Hepatitis E virus: Infection beyond the liver? Sven Pischke, Johannes Hartl, Suzan D. Pas, Ansgar W. Lohse, Bart C. Jacobs, Annemiek A. Van der Eijk  Journal of Hepatology  Volume 66, Issue 5, Pages 1082-1095 (May 2017) DOI: 10.1016/j.jhep.2016.11.016 Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Reported extrahepatic manifestations of HEV infection. The pathogenesis of these manifestations (A) is unknown but we hypothesize mechanisms with (B) or without (C) virus replication at these extrahepatic sites. Local viral replication may damage the infected cells and tissues directly (B) or may trigger an immune response, especially in cases of neuronal damage (C). For example, in GBS, molecular mimicry between infectious agents and peripheral nerve self-antigens may result in nerve injury, although it is unknown if such mechanisms play a role in HEV-related GBS. Other mechanisms by which an immune response to HEV may trigger extrahepatic damage is via induction of other antibodies, T-cells, deposition of HEV-antigens/antibody-immune-complexes or other mediators of inflammation. Journal of Hepatology 2017 66, 1082-1095DOI: (10.1016/j.jhep.2016.11.016) Copyright © 2016 European Association for the Study of the Liver Terms and Conditions

Fig. 2 In immunocompetent patients, HEV-3 rarely causes symptomatic hepatitis but can result in acute fulminant hepatitis with decompensation in patients with underlying chronic liver disease. HEV GT3 and HEV GT4 may lead to chronic infection in patients with an impaired immune response due to illness or medication. Both acute and chronic HEV infections have been associated with extrahepatic manifestations. Currently no vaccine is available other countries than in China. There are no data to suggest whether such a vaccine would protect against HEV (re)infection in immunocompromised patients. Journal of Hepatology 2017 66, 1082-1095DOI: (10.1016/j.jhep.2016.11.016) Copyright © 2016 European Association for the Study of the Liver Terms and Conditions