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J Clin Virol. 2018 Jan 6;99-100:71-78. doi: 10.1016/j.jcv.2017.12.016. [Epub ahead of print]
Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naïve HBV-infected individuals.Huang H1, Wang J2, Li W3, Chen R2, Chen X2, Zhang F4, Xu D5, Lu F6.
Author information
1Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China; Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China.2Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China.3Department of clinical laboratory, Beijing Ditan Hospital Capital Medical University, Beijing, China.4Department of Microbiology, Harbin Medical University, Harbin, Heilongjiang, China. Electronic address: [email protected].5Institute of Infectious Disease and Medical center for Liver Failure, Beijing 302 Hospital, Beijing, China. Electronic address: [email protected].6Department of Microbiology & Infectious Disease Center, Peking University Health Science Center, Beijing, China. Electronic address: [email protected].
AbstractBACKGROUND: 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.
OBJECTIVES: 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.
STUDY DESIGN: 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.
RESULTS: 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.
CONCLUSIONS: 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.
Copyright © 2018 Elsevier B.V. All rights reserved.
KEYWORDS: Covalently closed circular DNA; Hepatitis B e antigen; Hepatitis B surface antigen; Hepatitis B virus; Pregenomic RNA
PMID:29353073DOI:10.1016/j.jcv.2017.12.016
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