Characterization of genetic mutations in hepatitis B virus isolated from HBsAg+/HBcAb+/HBsAb-/HBV DNA + Japanese blood donors

In Japan, a universal hepatitis B (HB) vaccination was introduced in 2016. Through continuous analysis of HBV DNA mutations, the changes in HBV prevalence before and after the introduction of the universal HB vaccine can be monitored. In this study, we conducted mutational analysis of HBV DNA in HB small protein antigen-positive/HBV core antibody-positive/HB small protein antibody-positive/HBV DNA-positive donor blood samples, with the aim of establishing a baseline prior to the introduction of universal vaccination. We successfully sequenced the full-length HBV DNA in 32 of 33 samples. Immune-escape mutations in the S protein were frequently detected in genotypes B and C. In genotype B, a 1896 nonsense mutation in the precore protein-coding region, which enhances HBV replication and is associated with HB e antigen negativity, was detected at high frequency. In genotype A, the 1858 mutation, which suppresses the 1896 nonsense mutation, was detected at a high frequency. The 1762/1764 double mutation, a risk factor for hepatocellular carcinoma (HCC), was detected frequently in genotype C. These findings provide baseline data and indicate the need for continued monitoring to assess whether universal vaccination influences mutation patterns over time.