Classification of hepatitis A virus in clades based on VP1/2A region allows higher geographic and temporal resolution than conventional genotyping: a global sequences analysis

Infections caused by the Hepatitis A virus (HAV) occur worldwide. Molecular epidemiology is crucial to understanding the transmission dynamics; however, the current genotype assignment fails to provide useful epidemiologic information. We classified HAV sequences available in GenBank based on 460 bp of the VP1/2A region in clades. Additionally, we associated the site of isolation of the strains with the country’s HAV endemicity. We analyzed 1369 sequences available in GenBank up to December 2023 which fulfilled inclusion criteria for our study. The collection date ranged from 1957 to 2023, and genotypes IA (n = 986) and IB (n = 290) comprised the majority of sequences. Sequences were assigned to 70 different clades; sequences from most clades (n = 36) were detected in one country or a few countries within a single continent, while sequences of only 9 clades were detected in more than two continents. Countries with lower HAV endemicity showed higher diversity of clades compared with countries with higher HAV endemicity. In addition, multinational HAV outbreaks were associated with specific clades. In conclusion, characterization of HAV strains below the genotype level should be helpful to analyze transmission patterns within and between countries.