Does HEV-3 subtype play a role in the severity of acute hepatitis E?

Hepatitis E virus genotype 3 (HEV-3) is a major aetiologic agent of acute hepatitis in industrialized countries. Two main HEV-3 subtypes are found in Europe: subtypes 3c and 3f. We have analysed the clinical and biological parameters from 100 French immunocompetent patients with an HEV subtype 3f or subtype 3c infection, included in a prospective multicentre study. Stepwise regression analysis found that infections with HEV subtype 3f were associated with fever (OR: 6.1 95%CI: 1.4-26.1), have a greater virus load (OR: 7.4; 95%CI: 1.3-42.2) and require more frequent hospitalization (OR: 7.6; 95%CI: 1.1-51.4) than those infected with subtype 3c. The directed acyclic graph strengthens the multivariate analyses indicating a direct link between the HEV subtype, HEV RNA concentration, fever and hospitalization. Further studies on patients in other European countries are needed to confirm this relationship and determine the underlying mechanism.