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

Abstract

Aim Deletions are observed frequently in the preS1/S2 region of hepatitis B virus (HBV) genome, in association with liver disease advancement. However, the most significant preS1/S2 region and its influences on viral markers are unclear. Methods The preS1/S2 HBV regions of 90 patients without antiviral therapy were subjected to deep sequencing and deleted regions influencing viral markers were investigated. Results From the deletion frequency analysis in each patient, deletions were observed most frequently in the preS2 codon 132–141 region. When the patients were divided into three groups (0–0.1%: n = 27, 0.1%-10%: n = 34, 10–100%: n = 29), based on the deletion frequency, FIB-4 (p < 0.01), HBV DNA (p < 0.01), HBcrAg (p < 0.01) and preS1/S2 start codon mutations (p < 0.01, both) were significantly associated with the deletion. When clinical and viral markers were investigated by multivariate analysis for their association with the deletion, FIB-4 (p < 0.05), HBcrAg (p < 0.05), and preS1 start codon mutation (p < 0.01) were extracted as independent variables. When the influence of the preS codon 132-141deletions on HBsAg and HBcrAg, relative to HBV DNA, was investigated, the HBsAg/HBV DNA ratio was lower (0–10% vs. 10%-100%, p<0.05), while the HBcrAg/HBV DNA rati o was higher (0–0.1% vs. 10%-100%, p<0.05) in the presence of the preS codon 132-141deletions. Conclusion The preS codon.132-141 deletions have a significant influence on the clinical characteristics and viral markers, even when present as a minor population. Importantly, the preS codon 132–141 deletions have a clear influence on the viral life cycle and pathogenesis.