Naturally occurring deletions/insertions in HBV core promoter tend to decrease in hepatitis B e antigen-positive...

Area of Science:

• Hepatology
• Virology
• Molecular Biology

Background:

• Mutations in the hepatitis B virus (HBV) core promoter (CP) are implicated in viral replication and disease progression.
• Investigated CP deletion/insertion mutations (Del/Ins) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients.

Purpose of the Study:

• To investigate the prevalence and dynamic changes of CP Del/Ins mutations in HBeAg-positive CHB patients before and during antiviral treatment.
• To analyze the impact of these mutations on HBV transcription activities and the hepatitis B X protein (HBx).

Main Methods:

• Detection of CP Del/Ins using direct and clone sequencing in 12 patients, with follow-up to 48 weeks of treatment.
• Luciferase assays to assess promoter activities and sequence comparison for HBx integrity.
• Analysis of 292 untreated HBeAg-positive CHB cases.

Main Results:

• CP Del/Ins mutations were detected in 100% of treated patients at baseline, decreasing to 16.7% by week 48 (P<0.001).
• Mutation prevalence correlated with declines in HBV DNA, HBsAg, ALT, and AST, and increased HBeAg loss.
• Del/Ins mutations affected promoter activity and potentially truncated HBx in 71.8% of sequences; found in 27.4% of untreated cases.

Conclusions:

• Complex CP Del/Ins mutants naturally occur in untreated HBeAg-positive CHB patients.
• These mutations influence HBV transcription and HBx integrity, potentially contributing to disease progression.
• Antiviral therapy reduces the prevalence of CP Del/Ins mutations alongside improvements in clinical markers.