AbstractIn Japan, hepatitis E had long been considered to be a rare liver disease which can be accidentally
imported from endemic countries in Asia and Africa, where the sanitation conditions are suboptimal. However, since the identification of the first autochthonous hepatitis E case and HEV-viremic domestic pigs in Japan in 2001, our understanding of HEV infection in this country has been changing markedly. This has largely been due to the development of serological and gene-based diagnostic assays, the accumulation of molecular epidemiological findings on HEV infection in humans and animals (as potential reservoirs for HEV in humans) and the recognition of the importance of zoonotic food-borne and other routes of transmission of HEV, including blood-borne transmission. Although it is now evident that autochthonous hepatitis E in Japan is far more common than was previously thought, clinical and subclinical HEV infections indigenous to Japan remain underdiagnosed and their prevalence is still underestimated due to the presence of unknown transmission routes and a low awareness of the infection status by many physicians in Japan. This review focuses on the features of HEV infection in humans and animals, as definitive or potential reservoirs for HEV, in Japan, and updates the current knowledge on the routes of transmission, including zoonotic routes, which are important for the maintenance and spread of HEV in Japan.