从头开始乙型肝炎e抗原阴性慢性乙型肝炎患者血清乙型肝炎

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从头开始乙型肝炎e抗原阴性慢性乙型肝炎患者血清乙型肝炎病毒RNA的检测、组成及临床意义

    Andreas Laras、Margarita Papatheodoridi、Eleni Panopoulou、George V. Papatheodoridis、Stephanos J. Hadziyannis 和 Emilia Hadziyannis

病毒学杂志第 19 卷，文章编号：22 (2022) 引用这篇文章

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抽象的
背景

血清乙型肝炎病毒 (HBV) RNA 是肝内共价闭合环状 DNA (cccDNA) 转录活性和持久性的替代生物标志物。在这项回顾性研究中，我们调查了它在从头算乙型肝炎 e 抗原 (HBeAg) 阴性慢性感染患者中的存在、水平和组成，并检查了与疾病活动和核苷（酸）类似物（NA）停药结果的可能关联。
方法

我们开发了一种灵敏的实时聚合酶链式反应 (RT-PCR)，用于特异性检测 HBV 前基因组 RNA (pgRNA) 和前核心 (preC) mRNA，并分析了 116 名最初对 HBeAg 呈阴性的希腊患者的 220 份血清样本，其中 160 份接受 NA 治疗.
结果

在 31% 的样本中检测到 HBV pgRNA，在 15% 的样本中检测到 preC mRNA，其水平较低，代表总核心启动子的一小部分 (3.4%) 产生了转录物。在没有 NAs 的情况下，57% 的样本中检测到 pgRNA，中值为 5.19 (2.61–8.35) log10 cp/mL，低于 HBV DNA，并且与 ALT (r = 0.764) 和血清 HBV DNA 显着相关（ r = 0.906）。观察到大范围的 HBV DNA/pgRNA 比率，患者间和患者间存在显着差异。在 NA 治疗期间，pgRNA 表现出低可检测性 (22%) 和可变水平，中位数为 3.97 (2.30–8.13) log10 cp/mL，并且与治疗持续时间呈显着负相关 (r = − 0.346, p < 0.01 ）。在 74 例 NA 停用事件中，治疗结束时 pgRNA 阳性与 pgRNA 阴性病例相比，病毒学 (p = 0.016) 和临床 (p = 0.011) 复发的频率更高。
结论

在基因型 D 从头算 HBeAg 阴性患者中，血清 HBV RNA 主要由 pgRNA 加上一小部分 preC mRNA 转录物组成。血清 pgRNA 与疾病活动相关，表明感染肝细胞的裂解可能是未治疗患者和 NA 治疗早期血清 HBV RNA 的来源。在长期 NA 治疗期间，可检测到的血清 pgRNA 可预测治疗中断后的病毒反弹和临床复发，因此可作为决定停止治疗的标志物。

StephenW

Serum hepatitis B virus RNA detectability, composition and clinical significance in patients with ab initio hepatitis B e antigen negative chronic hepatitis B

    Andreas Laras, Margarita Papatheodoridi, Eleni Panopoulou, George V. Papatheodoridis, Stephanos J. Hadziyannis & Emilia Hadziyannis

Virology Journal volume 19, Article number: 22 (2022) Cite this article

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Abstract
Background

Serum hepatitis B virus (HBV) RNA is a surrogate biomarker for intrahepatic covalently closed circular DNA (cccDNA) transcriptional activity and persistence. In this retrospective study, we investigated its presence, levels and composition in ab initio Hepatitis B e antigen (HBeAg) negative chronically infected patients and examined possible associations with disease activity and the outcome of nucleos(t)ide analogue (NA) discontinuation.
Methods

We developed a sensitive real time polymerase chain reaction (RT-PCR) for the specific detection of HBV pregenomic RNA (pgRNA) and precore (preC) mRNA and analyzed 220 serum specimens, 160 under NA treatment, from 116 Greek patients initially negative for HBeAg.
Results

HBV pgRNA was detected in 31% and preC mRNA in 15% of samples, at lower levels representing a small fraction (3.4%) of total core promoter produced transcripts. In the absence of NAs, pgRNA was detected in 57% of samples with median value of 5.19 (2.61–8.35) log10 cp/mL, at lower levels than HBV DNA and correlated significantly with ALT (r = 0.764) and serum HBV DNA (r = 0.906). A wide range of HBV DNA/pgRNA ratio was observed with significant inter- and intra-patient variation. During NA treatment, pgRNA displayed low detectability (22%) and variable levels, median 3.97 (2.30– 8.13) log10 cp/mL, as well as, a significant inverse correlation with the duration of treatment (r = − 0.346, p < 0.01). In 74 events of NA discontinuation, end-of-treatment pgRNA-positive compared to pgRNA-negative cases, experienced more frequently virological (p = 0.016) and clinical (p = 0.011) relapse.
Conclusions

In genotype D ab initio HBeAg negative patients, serum HBV RNA is primarily composed of pgRNA plus a minor fraction of preC mRNA transcripts. Serum pgRNA is associated with disease activity, suggesting lysis of infected hepatocytes as a possible source of serum HBV RNA in untreated patients and in the early phase of NA treatment. During long term NA treatment, detectable serum pgRNA predicts viral rebound and clinical relapse following treatment discontinuation and may thus serve as a marker for the decision of cessation of therapy.

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https://virologyj.biomedcentral. ... /s12985-022-01749-7