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

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 chronica...

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Bibliographic Details
Published in:Virology journal 2022-01, Vol.19 (1), p.22-22, Article 22
Main Authors: Laras, Andreas, Papatheodoridi, Margarita, Panopoulou, Eleni, Papatheodoridis, George V, Hadziyannis, Stephanos J, Hadziyannis, Emilia
Format: Article
Language:English
Subjects:
Analysis
Antigens
Antiviral Agents - therapeutic use
Biomarker
biomarkers
blood serum
Care and treatment
chemical bonding
chronic hepatitis B
Circular DNA
Clinical significance
Diagnosis
DNA, Viral - genetics
Genetic transcription
genotype
Genotype & phenotype
Genotypes
HBeAg negative
HBV RNA
Hepatitis associated antigen
Hepatitis B
hepatitis B antigens
Hepatitis B e antigen
Hepatitis B e Antigens
Hepatitis B virus
Hepatitis B virus - genetics
Hepatitis B, Chronic - drug therapy
Hepatocytes
Humans
Infections
Laboratories
Liver
Liver cells
Lysis
Measurement
Patients
Polymerase chain reaction
Pregenomic RNA
Promoters (Genetics)
relapse
Retrospective Studies
Risk factors
RNA
RNA viruses
therapeutics
Transcription
transcription (genetics)
Treatment discontinuation
Variables
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Summary: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. 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. 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) log 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) log cp/mL, as well as, a significant inverse correlation with the duration of treatment (r = - 0.346, p 
ISSN:1743-422X
1743-422X
DOI:10.1186/s12985-022-01749-7