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BACKGROUND: Since previous studies have investigated the population dynamics of Japan-indigenous genotype 3 hepatitis E virus (HEV) using virus sequences, more nucleotide sequences have been determined, and new techniques have been developed for such analysis. AIMS: To prevent future hepatitis E epidemic in Japan, this study aimed to elucidate the cause of past HEV expansion. METHODS: The epidemic history of Japan-indigenous genotype 3 HEV was determined using the coalescent analysis framework. Bayesian skyline plot (BSP) and Bayesian estimate of phylogeny with relaxed molecular clock models were calculated using Markov chain Monte Carlo sampling. RESULTS: Japan-indigenous strains consist of New World strains (subtype 3a), Japanese strains (3b) and European strains (3e). The oldest lineage, 3b, appeared around 1929. Lineages 3a and 3e appeared around 1960. BSPs indicated similar radical population growth of the 3a and 3b lineages from 1960 to 1980. CONCLUSIONS: Population dynamics of the three lineages shared some common characteristics, but had distinguishing features. The appearance of 3a and 3e lineages coincides with the increase of large-race pig importation from Europe and the USA after 1960. The epidemic phase of 3a and 3b strains from 1960 to 1980 could be related to increased opportunity for HEV infection arising from large-scale pig breeding since 1960. Our observations revealed new findings concerning the close relationship between the epidemic history of Japan-indigenous genotype 3 HEV and the improvement of the Japanese pig industry. Infection control in pig farms should be an effective method of preventing HEV infection in humans.

Original publication




Journal article


Liver Int

Publication Date





675 - 688


Animals, Base Sequence, Bayes Theorem, Colon, Evolution, Molecular, Hepatitis E, Hepatitis E virus, Humans, Japan, Liver, Markov Chains, Models, Genetic, Molecular Sequence Data, Monte Carlo Method, Phylogeny, Population Dynamics, Sequence Analysis, DNA, Species Specificity, Sus scrofa, Viral Proteins