Population-Based Molecular Surveillance of Hepatitis B Virus Genotypes in the Goto Islands, Japan: A Three Decade Study (1977-2008) of 916 Carriers.

AIMS: Understanding the molecular characteristics and genotype distribution of hepatitis B virus (HBV) is essential to elucidate intra and inter community transmission routes, identify cluster cases, and assess clinical implications based on genotype-specific virulence. This study aimed to investigate HBV genotype distribution in a geographically isolated Japanese islands with high HBV endemicity.

METHODS

From 1977 to 2008, all 34,136 residents of the Kamigoto area in the Goto Islands were screened for HBsAg, identifying 1474 positive cases (4.3%). Among them, 916 stocked serum samples with sufficient volume were randomly selected. HBV DNA levels were quantified using real-time PCR. Genotyping was carried out through nested PCR targeting the overlapping surface-polymerase or surface gene, followed by phylogenetic analysis. Full genome sequencing was conducted on 23 randomly selected samples to identify sub-genotypes.

RESULTS

HBV DNA was detected in 82.9% of participants. Genotyping was successful in 81.8%, revealing predominant genotype C (96.5%), followed by genotypes B (3.1%) and A (0.4%). Phylogenetic analysis identified multiple genotype C clusters, suggesting intra-community transmission. Full genome sequencing confirmed sub-genotypes C2 and B1, closely related to Japanese reference strains. HBV DNA levels were significantly higher in younger age groups (p < 0.0001), with no sex difference.

CONCLUSION

This study presents rare population-based molecular evidence of sustained HBV genotype C2 endemicity and intra-community transmission within a defined setting. The findings underscore clinical significance of implementing targeted area- and population-specific strategies including early detection through screening, linkage to care, vaccination, and long-term surveillance, as an effective model for HBV micro-elimination in high-burden communities.