB）患者可抑制HBV DNA合成，但不影响HBV前基因组RNA（pgRNA）的合成。 HBV pgRNA在NA治疗期间可在血清中检测到，并且已被提议作为HBV感染肝细胞内HBV共价闭合环状DNA（cccDNA）活性的标志物。我们在Abbott m2000sp / rt系统上开发了一种使用双靶qRT-PCR方法定量血清HBV pgRNA的自动化分析。我们证明了血清HBV RNA的准确检测和定量。使用Abbott RealTime HBV病毒载量测定法定量HBV DNA。我们进一步比较了HBV阳性人群中的血清核酸水平和动力学。样本包括：来自10位未接受治疗的CHB受试者的治疗CHB样本（N = 16），样本（N = 89），接受12周的NA治疗，随访8周，HBsAg阳性献血者样本（N = 102）和3个来自血浆置换供体的血清转化系列（N = 79个样品）。

结论：慢性乙型肝炎患者NA治疗期间，我们观察到HBV DNA与pgRNA水平的低相关性; pgRNA浓度一般高于HBV DNA浓度。相反，当NA治疗不存在时，我们观察到与HBV DNA相关的浓度的血清pgRNA，比HBV DNA低大约2个对数值。重要的是，我们在急性感染期间来自慢性感染和整个血清转化的未治疗受试者样品中观察到这种趋势。结果表明血清中pgRNA的存在是HBV生命周期的一部分;对血清中pgRNA和HBV DNA的持续相对检测暗示了HBV DNA或含有pgRNA的病毒颗粒的出口的连接机制。本文受版权保护。版权所有。