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  • Review Article
  • Published:

Hepatitis E virus and neurological injury

Nature Reviews Neurology volume 12, pages 77–85 (2016)Cite this article

Subjects

Key Points

  • 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

Abstract

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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Figure 1
Figure 2: Brachial plexograms of eight patients with hepatitis E virus-associated neuralgic amyotrophy.

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Acknowledgements

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.

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Authors and Affiliations

  1. Royal Cornwall Hospital, University of Exeter, Penventinnie Lane, Truro, TR1 3LJ, UK

    Harry R. Dalton, Brendan N. Mclean & Richard P. Bendall

  2. European Centre for Environment & Human Health, University of Exeter, Penventinnie Lane, Truro, TR1 3LJ, UK

    Harry R. Dalton & Richard P. Bendall

  3. Departments of Nephrology and Organ Transplantation, CHU Rangueil, INSERM U1043, IFR–BMT, Université Paul Sabatier, 1 Avenue J. Poulhès, Toulouse, Cedex 9, France

    Nassim Kamar

  4. Department of Neurology, Jeroen Bosch Ziekenhuis (JBZ), Henri Dunantstraat 1, 's-Hertogenbosch, 5223 GZ, Netherlands

    Jeroen J. J. van Eijk

  5. Department of Neurology, Pierre Paul Riquet Hospital, CHU Purpan, Place du Dr Baylac, Toulouse, 31059, France

    Pascal Cintas

  6. Department of Neurology/Neuro-Immunology Erasmus MC, Erasmus MC, Afdeling Neurologie, Kamer EE 2287, Postbus 2040, Rotterdam, 3000 CA, Netherlands

    Bart C. Jacobs

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Contributions

H.R.D., N.K., J.J.J.v.E., R.P.B., P.C., B.N.M., and B.C.J. researched data for the article, made substantial contributions to discussion of the content, wrote the article, and reviewed and/or edited the manuscript before submission. H.R.D. drafted the tables. N.K. drafted the supplementary table, and J.J.J.v.E. drafted the figures.

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Correspondence to Harry R. Dalton.

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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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Review – neurological manifestations associated with HEV (DOCX 71 kb)

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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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