Epidemiological Profiles of Hepatitis B Virus Genotypes Among 1–69‐year‐olds in the Mainland of China

ABSTRACT Hepatitis B virus (HBV) exhibits significant genetic diversity affecting clinical outcomes and interventions. Utilizing 4326 HBsAg‐positive samples from China's 2020 national serosurvey (91 896 participants), we successfully sequenced S genes from 3311 specimens. Genotypes/subgenotypes were determined through maximum likelihood phylogeny; serotypes followed Purdy's method. Demographic, serological, and regional associations were analyzed by chi‐square tests. Five HBV genotypes were identified: B (63.91%), C (22.80%), CD (10.48%), D (2.45%) and I (0.36%), plus 15 subgenotypes (B2 dominant, 61.73%). Four serotypes emerged: adw (60.65%), adr (24.37%), ayw (14.53%), and ayr (0.33%), with 10 subserotypes (adw2 dominant, 58.86%). Genotype B predominated East/Central/South China; C prevailed in North/Northeast China. Southwest/Northwest China showed co‐circulation, with CD predominant in Southwest and D in Northwest China. B2 comprised 96.60% of genotype B; adw2 represented 97.06% of adw. Genotype distribution showed significant regional variation and strong associations with gender, age, ethnicity, serological profile, viral load, and serotype (all p < 0.05). HBV in China exhibits marked genetic heterogeneity characterized by distinct regional and population patterns. These findings underscore the necessity for tailored prevention strategies and optimized diagnostics/vaccines to address region‐specific HBV diversity.