Secreted hepatitis B virus splice variants differ by HBV genotype and across phases of chronic hepatitis B infection

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Updated: Sep 22, 2025

Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
11:14

Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection

Published on: November 7, 2018

18.5K

Olivia Maslac1,2, Josef Wagner1, Vitina Sozzi1

  • 1Division of Molecular Research and Development, Victorian Infectious Diseases Reference Laboratory, Peter Doherty Institute for Infection and Immunity, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Journal of Viral Hepatitis
|May 18, 2022
PubMed

Insights

Hepatitis B virus (HBV) splice variants vary by genotype and disease phase in chronic hepatitis B (CHB). These variants, particularly Sp1 and Sp13, were more frequent in immune-active phases and associated with lower functional cure rates.

Area of Science:

  • Virology
  • Hepatology
  • Genomics

Background:

  • Chronic hepatitis B (CHB) involves distinct phases of hepatitis B virus (HBV) infection.
  • HBV splice variants, though not essential for replication, are increasingly linked to liver disease progression.
  • Previous studies lacked data on HBV splice variant diversity across genotypes and CHB phases.

Purpose of the Study:

  • To investigate the frequency and diversity of HBV splice variants in CHB patients.
  • To analyze variants across different HBV genotypes (A, B, C, D) and CHB phases (I, II, IV).
  • To explore the association of splice variants with clinical outcomes like HBeAg levels and HBsAg loss.

Main Methods:

  • Analysis of next-generation sequencing data from 404 CHB patient samples.
  • Utilized an in-house bioinformatics pipeline to identify HBV splice variants.
  • Categorized samples by HBV genotype and CHB phase (I, II, IV).

Main Results:

  • HBV splice variants showed significant differences in frequency and type based on genotype and CHB phase.
  • Splice variant Sp1 was detected in 51% of patients, followed by Sp13 in 37%.
  • Variant frequency was highest in Phase II (75%) and Phase I (70%), associated with immune activation.
  • Sp1 and Sp13 were linked to reduced HBeAg levels and lower likelihood of HBsAg loss (functional cure) in Phase II patients.

Conclusions:

  • HBV splice variant prevalence differs significantly by HBV genotype and CHB phase.
  • Increased detection of splice variants in Phase II warrants further investigation due to its association with immune activity.
  • Findings highlight the clinical relevance of HBV splice variants in CHB pathogenesis and treatment outcomes.

Keywords:
chronic hepatitis Bhepatitis B surface antigensplicing

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