Hepatitis E virus in developed countries: one of the most successful zoonotic viral diseases in human history?

Until recently, hepatitis E was thought to be largely confined to hyperendemic areas in Asia, Africa and Mexico. Over the last 10 years it has become clear that this is not the case, as it is surprisingly common in developed countries. In these settings, it is caused by HEV genotypes 3 and 4, and is a porcine zoonosis. It causes a range of human illness including acute and chronic hepatitis, and a spectrum of neurological injury. HEV RNA has been found in donated blood from an increasing number of countries, and in some locations with a very high incidence. The clinical phenotype and burden of disease in humans is still emerging. In contrast to previous 'received wisdom', zoonotically transmitted HEV may be one of the most successful zoonotic viral infections in human history. How did we, as a scientific community, get this so badly wrong? This review considers this question from a largely clinical perspective, explores the places HEV has been 'hiding' and the emerging clinical phenotype in humans.