Beyond the liver: the broadened tissue tropism of hepatitis E virus

Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis, yet the virus has been associated with extrahepatic complications, including neurological and renal disorders. These extrahepatic manifestations pose challenges for the diagnosis and treatment of HEV and are considered a reservoir for disease relapse. In addition to recent in vivo patient data, several animal and in vitro models have been established in the last few years, confirming the broad HEV tissue tropism. However, it remains unclear whether extrahepatic complications arise from viral replication within the tissue or from immune-mediated effects. This article highlights current knowledge on the detection of HEV in extrahepatic tissues, with a focus on active HEV replication in humans and animal models.