Serum HBV DNA plus RNA shows superiority in reflecting the activity of intrahepatic cccDNA in treatment-naive HBV-infected individuals

Background: 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-naive chronic HBV-infected individuals. Study design: The serum viral markers of 19 acute hepatitis B patients and 84 treatment-naive 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-naive 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-naive 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.