Genetic and molecular variants of hepatitis B virus: Implications for disease progression, treatment resistance, and vaccine efficacy

The hepatitis B virus genome exhibits remarkable genetic diversity arising from error-prone reverse transcription, continuous viral evolution, recombination, and quasispecies formation, with important implications for viral persistence, disease progression, therapeutic response, and vaccine performance. The virus is currently classified into at least ten genotypes (A–J) and numerous subgenotypes that exhibit distinct geographic distributions and differences in viral replication, antigen expression, clinical outcomes, and susceptibility to treatment. Naturally occurring mutations within the basal core promoter, precore, polymerase, pre-S/S, and X gene regions further influence viral fitness, immune escape, antiviral resistance, diagnostic performance, and hepatocarcinogenesis. Advances in molecular epidemiology and genomic sequencing continue to improve understanding of hepatitis B virus genetic diversity and its clinical implications, providing a foundation for more effective prevention, diagnosis, therapeutic strategies, and global disease control.