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Real-Time Polymerase Chain Reaction-Based Detection and Quantification of Hepatitis B Virus DNA
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Analysis of precore/core covariances associated with viral kinetics and genotypes in hepatitis B e antigen-positive

Chun-Pei Cheng1, Pei-Fen Lee, Wen-Chun Liu

  • 1Department of Computer Science and Information Engineering, National Cheng Kung University, Tainan, Taiwan.

Plos One
|March 3, 2012
PubMed

Insights

Amino acid changes in Hepatitis B virus (HBV) correlate with viral activity and patient outcomes. Identifying these covariances aids in early treatment decisions for chronic hepatitis B patients.

Area of Science:

  • Virology
  • Immunology
  • Genetics

Background:

  • Hepatitis B virus (HBV) infection can lead to severe liver disease, including cirrhosis and hepatocellular carcinoma.
  • Individual responses to HBV infection, including viral load kinetics and immune responses, are highly variable.
  • Hepatitis B e antigen (HBeAg) and core antigen (HBcAg) are key indicators of active HBV replication.

Purpose of the Study:

  • To identify amino acid covariances within the HBV precore/core open reading frame (ORF) in relation to viral kinetics, seroconversion, and genotypes.
  • To understand the dynamic changes in these covariances over time during chronic HBV infection.
  • To explore the potential of these covariances as biomarkers for predicting disease progression and guiding treatment.

Main Methods:

  • A one-year follow-up study of 23 HBeAg-positive chronic hepatitis B patients.
  • Monthly measurement of serum alanine aminotransferase, HBV DNA, and HBeAg levels for patient subgrouping.
  • Direct sequencing and translation of HBV precore/core ORFs to analyze amino acid sequences and identify time-dependent covariances.
  • Comparison of covariance patterns between different patient subgroups based on viral kinetics, HBeAg seroconversion status, and HBV genotype (B and C).

Main Results:

  • Greater degrees of amino acid covariances were observed in fluctuating viral loads, non-seroconversion of HBeAg, and genotype C infections compared to stable, seroconverting, and genotype B infections.
  • Identified mutation hotspots within covariances were linked to the HBV infection process, with a predominance in genotype C.
  • Covariances were also detected in the early stage of infection, from baseline to peak HBV DNA levels, suggesting potential predictive value.

Conclusions:

  • Amino acid covariances in the HBV precore/core region are significantly associated with viral kinetics, HBeAg seroconversion, and HBV genotype.
  • Representative covariances identified in this study may serve as valuable markers for clinicians to tailor treatment strategies, even in asymptomatic patients during the early stages of HBV infection.

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