How genetic variability of hepatitis E virus (VHE) may impact its clinical relevance and transmission

Hepatitis E virus is the main cause of acute hepatitis worldwide. The dichotomy between waterborne human-restricted genotypes 1 and 2 circulating in developing countries and zoonotic genotypes 3 and 4 infecting human through consumption of contaminated meat in industrialized countries is currently discussed, with the detection of HEV in waters of industrialized nations. Chronic infections are described in immunocomprommised patients, as well as extra hepatic syndromes. In vivo and in vitro data have shown that HEV genetic variability can impact the bioclinical relevance of the infection, by highlighting mutations associated with severity. Genetic variability has also to be considered when exploring transmission ways, with the description of new animal reservoirs and new strains able to infect humans. HEV genetic variability is one of the keys to better control its transmission and to adapt diagnostic tools and strategies, with the aim to protect vulnerable populations.