Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China; Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.
Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China.
J Clin Virol. 2018 Feb-Mar;99-100:71-78. doi: 10.1016/j.jcv.2017.12.016. Epub 2018 Jan 6.
Both serum hepatitis B virus (HBV) DNA and RNA can reflect intrahepatic covalently closed circular DNA (cccDNA) activity. However, correlations among viral markers haven't been fully explored.
Here we investigated the correlations between serum HBV RNA and other viral markers in acute hepatitis B patients and treatment-naïve chronic HBV-infected individuals.
The serum viral markers of 19 acute hepatitis B patients and 84 treatment-naïve chronic HBV-infected individuals at different infection stages were quantified. Correlations among viral markers were analyzed by Pearson's or Spearman's correlation analysis.
Serum viral markers and intrahepatic cccDNA levels were lower in acute hepatitis B patients than in treatment-naïve chronic HBV-infected individuals. Serum HBV RNA levels were positively correlated with serum HBV DNA, HBsAg and intrahepatic cccDNA levels in HBeAg-positive chronic HBV-infected individuals. Total serum HBV nucleic acids (HBV DNA plus RNA) showed superiority in reflecting intrahepatic cccDNA activity. Stratified analysis revealed that such correlations were only found in HBeAg-positive chronic hepatitis B phase. Moreover, high-frequency R193M and P196A mutations were found in the RT region of HBV polymerase leading to lower serum HBV DNA and higher serum HBV RNA levels in HBeAg-negative chronic HBV infection phase.
HBV replication capability was lower in acute hepatitis B patients than in chronic HBV-infected individuals. In treatment-naïve HBeAg-positive chronic HBV-infected individuals, serum HBV DNA plus RNA showed superiority in reflecting intrahepatic cccDNA activity than each alone. Moreover, mutated RT region of HBV polymerase might lead to the attenuated reverse transcriptional activity of HBV polymerase in HBeAg-negative chronic HBV infection phase.
血清乙型肝炎病毒 (HBV) DNA 和 RNA 均可反映肝内共价闭合环状 DNA (cccDNA) 的活性。然而，病毒标志物之间的相关性尚未得到充分探讨。
本研究旨在探讨急性乙型肝炎患者和未经治疗的慢性 HBV 感染者中血清 HBV RNA 与其他病毒标志物之间的相关性。
定量检测了 19 例急性乙型肝炎患者和 84 例不同感染阶段未经治疗的慢性 HBV 感染者的血清病毒标志物。采用 Pearson 或 Spearman 相关分析对病毒标志物之间的相关性进行分析。
急性乙型肝炎患者的血清病毒标志物和肝内 cccDNA 水平低于未经治疗的慢性 HBV 感染者。HBeAg 阳性慢性 HBV 感染者中，血清 HBV RNA 水平与血清 HBV DNA、HBsAg 和肝内 cccDNA 水平呈正相关。总血清 HBV 核酸（HBV DNA 加 RNA）在反映肝内 cccDNA 活性方面具有优势。分层分析显示，这些相关性仅见于 HBeAg 阳性慢性乙型肝炎期。此外，在 HBeAg 阴性慢性 HBV 感染期，HBV 聚合酶 RT 区发现高频 R193M 和 P196A 突变，导致血清 HBV DNA 降低和 HBV RNA 升高。
急性乙型肝炎患者的 HBV 复制能力低于慢性 HBV 感染者。在未经治疗的 HBeAg 阳性慢性 HBV 感染者中，血清 HBV DNA 加 RNA 在反映肝内 cccDNA 活性方面优于单独检测任何一种标志物。此外，HBV 聚合酶 RT 区的突变可能导致 HBeAg 阴性慢性 HBV 感染期 HBV 聚合酶的逆转录活性减弱。
