A prospective study characterizing full-length hepatitis B virus genomes during acute exacerbation

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Chronic hepatitis B involves rapid Hepatitis B virus (HBV) evolution.
• HBV variation is a potential trigger for acute exacerbations.

Purpose of the Study:

• To investigate the relationship between HBV evolution and acute exacerbations in chronic hepatitis B patients.
• To analyze full-length HBV sequences before, during, and after exacerbation events.

Main Methods:

• Prospective study of 14 chronic hepatitis B patients experiencing exacerbations.
• Monthly monitoring of alanine aminotransferase (ALT) and HBV DNA levels.
• Full-length HBV genome sequencing at various stages (baseline, viral load peak, ALT peak, post-ALT peak) and in vitro replication assays.

Main Results:

• All exacerbations showed an increase in serum viral load, preceding ALT peak in 93% of patients.
• At virologic peak, 86% of patients had HBV genomes identical to baseline.
• Significant nucleotide changes in HBV genomes were observed at and after ALT peak (4.4 and 8.1 mean changes, respectively).
• Emergent HBV variants post-exacerbation exhibited replication potential equivalent to baseline strains.

Conclusions:

• Most acute exacerbations are initiated by an increase in the existing HBV strain.
• Immune selection likely drives the emergence of distinct HBV variants after exacerbation in approximately half of the patients.