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Hepatitis E virus and neurological injury

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.

References

  1. Kamar, N. et al. Hepatitis E. Lancet 379, 2477–2488 (2012).

    Article  PubMed  Google Scholar 

  2. Dalton, H. R., Bendall, R., Ijaz, S. & Banks, M. Hepatitis E: an emerging infection in developed countries. Lancet Infect. Dis. 8, 698–709 (2008).

    Article  PubMed  Google Scholar 

  3. Kamar, N., Dalton, H. R., Abravanel, F. & Izopet, J. Hepatitis E virus infection. Clin. Microbiol. Rev. 27, 116–138 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Woolson, K. L. et al. Extra-hepatic manifestations of autochthonous hepatitis E infection. Aliment. Pharmacol. Ther. 40, 1282–1291 (2014).

    Article  CAS  PubMed  Google Scholar 

  5. Dalton, H. R. et al. Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease. Eur. J. Gastroenterol. Hepatol. 20, 784–790 (2008).

    Article  CAS  PubMed  Google Scholar 

  6. Dalton, H. R. et al. Autochthonous hepatitis E in southwest England. J. Viral Hepat. 14, 304–309 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Ijaz, S. et al. Non-travel-associated hepatitis E in England and Wales: demographic, clinical, and molecular epidemiological characteristics. J. Infect. Dis. 192, 1166–1172 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Mansuy, J. M. et al. Hepatitis E in the south west of France in individuals who have never visited an endemic area. J. Med. Virol. 74, 419–424 (2004).

    Article  PubMed  Google Scholar 

  9. Tsang, T. H. et al. Acute hepatitis E infection acquired in California. Clin. Infect. Dis. 30, 618–619 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Pina, S., Buti, M., Cotrina, M., Piella, J. & Girones, R. HEV identified in serum from humans with acute hepatitis and in sewage of animal origin in Spain. J. Hepatol. 33, 826–833 (2000).

    Article  CAS  PubMed  Google Scholar 

  11. Sainokami, S. et al. Epidemiological and clinical study of sporadic acute hepatitis E caused by indigenous strains of hepatitis E virus in Japan compared with acute hepatitis A. J. Gastroenterol. 39, 640–648 (2004).

    Article  PubMed  Google Scholar 

  12. Widdowson, M. A. et al. Cluster of cases of acute hepatitis associated with hepatitis E virus infection acquired in the Netherlands. Clin. Infect. Dis. 36, 29–33 (2003).

    Article  PubMed  Google Scholar 

  13. Kamar, N. et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N. Engl. J. Med. 358, 811–817 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Gerolami, R., Moal, V. & Colson, P. Chronic hepatitis E with cirrhosis in a kidney-transplant recipient. N. Engl. J. Med. 358, 859–860 (2008).

    Article  CAS  PubMed  Google Scholar 

  15. Kamar, N. et al. Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. Gastroenterology 140, 1481–1489 (2011).

    Article  PubMed  Google Scholar 

  16. Dalton, H. R., Bendall, R., Keane, F., Tedder, R. & Ijaz, S. Persistent carriage of hepatitis E virus in patients with HIV infection. N. Engl. J. Med. 361, 1025–1027 (2009).

    Article  CAS  PubMed  Google Scholar 

  17. Zaaijer, H. L. No artifact, hepatitis E is emerging. Hepatology 62, 654 (2014).

    Article  Google Scholar 

  18. Slot, E. et al. Silent hepatitis E virus infection in Dutch blood donors, 2011 to 2012. Euro Surveill. 18, 20550 (2013).

    Article  PubMed  Google Scholar 

  19. Gallian, P. et al. Hepatitis E virus infections in blood donors, France. Emerg. Infect. Dis. 20, 1914–1917 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Mansuy, J. M. et al. Hepatitis E virus antibody in blood donors, France. Emerg. Infect. Dis. 17, 2309–2312 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Vollmer, T. et al. Novel approach for detection of hepatitis E virus infection in German blood donors. J. Clin. Microbiol. 50, 2708–2713 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Baylis, S. A., Gartner, T., Nick, S., Ovemyr, J. & Blumel, J. Occurrence of hepatitis E virus RNA in plasma donations from Sweden, Germany and the United States. Vox Sang. 103, 89–90 (2012).

    Article  CAS  PubMed  Google Scholar 

  23. Wenzel, J. J., Preiss, J., Schemmerer, M., Huber, B. & Jilg, W. Test performance characteristics of anti-HEV IgG assays strongly influence hepatitis E seroprevalence estimates. J. Infect. Dis. 207, 497–500 (2013).

    Article  CAS  PubMed  Google Scholar 

  24. Fukuda, S. et al. Prevalence of antibodies to hepatitis E virus among Japanese blood donors: identification of three blood donors infected with a genotype 3 hepatitis E virus. J. Med. Virol. 73, 554–561 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Guo, Q. S. et al. Prevalence of hepatitis E virus in Chinese blood donors. J. Clin. Microbiol. 48, 317–318 (2010).

    Article  PubMed  Google Scholar 

  26. Hewitt, P. E. et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet 384, 1766–1773 (2014).

    Article  PubMed  Google Scholar 

  27. Ijaz, S., Szypulska, R., Tettmar, K. I., Kitchen, A. & Tedder, R. S. Detection of hepatitis E virus RNA in plasma mini-pools from blood donors in England. Vox Sang. 102, 272 (2012).

    Article  CAS  PubMed  Google Scholar 

  28. Beale, M. A., Tettmar, K., Szypulska, R., Tedder, R. S. & Ijaz, S. Is there evidence of recent hepatitis E virus infection in English and North Welsh blood donors? Vox Sang. 100, 340–342 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Fischer, C. et al. Seroprevalence and incidence of hepatitis E in blood donors in Upper Austria. PLoS ONE 10, e0119576 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Xu, C. et al. An assessment of hepatitis E virus (HEV) in US blood donors and recipients: no detectable HEV RNA in 1939 donors tested and no evidence for HEV transmission to 362 prospectively followed recipients. Transfusion 53, 2505–2511 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Cleland, A. et al. Hepatitis E virus in Scottish blood donors. Vox Sang. 105, 283–289 (2013).

    Article  CAS  PubMed  Google Scholar 

  32. Shrestha, A. C. et al. Hepatitis E virus and implications for blood supply safety, Australia. Emerg. Infect. Dis. 20, 1940–1942 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Dalton, H. R. et al. Hepatitis E in New Zealand. J. Gastroenterol. Hepatol. 22, 1236–1240 (2007).

    Article  PubMed  Google Scholar 

  34. Halliday, J. S. et al. Hepatitis E virus infection, Papua New Guinea, Fiji, and Kiribati, 2003–2005. Emerg. Infect. Dis. 20, 1057–1058 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Faramawi, M. F., Johnson, E., Chen, S. & Pannala, P. R. The incidence of hepatitis E virus infection in the general population of the USA. Epidemiol. Infect. 139, 1145–1150 (2011).

    Article  CAS  PubMed  Google Scholar 

  36. Legrand-Abravanel, F. et al. Characteristics of autochthonous hepatitis E virus infection in solid-organ transplant recipients in France. J. Infect. Dis. 202, 835–844 (2010).

    Article  CAS  PubMed  Google Scholar 

  37. Sood, A., Midha, V. & Sood, N. Guillain–Barré syndrome with acute hepatitis E. Am. J. Gastroenterol. 95, 3667–3668 (2000).

    CAS  PubMed  Google Scholar 

  38. Kejariwal, D., Roy, S. & Sarkar, N. Seizure associated with acute hepatitis E. Neurology 57, 1935 (2001).

    Article  CAS  PubMed  Google Scholar 

  39. Kamani, P. et al. Guillain–Barré syndrome associated with acute hepatitis E. Indian J. Gastroenterol. 24, 216 (2005).

    PubMed  Google Scholar 

  40. Dixit, V. K., Abhilash, V. B., Kate, M. P. & Jain, A. K. Hepatitis E infection with Bell's palsy. J. Assoc. Physicians India 54, 418 (2006).

    CAS  PubMed  Google Scholar 

  41. Mandal, K. & Chopra, N. Acute transverse myelitis following hepatitis E virus infection. Indian Pediatr. 43, 365–366 (2006).

    PubMed  Google Scholar 

  42. Joshi, G. G. et al. Acute viral hepatitis E and Japanese encephalitis: an unusual co-occurrence. Indian J. Gastroenterol. 26, 102–103 (2007).

    PubMed  Google Scholar 

  43. Fong, F. & Illahi, M. Neuralgic amyotrophy associated with hepatitis E virus. Clin. Neurol. Neurosurg. 111, 193–195 (2009).

    Article  PubMed  Google Scholar 

  44. Loly, J. P. et al. Guillain–Barré syndrome following hepatitis E. World J. Gastroenterol. 15, 1645–1647 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Rianthavorn, P. et al. The entire genome sequence of hepatitis E virus genotype 3 isolated from a patient with neuralgic amyotrophy. Scand. J. Infect. Dis. 42, 395–400 (2010).

    Article  CAS  PubMed  Google Scholar 

  46. Kamar, N. et al. Hepatitis E virus and neurologic disorders. Emerg. Infect. Dis. 17, 173–179 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Kamar, N. et al. Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis. Am. J. Transplant. 10, 1321–1324 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. Dalton, H., Keane, F., Bendall, R., Mathew, J. & Ijaz, S. Treatment of chronic hepatitis E in a HIV positive patient. Ann. Intern. Med. 155, 479–480 (2011).

    Article  PubMed  Google Scholar 

  49. Cronin, S., McNicholas, R., Kavanagh, E., Reid, V. & O'Rourke, K. Anti-glycolipid GM2-positive Guillain–Barré syndrome due to hepatitis E infection. Ir. J. Med. Sci. 180, 255–257 (2011).

    Article  CAS  PubMed  Google Scholar 

  50. Maurissen, I., Jeurissen, A., Strauven, T., Sprengers, D. & De Schepper, B. First case of anti-ganglioside GM1-positive Guillain–Barré syndrome due to hepatitis E virus infection. Infection 40, 323–326 (2012).

    Article  CAS  PubMed  Google Scholar 

  51. Despierres, L. A. et al. Neurologic disorders and hepatitis E, France, 2010. Emerg. Infect. Dis. 17, 1510–1512 (2011).

    PubMed  PubMed Central  Google Scholar 

  52. Del Bello, A., Arne-Bes, M. C., Lavayssiere, L. & Kamar, N. Hepatitis E virus-induced severe myositis. J. Hepatol. 57, 1152–1153 (2012).

    Article  PubMed  Google Scholar 

  53. Tse, A. C., Cheung, R. T., Ho, S. L. & Chan, K. H. Guillain–Barré syndrome associated with acute hepatitis E infection. J. Clin. Neurosci. 19, 607–608 (2012).

    Article  PubMed  Google Scholar 

  54. Inghilleri, M. L., Grini Mazouzi, M. & Juntas Morales, R. Neuralgic amyotrophy as a manifestation of hepatitis E infection. Rev. Neurol. (Paris) 168, 383–384 (in French) (2012).

    Article  Google Scholar 

  55. Sharma, B., Nagpal, K., Bakki Sannegowda, R. & Prakash, S. Hepatitis E with Gullain–Barré syndrome: still a rare association. J. Neurovirol. 19, 186–187 (2013).

    Article  PubMed  Google Scholar 

  56. Santos, L. et al. Acute hepatitis E complicated by Guillain–Barré syndrome in Portugal, December 2012 — a case report. Euro Surveill. 18, 20563 (2013).

    Article  PubMed  Google Scholar 

  57. Motte, A., Franques, J., Weitten, T. & Colson, P. Hepatitis E-associated Parsonage–Turner syndrome, France. Clin. Res. Hepatol. Gastroenterol. 38, e11–e14 (2014).

    Article  PubMed  Google Scholar 

  58. Moisset, X. et al. Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E. F1000Res. 2, 259 (2013).

    Article  PubMed  Google Scholar 

  59. Maddukuri, V. C. et al. Chronic hepatitis E with neurologic manifestations and rapid progression of liver fibrosis in a liver transplant recipient. Dig. Dis. Sci. 58, 2413–2416 (2013).

    Article  PubMed  Google Scholar 

  60. Geurtsvankessel, C. H. et al. Hepatitis E and Guillain–Barré syndrome. Clin. Infect. Dis. 57, 1369–1370 (2013).

    Article  PubMed  Google Scholar 

  61. de Vries, M. A., Samijn, J. P., de Man, R. & Boots, J. M. Hepatitis E-associated encephalopathy in a renal transplant recipient. BMJ Case Rep. http://dx.doi.org/10.1136/bcr-2014-204244 (2014).

  62. Comont, T. et al. Acute hepatitis E infection associated with Guillain–Barré syndrome in an immunocompetent patient. Rev. Med. Interne 35, 333–336 (in French) (2014).

    Article  CAS  PubMed  Google Scholar 

  63. Scharn, N. et al. Guillain–Barré syndrome associated with autochthonous infection by hepatitis E virus subgenotype 3c. Infection 42, 171–173 (2014).

    Article  CAS  PubMed  Google Scholar 

  64. Deroux, A. et al. Association between hepatitis E and neurological disorders: two case studies and literature review. J. Clin. Virol. 60, 60–62 (2014).

    Article  CAS  PubMed  Google Scholar 

  65. Belbezier, A., Deroux, A., Sarrot-Reynauld, F., Larrat, S. & Bouillet, L. Myasthenia gravis associated with acute hepatitis E infection in immunocompetent woman. Emerg. Infect. Dis. 20, 908–910 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Chen, X. D., Zhou, Y. T., Zhou, J. J., Wang, Y. W. & Tong, D. M. Guillain–Barré syndrome and encephalitis/encephalopathy of a rare case of Northern China acute severe hepatitis E infection. Neurol. Sci. 35, 1461–1463 (2014).

    Article  PubMed  Google Scholar 

  67. van den Berg, B. et al. Guillain–Barré syndrome associated with preceding hepatitis E virus infection. Neurology 82, 491–497 (2014).

    Article  CAS  PubMed  Google Scholar 

  68. van Eijk, J. J. et al. Neuralgic amyotrophy and hepatitis E virus infection. Neurology 82, 498–503 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Bennett, S., Gunson, R. N. & Li, K. Hepatitis E virus infection presenting with paraesthesia. Scott. Med. J. 60, e27–e29 (2015).

    Article  PubMed  Google Scholar 

  70. Blasco Perrin, H. et al. Neurologic disorders in non-immunocompromized patients with auotchtonous acute hepatitis E. Emerg. Infect. Dis. 21, 1928–1934 (2015).

    PubMed  PubMed Central  Google Scholar 

  71. Décard, B. F. et al. Hepatitis-E virus associated neuralgic amyotrophy with sustained plexus brachialis swelling visualized by high-resolution ultrasound. J. Neurol. Sci. 351, 208–210 (2015).

    Article  PubMed  Google Scholar 

  72. Theochari, E., Vincent-Smith, L. & Ellis, C. Neuralgic amyotrophy complicating acute hepatitis E infection: a rare association. BMJ Case Rep. http://dx.doi.org/10.1136/bcr-2014-207669 (2015).

  73. Jha, A. K., Nijhawan, S., Nepalia, S. & Suchismita, A. Association of Bell's palsy with hepatitis E virus infection: a rare entity. J. Clin. Exp. Hepatol. 2, 88–90 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Carli, P. et al. Shoulder pain in a 30-year-old man. Rev. Med. Interne 33, 111–114 (in French) (2012).

    Article  CAS  PubMed  Google Scholar 

  75. Cheung, M. C., Maguire, J., Carey, I., Wendon, J. & Agarwal, K. Hepatitis E — an unexpected problem at home. Scand. J. Gastroenterol. 47, 253 (2012).

    Article  CAS  PubMed  Google Scholar 

  76. Peri, A. M., Milazzo, L., Meroni, L. & Antinori, S. Radiculoneuropathy associated with acute hepatitis E. Dig. Liver Dis. 45, 963–964 (2013).

    Article  PubMed  Google Scholar 

  77. Martínez Rodríguez, L., Carvajal, P. & Morís, G. Neuralgic amyotrophy associated to hepatitis E virus infection. Med. Clin. (Barc.) 145, 462–463 (in Spanish) (2015).

    Article  Google Scholar 

  78. Dartevel, A. et al. Hepatitis E and neuralgic amyotrophy: five cases and review of literature. J. Clin. Virol. 69, 156–164 (2015).

    Article  PubMed  Google Scholar 

  79. Fokke, C. et al. Diagnosis of Guillain–Barré syndrome and validation of Brighton criteria. Brain 137, 33–43 (2014).

    Article  PubMed  Google Scholar 

  80. Jacobs, B. C. et al. The spectrum of antecedent infections in Guillain–Barré syndrome: a case–control study. Neurology 51, 1110–1115 (1998).

    Article  CAS  PubMed  Google Scholar 

  81. Oomes, P. G., van der Meche, F. G. & Kleyweg, R. P. Liver function disturbances in Guillain–Barré syndrome: a prospective longitudinal study in 100 patients. Dutch Guillain–Barré Study Group. Neurology 46, 96–100 (1996).

    Article  CAS  PubMed  Google Scholar 

  82. van Alfen, N. Clinical and pathophysiological concepts of neuralgic amyotrophy. Nat. Rev. Neurol. 7, 315–322 (2011).

    Article  CAS  PubMed  Google Scholar 

  83. van Alfen, N. & van Engelen, B. G. The clinical spectrum of neuralgic amyotrophy in 246 cases. Brain 129, 438–450 (2006).

    Article  PubMed  Google Scholar 

  84. Yazaki, Y. et al. Characteristics of 20 patients with autochthonous acute hepatitis E in Hokkaido, Japan: first report of bilateral facial palsy following the infection with genotype 4 hepatitis E virus. Tohoku J. Exp. Med. 236, 263–271 (2015).

    Article  PubMed  Google Scholar 

  85. Legrand-Abravanel, F. et al. Hepatitis E virus genotype 3 diversity, France. Emerg. Infect. Dis. 15, 110–114 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  86. Nemni, R. et al. Peripheral neuropathy in hepatitis C virus infection with and without cryoglobulinaemia. J. Neurol. Neurosurg. Psychiatry 74, 1267–1271 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Authier, F. J. et al. Detection of genomic viral RNA in nerve and muscle of patients with HCV neuropathy. Neurology 60, 808–812 (2003).

    Article  PubMed  Google Scholar 

  88. Cacoub, P., Saadoun, D., Limal, N., Leger, J. M. & Maisonobe, T. Hepatitis C virus infection and mixed cryoglobulinaemia vasculitis: a review of neurological complications. AIDS 19, S128–S134 (2005).

    Article  PubMed  Google Scholar 

  89. Shukla, P. et al. Adaptation of a genotype 3 hepatitis E virus to efficient growth in cell culture depends on an inserted human gene segment acquired by recombination. J. Virol. 86, 5697–5707 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Yuki, N. et al. Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain–Barré syndrome. Proc. Natl Acad. Sci. USA 101, 11404–11409 (2004).

    Article  CAS  PubMed  Google Scholar 

  91. Plomp, J. J. & Willison, H. J. Pathophysiological actions of neuropathy-related anti-ganglioside antibodies at the neuromuscular junction. J. Physiol. 587, 3979–3999 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. van Alfen, N. et al. Incidence of neuralgic amyotrophy (Parsonage Turner syndrome) in a primary care seting — a prospective cohort study. PLoS ONE 10, e0128361 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Bendall, R., Ellis, V., Ijaz, S., Ali, R. & Dalton, H. A comparison of two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developed countries. J. Med. Virol. 82, 799–805 (2010).

    Article  CAS  PubMed  Google Scholar 

  94. French Cooperative Group on Plasma Exchange in Guillain–Barré syndrome. Efficiency of plasma exchange in Guillain–Barré syndrome: role of replacement fluids. Ann. Neurol. 22, 753–761 (1987).

  95. Hughes, R. A. & Cornblath, D. R. Guillain–Barré syndrome. Lancet 366, 1653–1666 (2005).

    Article  CAS  PubMed  Google Scholar 

  96. van Eijk, J. J. et al. Evaluation of prednisolone treatment in the acute phase of neuralgic amyotrophy: an observational study. J. Neurol. Neurosurg. Psychiatry 80, 1120–1124 (2009).

    Article  CAS  PubMed  Google Scholar 

  97. van Alfen, N., van Engelen, B. G. & Hughes, R. A. Treatment for idiopathic and hereditary neuralgic amyotrophy (brachial neuritis). Cochrane Database Syst. Rev. 3, CD006976 (2009).

    Google Scholar 

  98. Fourquet, E. et al. Severe thrombocytopenia associated with acute autochthonous hepatitis E. J. Clin. Virol. 48, 73–74 (2010).

    Article  CAS  PubMed  Google Scholar 

  99. Pischke, S., Behrendt, P., Manns, M. P. & Wedemeyer, H. HEV-associated cryoglobulinaemia and extrahepatic manifestations of hepatitis E. Lancet Infect. Dis. 14, 678–679 (2014).

    Article  PubMed  Google Scholar 

  100. Kamar, N. et al. Hepatitis E virus and the kidney in solid-organ-transplant patients. Transplantation 93, 617–623 (2012).

    PubMed  Google Scholar 

  101. Deniel, C. et al. Acute pancreatitis: a rare complication of acute hepatitis E. J. Clin. Virol. 51, 202–204 (2011).

    Article  PubMed  Google Scholar 

  102. Serratrice, J. et al. Acute polyarthritis revealing hepatitis E. Clin. Rheumatol. 26, 1973–1975 (2007).

    Article  PubMed  Google Scholar 

  103. Dumoulin, F. L. & Liese, H. Acute hepatitis E virus infection and autoimmune thyroiditis: yet another trigger? BMJ Case Rep. http://dx.doi.org/10.1136/bcr.12.2011.5441 (2012).

  104. Hoofnagle, J. H., Nelson, K. & Purcell, R. H. Hepatitis E. N. Engl. J. Med. 367, 1237–1244 (2012).

    Article  CAS  PubMed  Google Scholar 

  105. Rein, D. B., Stevens, G. A., Theaker, J., Wittenborn, J. S. & Wiersma, S. T. The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology 55, 988–997 (2012).

    Article  PubMed  Google Scholar 

  106. Stramer, S. L. et al. Hepatitis E virus: seroprevalence and frequency of viral RNA detection among US blood donors. Transfusion http://dx.doi.org/10.1111/trf.13355 (2015).

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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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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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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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