Hepatitis E virus (HEV) is the commonest cause of acute viral hepatitis worldwide
HEV is hyperendemic in many developing countries, where it is spread predominantly by contaminated water, and endemic in developed countries, where it is mostly a porcine zoonosis
HEV is associated with a range of subacute monophasic neurological injuries, in particular, Guillain–Barré syndrome, neuralgic amyotrophy and encephalitis/myelitis
In patients with HEV-associated neurological injury, the neurological features dominate the clinical picture, and hepatitis is either mild or absent
The incidence, clinical phenotype, pathophysiology and treatment of HEV-associated neurological injury remain to be determined
Hepatitis E is hyperendemic in many developing countries in Asia and Africa, and is caused by hepatitis E virus (HEV) genotypes 1 and 2, which are spread via the faecal–oral route by contaminated water. Recent data show that HEV infection is also endemic in developed countries. In such geographical settings, hepatitis E is caused by HEV genotypes 3 and 4, and is mainly a porcine zoonosis. In a minority of cases, HEV causes acute and chronic hepatitis, but infection is commonly asymptomatic or unrecognized. HEV infection is associated with a number of extrahepatic manifestations, including a range of neurological injuries. To date, 91 cases of HEV-associated neurological injury — most commonly, Guillain–Barré syndrome, neuralgic amyotrophy, and encephalitis/myelitis — have been reported. Here, we review the reported cases, discuss possible pathogenic mechanisms, and present our perspectives on future directions and research questions.
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H.R.D. and N.K. have received support from the Gates Foundation. B.C.J. has received support from the Netherlands Organization for Health Research and Development, Erasmus MC and GBS-CIDP Foundation International.
H.R.D. has received travel and accommodation costs and consultancy fees from GlaxoSmithKline, Wantai and Roche; travel, accommodation and lecture fees from Merck, Gilead and GFE Blut; and travel and accommodation fees from the Falk Foundation. N.K. has received travel and accommodation costs and consultancy fees from Novartis and Merck; travel, accommodation and lecture fees from Gilead, Novartis, Astellas, BMS, Amgen and Fresenius. J.J.J.v.E. has received travel and accommodation costs or consultancy or lecture fees from Merck, Biogen Idec, Novartis and Teva Pharmaceutical Industries. B.C.J. has received research support from Prinses Beatrix Spierfonds, CSL-Behring and Grifols, and travel support from Baxter Biopharmaceutics. The other authors declare no competing interests.
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Dalton, H., Kamar, N., van Eijk, J. et al. Hepatitis E virus and neurological injury. Nat Rev Neurol 12, 77–85 (2016). https://doi.org/10.1038/nrneurol.2015.234
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