HBV preS deletion mapping using deep sequencing demonstrates a unique association with viral markers

Area of Science:

• Hepatology
• Virology
• Molecular Biology

Background:

• Deletions in the hepatitis B virus (HBV) preS1/S2 region are frequently observed and linked to advanced liver disease.
• The specific significance of the preS1/S2 region and its impact on viral markers remain incompletely understood.

Purpose of the Study:

• To investigate the most significant preS1/S2 region deletions in HBV.
• To determine the influence of these deletions on various viral and clinical markers in patients without antiviral therapy.

Main Methods:

• Deep sequencing of the preS1/S2 HBV regions from 90 treatment-naive patients.
• Analysis of deletion frequencies and their association with viral markers (FIB-4, HBV DNA, HBcrAg, preS1/S2 start codon mutations).
• Multivariate analysis to identify independent predictors of deletion presence.

Main Results:

• Deletions were most frequent in the preS2 codon 132-141 region.
• FIB-4, HBV DNA, HBcrAg, and preS1/S2 start codon mutations were significantly associated with preS2 codon 132-141 deletions.
• FIB-4, HBcrAg, and preS1 start codon mutations were identified as independent variables influencing deletions.
• The HBsAg/HBV DNA ratio decreased, while the HBcrAg/HBV DNA ratio increased with higher frequencies of preS codon 132-141 deletions.

Conclusions:

• PreS codon 132-141 deletions significantly influence clinical characteristics and viral markers, even as minor populations.
• These deletions play a crucial role in the HBV life cycle and pathogenesis.
• Targeting these deletions could offer insights into HBV disease management.