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

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.