Hepatitis E virus infection

Abstract

Hepatitis E virus (HEV) infection can lead to acute and chronic hepatitis as well as to extrahepatic manifestations such as neurological and renal disease; it is the most common cause of acute viral hepatitis worldwide. Four genotypes are responsible for most infection in humans, of which HEV genotypes 1 and 2 are obligate human pathogens and HEV genotypes 3 and 4 are mostly zoonotic. Until quite recently, HEV was considered to be mainly responsible for epidemics of acute hepatitis in developing regions owing to contamination of drinking water supplies with human faeces. However, HEV is increasingly being recognized as endemic in some developed regions. In this setting, infections occur through zoonotic transmission or contaminated blood products and can cause chronic hepatitis in immunocompromised individuals. HEV infections can be diagnosed by measuring anti-HEV antibodies, HEV RNA or viral capsid antigen in blood or stool. Although an effective HEV vaccine exists, it is only licensed for use in China. Acute hepatitis E is usually self-limiting and does not require specific treatment. Management of immunocompromised individuals involves lowering the dose of immunosuppressive drugs and/or treatment with the antiviral agent ribavirin.

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Figure 1: Worldwide presence of HEV genotypes.
Figure 2: HEV genome.
Figure 3: HEV life cycle.
Figure 4: HEV infection and hepatitis E.
Figure 5: Diagnostic algorithm for HEV infection.
Figure 6: Treatment algorithm for immunocompromised patients who received solid organ transplantation.

References

  1. 1

    Balayan, M. S. et al. Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology 20, 23–31 (1983).

    Google Scholar 

  2. 2

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

    Google Scholar 

  3. 3

    Maila, H. T., Bowyer, S. M. & Swanepoel, R. Identification of a new strain of hepatitis E virus from an outbreak in Namibia in 1995. J. Gen. Virol. 85, 89–95 (2004).

    Google Scholar 

  4. 4

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

    Google Scholar 

  5. 5

    Hartl, J. et al. Hepatitis E seroprevalence in Europe: a meta-analysis Viruses 8, 211 (2016).

    Google Scholar 

  6. 6

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

    Google Scholar 

  7. 7

    Aggarwal, R. Hepatitis E: historical, contemporary and future perspectives. J. Gastroenterol. Hepatol. 26 (Suppl. 1), 72–82 (2011).

    Google Scholar 

  8. 8

    Okamoto, H. Genetic variability and evolution of hepatitis E virus. Virus Res. 127, 216–228 (2007).

    Google Scholar 

  9. 9

    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).

    Google Scholar 

  10. 10

    Viswanathan, R. Epidemiology. Indian J. Med. Res. 45 (Suppl.), 1–29 (1957). This paper describes the first and largest outbreak of HEV infection, which led to many deaths.

    Google Scholar 

  11. 11

    Naik, S. R., Aggarwal, R., Salunke, P. N. & Mehrotra, N. N. A large waterborne viral hepatitis E epidemic in Kanpur, India. Bull. World Health Organ. 70, 597–604 (1992).

    Google Scholar 

  12. 12

    Khuroo, M. S. Chronic liver disease after non-A, non-B hepatitis. Lancet 2, 860–861 (1980).

    Google Scholar 

  13. 13

    Teshale, E. H. et al. Evidence of person-to-person transmission of hepatitis E virus during a large outbreak in Northern Uganda. Clin. Infect. Dis. 50, 1006–1010 (2010).

    Google Scholar 

  14. 14

    Thompson, K. et al. Investigation of hepatitis E outbreak among refugees — Upper Nile, South Sudan, 2012–2013. MMWR Morb. Mortal. Wkly Rep. 62, 581–586.

  15. 15

    Aggarwal, R. & Naik, S. R. Hepatitis E: intrafamilial transmission versus waterborne spread. J. Hepatol. 21, 718–723 (1994).

    Google Scholar 

  16. 16

    Somani, S. K., Aggarwal, R., Naik, S. R., Srivastava, S. & Naik, S. A serological study of intrafamilial spread from patients with sporadic hepatitis E virus infection. J. Viral Hepat. 10, 446–449 (2003).

    Google Scholar 

  17. 17

    Aggarwal, R. Hepatitis E virus and person-to-person transmission. Clin. Infect. Dis. 51, 477–478 (2010).

    Google Scholar 

  18. 18

    Nishiura, H. Household data from the Ugandan hepatitis E virus outbreak indicate the dominance of community infection. Clin. Infect. Dis. 51, 117–118 (2010).

    Google Scholar 

  19. 19

    Khuroo, M. S., Kamili, S. & Jameel, S. Vertical transmission of hepatitis E virus. Lancet 345, 1025–1026 (1995).

    Google Scholar 

  20. 20

    Khuroo, M. S., Kamili, S. & Khuroo, M. S. Clinical course and duration of viremia in vertically transmitted hepatitis E virus (HEV) infection in babies born to HEV-infected mothers. J. Viral Hepat. 16, 519–523 (2009).

    Google Scholar 

  21. 21

    Khuroo, M. S., Kamili, S. & Yattoo, G. N. Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area. J. Gastroenterol. Hepatol. 19, 778–784 (2004).

    Google Scholar 

  22. 22

    Arankalle, V. A. & Chobe, L. P. Retrospective analysis of blood transfusion recipients: evidence for post-transfusion hepatitis E. Vox Sang. 79, 72–74 (2000).

    Google Scholar 

  23. 23

    Viswanathan, R. Infectious hepatitis in Delhi (1955–1956): a critical study — epidemiology. Indian J. Med. Res. 45 (Suppl. 12), 1–29 (1957).

    Google Scholar 

  24. 24

    World Health Organization. Waterborne outbreaks of hepatitis E: recognition, investigation and control. Technical report (WHO, 2014)

  25. 25

    Fix, A. D. et al. Prevalence of antibodies to hepatitis E in two rural Egyptian communities. Am. J. Trop. Med. Hyg. 62, 519–523 (2000).

    Google Scholar 

  26. 26

    Stoszek, S. K. et al. High prevalence of hepatitis E antibodies in pregnant Egyptian women. Trans. R. Soc. Trop. Med. Hyg. 100, 95–101 (2006).

    Google Scholar 

  27. 27

    Dai, X. et al. Hepatitis E virus genotype 4, Nanjing, China, 2001–2011. Emerg. Infect. Dis. 19, 1528–1530 (2013).

    Google Scholar 

  28. 28

    Inagaki, Y. et al. A nationwide survey of hepatitis E virus infection and chronic hepatitis E in liver transplant recipients in Japan. EBioMedicine 2, 1607–1612 (2015).

    Google Scholar 

  29. 29

    Minagi, T. et al. Hepatitis E virus in donor plasma collected in Japan. Vox Sang. 111, 242–246 (2016).

    Google Scholar 

  30. 30

    Pischke, S. et al. High clinical manifestation rate in an imported outbreak of hepatitis E genotype 1 infection in a German group of travellers returning from India. Ann. Hepatol. 16, 57–62 (2017).

    Google Scholar 

  31. 31

    Van Cauteren, D. et al. Estimated annual numbers of foodborne pathogen-associated illnesses, hospitalizations, and deaths, France, 2008–2013. Emerg. Infect. Dis. 23, 1486–1492 (2017). This recent and well-documented study shows that hepatitis E has become the leading cause of viral hepatitis in France and is responsible for a large number of hospitalizations and death.

    Google Scholar 

  32. 32

    Hewitt, P. E. et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet 384, 1766–1773 (2014). This paper is one of the first studies that clearly assessed the prevalence of HEV RNA among blood donors; it described blood component-induced HEV transmission that leads to chronic hepatitis in immunosuppressed patients.

    Google Scholar 

  33. 33

    Faber, M. S. et al. Hepatitis E virus seroprevalence among adults Germany. Emerg. Infect. Dis. 18, 1654–1657 (2012).

    Google Scholar 

  34. 34

    Aspinall, E. J. et al. Hepatitis E virus infection in Europe: surveillance and descriptive epidemiology of confirmed cases 2005 to 2015. Eurosurveillance 22 29 (2017).

  35. 35

    Doting, M. H. E., Weel, J., Niesters, H. G. M., Riezebos-Brilman, A. & Brandenburg, A. The added value of hepatitis E diagnostics in determining causes of hepatitis in routine diagnostic settings in the Netherlands. Clin. Microbiol. Infect. 23, 667–671 (2017).

    Google Scholar 

  36. 36

    Wenzel, J. J. et al. Decline in hepatitis E virus antibody prevalence in southeastern Germany, 1996–2011. Hepatology 60, 1180–1186 (2014).

    Google Scholar 

  37. 37

    Kuniholm, M. H. et al. Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988–1994. J. Infect. Dis. 200, 48–56 (2009).

    Google Scholar 

  38. 38

    Ditah, I. et al. Current epidemiology of hepatitis E virus infection in the United States: low seroprevalence in the National Health and Nutrition Evaluation Survey. Hepatology 60, 815–822 (2014).

    Google Scholar 

  39. 39

    Roth, N. J. et al. Low hepatitis E virus RNA prevalence in a large-scale survey of United States source plasma donors. Transfusionhttp://dx.doi.org/10.1111/trf.14285 (2017).

  40. 40

    Nelson, K. E., Kmush, B. & Labrique, A. B. The epidemiology of hepatitis E virus infections in developed countries and among immunocompromised patients. Expert Rev. Anti Infect. Ther. 9, 1133–1148 (2011).

    Google Scholar 

  41. 41

    Kuniholm, M. H. et al. Acute and chronic hepatitis E virus infection in human immunodeficiency virus-infected U.S. women. Hepatology 63, 712–720 (2016).

    Google Scholar 

  42. 42

    Chapuy-Regaud, S. et al. Characterization of the lipid envelope of exosome encapsulated HEV particles protected from the immune response. Biochimie 141, 70–79 (2017).

  43. 43

    Koonin, E. V. et al. Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: delineation of an additional group of positive-strand RNA plant and animal viruses. Proc. Natl Acad. Sci. USA 89, 8259–8263 (1992).

    Google Scholar 

  44. 44

    Lhomme, S. et al. Influence of polyproline region and macro domain genetic heterogeneity on HEV persistence in immunocompromised patients. J. Infect. Dis. 209, 300–303 (2014).

    Google Scholar 

  45. 45

    Shukla, P. et al. Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant. Proc. Natl Acad. Sci. USA 108, 2438–2443 (2011).

    Google Scholar 

  46. 46

    Johne, R. et al. An ORF1-rearranged hepatitis E virus derived from a chronically infected patient efficiently replicates in cell culture. J. Viral Hepat. 21, 447–456 (2014).

    Google Scholar 

  47. 47

    Nair, V. P. et al. Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis E virus. PLoS Pathog. 12, e1005521 (2016).

    Google Scholar 

  48. 48

    Zafrullah, M., Ozdener, M. H., Kumar, R., Panda, S. K. & Jameel, S. Mutational analysis of glycosylation, membrane translocation, and cell surface expression of the hepatitis E virus ORF2 protein. J. Virol. 73, 4074–4082 (1999).

    Google Scholar 

  49. 49

    Guu, T. S. et al. Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding. Proc. Natl Acad. Sci. USA 106, 12992–12997 (2009).

    Google Scholar 

  50. 50

    Yamashita, T. et al. Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure. Proc. Natl Acad. Sci. USA 106, 12986–12991 (2009).

    Google Scholar 

  51. 51

    Xing, L. et al. Structure of hepatitis E virion-sized particle reveals an RNA-dependent viral assembly pathway. J. Biol. Chem. 285, 33175–33183 (2010).

    Google Scholar 

  52. 52

    Tang, X. et al. Structural basis for the neutralization and genotype specificity of hepatitis E virus. Proc. Natl Acad. Sci. USA 108, 10266–10271 (2011).

    Google Scholar 

  53. 53

    Xing, L. et al. Spatial configuration of hepatitis E virus antigenic domain. J. Virol. 85, 1117–1124 (2011).

    Google Scholar 

  54. 54

    Lhomme, S. et al. HEV quasispecies and the outcome of acute hepatitis E in solid-organ transplant patients. J. Virol. 86, 100006–100014 (2012).

    Google Scholar 

  55. 55

    Tyagi, S., Korkaya, H., Zafrullah, M., Jameel, S. & Lal, S. K. The phosphorylated form of the ORF3 protein of hepatitis E virus interacts with its non-glycosylated form of the major capsid protein, ORF2. J. Biol. Chem. 277, 22759–22767 (2002).

    Google Scholar 

  56. 56

    Emerson, S. U. et al. Release of genotype 1 hepatitis E virus from cultured hepatoma and polarized intestinal cells depends on open reading frame 3 protein and requires an intact PXXP motif. J. Virol. 84, 9059–9069 (2010).

    Google Scholar 

  57. 57

    Nagashima, S. et al. A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for virion release from infected cells. J. Gen. Virol. 92, 269–278 (2011).

    Google Scholar 

  58. 58

    Purdy, M. A. & Khudyakov, Y. E. Evolutionary history and population dynamics of hepatitis E virus. PLoS ONE 5, e14376 (2010).

    Google Scholar 

  59. 59

    Brayne, A. B., Dearlove, B. L., Lester, J. S., Kosakovsky Pond, S. L. & Frost, S. D. Genotype-specific evolution of Hepatitis E Virus. J. Virol. 91, e02241-16 (2017).

    Google Scholar 

  60. 60

    Purcell, R. H. & Emerson, S. U. Hepatitis E: an emerging awareness of an old disease. J. Hepatol. 48, 494–503 (2008).

    Google Scholar 

  61. 61

    Purcell, R. H. et al. Pathobiology of hepatitis E: lessons learned from primate models. Emerg. Microbes Infect. 2, e9 (2013).

    Google Scholar 

  62. 62

    Meng, X. J. et al. Experimental infection of pigs with the newly identified swine hepatitis E virus (swine HEV), but not with human strains of HEV. Arch. Virol. 143, 1405–1415 (1998).

    Google Scholar 

  63. 63

    La Rosa, G., Pourshaban, M., Iaconelli, M., Vennarucci, V. S. & Muscillo, M. Molecular detection of hepatitis E virus in sewage samples. Appl. Environ. Microbiol. 76, 5870–5873 (2010).

    Google Scholar 

  64. 64

    Mansuy, J. M. et al. A nationwide survey of hepatitis E viral infection in French blood donors. Hepatology 63, 1145–1154 (2016). This paper shows that HEV is endemic among blood donors in France and describes risk factors for anti-HEV IgG and anti-HEV IgM prevalence.

    Google Scholar 

  65. 65

    Doceul, V., Bagdassarian, E., Demange, A. & Pavio, N. Zoonotic hepatitis E virus: classification, animal reservoirs and transmission routes. Viruses 8, 270 (2016).

    Google Scholar 

  66. 66

    Schlosser, J. et al. Natural and experimental hepatitis E virus genotype 3-infection in European wild boar is transmissible to domestic pigs. Vet. Res. 45, 121 (2014).

    Google Scholar 

  67. 67

    Izopet, J. et al. Hepatitis E virus strains in rabbits and evidence of a closely related strain in humans, france. Emerg. Infect. Dis. 18, 1274–1281 (2012).

    Google Scholar 

  68. 68

    Yan, B. et al. Hepatitis E Virus in yellow cattle, Shandong, Eastern China. Emerg. Infect. Dis. 22, 2211–2212 (2016).

    Google Scholar 

  69. 69

    Casas, M. et al. Longitudinal study of hepatitis E virus infection in Spanish farrow-to-finish swine herds. Vet. Microbiol. 148, 27–34 (2011).

    Google Scholar 

  70. 70

    Salines, M., Andraud, M. & Rose, N. From the epidemiology of hepatitis E virus (HEV) within the swine reservoir to public health risk mitigation strategies: a comprehensive review. Vet. Res. 48, 31 (2017).

    Google Scholar 

  71. 71

    Colson, P. et al. Pig liver sausage as a source of hepatitis E virus transmission to humans. J. Infect. Dis. 202, 825–834 (2010).

    Google Scholar 

  72. 72

    Renou, C., Roque-Afonso, A. M. & Pavio, N. Foodborne transmission of hepatitis E virus from raw pork liver sausage, France. Emerg. Infect. Dis. 20, 1945–1947 (2014).

    Google Scholar 

  73. 73

    Riveiro-Barciela, M. et al. Phylogenetic demonstration of hepatitis E infection transmitted by pork meat ingestion. J. Clin. Gastroenterol. 49, 165–168 (2015).

    Google Scholar 

  74. 74

    Huang, F. et al. Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis. Hepatology 64, 350–359 (2016).

    Google Scholar 

  75. 75

    Lange, H. et al. Hepatitis E in Norway: seroprevalence in humans and swine. Epidemiol. Infect. 145, 181–186 (2017).

    Google Scholar 

  76. 76

    Colson, P., Kaba, M., Bernit, E., Motte, A. & Tamalet, C. Hepatitis E associated with surgical training on pigs. Lancet 370, 935 (2007).

    Google Scholar 

  77. 77

    Perez-Gracia, M. T. et al. Autochthonous hepatitis E infection in a slaughterhouse worker. Am. J. Trop. Med. Hyg. 77, 893–896 (2007).

    Google Scholar 

  78. 78

    Renou, C. et al. Possible zoonotic transmission of hepatitis E from pet pig to its owner. Emerg. Infect. Dis. 13, 1094–1096 (2007).

    Google Scholar 

  79. 79

    Chaussade, H. et al. Hepatitis E virus seroprevalence and risk factors for individuals in working contact with animals. J. Clin. Virol. 58, 504–508 (2013).

    Google Scholar 

  80. 80

    Di Bartolo, I. et al. Hepatitis E virus in pork production chain in Czech Republic, Italy, and Spain, 2010. Emerg. Infect. Dis. 18, 1282–1289 (2012).

    Google Scholar 

  81. 81

    Nantel-Fortier, N. et al. Detection and phylogenetic analysis of the hepatitis E virus in a Canadian swine production network. Food Environ. Virol. 8, 296–304 (2016).

    Google Scholar 

  82. 82

    van Gageldonk-Lafeber, A. B. et al. Hepatitis E virus seroprevalence among the general population in a livestock-dense area in the Netherlands: a cross-sectional population-based serological survey. BMC Infect. Dis. 17, 21 (2017).

    Google Scholar 

  83. 83

    Cossaboom, C. M., Cordoba, L., Cao, D., Ni, Y. Y. & Meng, X. J. Complete genome sequence of hepatitis E virus from rabbits in the United States. J. Virol. 86, 13124–13125 (2012).

    Google Scholar 

  84. 84

    Lhomme, S. et al. Wildlife reservoir for hepatitis E virus, Southwestern France. Emerg. Infect. Dis. 21, 1224–1226 (2015).

    Google Scholar 

  85. 85

    Abravanel, F. et al. Rabbit hepatitis E virus infections in humans, France. Emerg. Infect. Dis. 23, 1191–1193 (2017).

    Google Scholar 

  86. 86

    Liu, P. et al. Transmission of hepatitis E virus from rabbits to cynomolgus macaques. Emerg. Infect. Dis. 19, 559–565 (2013).

    Google Scholar 

  87. 87

    Cossaboom, C. M. et al. Cross-species infection of pigs with a novel rabbit, but not rat, strain of hepatitis E virus isolated in the United States. J. Gen. Virol. 93, 1687–1695 (2012).

    Google Scholar 

  88. 88

    Lee, G. H. et al. Chronic infection with camelid hepatitis E virus in a liver transplant recipient who regularly consumes camel meat and milk. Gastroenterology 150, 355–357.e3 (2016).

    Google Scholar 

  89. 89

    Li, T. C. et al. Generation of hepatitis E virus-like particles of two new genotypes G5 and G6 and comparison of antigenic properties with those of known genotypes. Vet. Microbiol. 178, 150–157 (2015).

    Google Scholar 

  90. 90

    Grodzki, M. et al. Bioaccumulation efficiency, tissue distribution, and environmental occurrence of hepatitis E virus in bivalve shellfish from France. Appl. Environ. Microbiol. 80, 4269–4276 (2014).

    Google Scholar 

  91. 91

    Crossan, C. et al. Hepatitis E virus genotype 3 in shellfish, United Kingdom. Emerg. Infect. Dis. 18, 2085–2087 (2012).

    Google Scholar 

  92. 92

    Said, B. et al. Hepatitis E outbreak on cruise ship. Emerg. Infect. Dis. 15, 1738–1744 (2009).

    Google Scholar 

  93. 93

    Tedder, R. S. et al. Hepatitis E risks: pigs or blood-that is the question. Transfusion 57, 267–272 (2017).

    Google Scholar 

  94. 94

    Zhang, L. et al. Prevalence of hepatitis E virus infection among blood donors in mainland China: a meta-analysis. Transfusion 57, 248–257 (2017).

    Google Scholar 

  95. 95

    Satake, M. et al. Unique clinical courses of transfusion-transmitted hepatitis E in patients with immunosuppression. Transfusion 57, 280–288 (2017).

    Google Scholar 

  96. 96

    Baylis, S. A. et al. Unusual serological response to hepatitis E virus in plasma donors consistent with re-infection. Vox Sang. 109, 406–409 (2015).

    Google Scholar 

  97. 97

    Suneetha, P. V. et al. Hepatitis E virus (HEV)-specific T-cell responses are associated with control of HEV infection. Hepatology 55, 695–708 (2012).

    Google Scholar 

  98. 98

    Abravanel, F. et al. Conventional and innate lymphocytes response at the acute phase of HEV infection in transplanted patients. J. Infect. 72, 723–730 (2016).

    Google Scholar 

  99. 99

    Cao, D. et al. Pig model mimicking chronic hepatitis E virus infection in immunocompromised patients to assess immune correlates during chronicity. Proc. Natl Acad. Sci. USA 114, 6914–6923 (2017).

    Google Scholar 

  100. 100

    Bouwknegt, M. et al. The course of hepatitis E virus infection in pigs after contact-infection and intravenous inoculation. BMC Vet. Res. 5, 7 (2009).

    Google Scholar 

  101. 101

    Aggarwal, R., Kini, D., Sofat, S., Naik, S. R. & Krawczynski, K. Duration of viraemia and faecal viral excretion in acute hepatitis E. Lancet 356, 1081–1082 (2000).

    Google Scholar 

  102. 102

    Williams, T. P. et al. Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model. J. Clin. Microbiol. 39, 3040–3046 (2001).

    Google Scholar 

  103. 103

    Geng, Y. et al. Detection and assessment of infectivity of hepatitis E virus in urine. J. Hepatol. 64, 37–43 (2016).

    Google Scholar 

  104. 104

    Drave, S. A. et al. Extra-hepatic replication and infection of hepatitis E virus in neuronal-derived cells. J. Viral Hepat. 23, 512–521 (2016).

    Google Scholar 

  105. 105

    Bose, P. D. et al. Evidence of extrahepatic replication of hepatitis E virus in human placenta. J. Gen. Virol. 95, 1266–1271 (2014).

    Google Scholar 

  106. 106

    Pischke, S. et al. Blood-borne Hepatitis E Virus Transmission: A Relevant Risk for Immunosuppressed Patients. Clin. Infect. Dis. 63, 569–570 (2016).

    Google Scholar 

  107. 107

    Zhang, J. et al. Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity. Clin. Microbiol. Infect. 20, O397–O405 (2014).

    Google Scholar 

  108. 108

    Aggarwal, R. Diagnosis of hepatitis E. Nat. Rev. Gastroenterol. Hepatol. 10, 24–33 (2013).

    Google Scholar 

  109. 109

    Wen, G. P. et al. A valuable antigen detection method for diagnosis of acute hepatitis E. J. Clin. Microbiol. 53, 782–788 (2015).

    Google Scholar 

  110. 110

    Huang, S. et al. Profile of acute infectious markers in sporadic hepatitis E. PLoS ONE 5, e13560 (2010).

    Google Scholar 

  111. 111

    Norder, H. et al. Diagnostic performance of five assays for anti-hepatitis E virus IgG and IgM in a large cohort study. J. Clin. Microbiol. 54, 549–555 (2016).

    Google Scholar 

  112. 112

    Abravanel, F. et al. Performance of anti-HEV assays for diagnosis acute hepatitis E in immunocompromised patients. J. Clin. Virol. 58, 624–628 (2013).

    Google Scholar 

  113. 113

    Legrand-Abravanel, F. et al. Good performance of immunoglobulin M assays in diagnosing genotype 3 hepatitis E virus infections. Clin. Vaccine Immunol. 16, 772–774 (2009).

    Google Scholar 

  114. 114

    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). This study is the first to show discrepancies between HEV serological assays.

    Google Scholar 

  115. 115

    Abravanel, F. et al. Hepatitis E virus reinfections in solid-organ-transplant recipients can evolve into chronic infections. J. Infect. Dis. 209, 1900–1906 (2014).

    Google Scholar 

  116. 116

    Abravanel, F. et al. Performance of two commercial assays for detecting hepatitis E virus RNA in acute or chronic infections. J. Clin. Microbiol. 51, 1913–1916 (2013).

    Google Scholar 

  117. 117

    Abravanel, F. et al. Genotype 3 diversity and quantification of hepatitis E virus RNA. J. Clin. Microbiol. 50, 897–902 (2012).

    Google Scholar 

  118. 118

    Sauleda, S. et al. Seroprevalence of hepatitis E virus (HEV) and detection of HEV RNA with a transcription-mediated amplification assay in blood donors from Catalonia (Spain). Transfusion 55, 972–979 (2015).

    Google Scholar 

  119. 119

    Gou, H. et al. Rapid and sensitive detection of type II porcine reproductive and respiratory syndrome virus by reverse transcription loop-mediated isothermal amplification combined with a vertical flow visualization strip. J. Virol. Methods 209, 86–94 (2014).

    Google Scholar 

  120. 120

    Debing, Y. et al. Hepatitis E virus mutations associated with ribavirin treatment failure result in altered viral fitness and ribavirin sensitivity. J. Hepatol. 65, 499–508 (2016).

    Google Scholar 

  121. 121

    Lhomme, S. et al. Mutation in the hepatitis E virus polymerase and outcome of ribavirin therapy. Antimicrob. Agents Chemother. 60, 1608–1614 (2015).

    Google Scholar 

  122. 122

    Tremeaux, P. et al. Performance of an antigen assay for diagnosing acute hepatitis E virus genotype 3 infection. J. Clin. Virol. 79, 1–5 (2016).

    Google Scholar 

  123. 123

    Abravanel, F., Lhomme, S., Rostaing, L., Kamar, N. & Izopet, J. Protracted fecal shedding of HEV during ribavirin therapy predicts treatment relapse. Clin. Infect. Dis. 60, 96–99 (2015).

    Google Scholar 

  124. 124

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

    Google Scholar 

  125. 125

    Blasco-Perrin, H. et al. Hepatitis E virus in patients with decompensated chronic liver disease: a prospective UK/French study. Aliment. Pharmacol. Ther. 42, 574–581 (2015).

    Google Scholar 

  126. 126

    Kumar, A. & Saraswat, V. A. Hepatitis E and acute-on-chronic liver failure. J. Clin. Exp. Hepatol. 3, 225–230 (2013).

    Google Scholar 

  127. 127

    Shalimar, S. K. et al. Severity and outcome of acute-on-chronic liver failure is dependent on the etiology of acute hepatic insults: analysis of 368 patients. J. Clin. Gastroenterol. 51, 734–741 (2017).

    Google Scholar 

  128. 128

    Naik, A. et al. Lack of evidence of hepatitis E virus infection among renal transplant recipients in a disease-endemic area. J. Viral Hepat. 20, e138–e140 (2013).

    Google Scholar 

  129. 129

    Naidu, S. S. & Viswanathan, R. Infectious hepatitis in pregnancy during Delhi epidemic. Indian J. Med. Res. 45, 71–76 (1957).

    Google Scholar 

  130. 130

    Jilani, N. et al. Hepatitis E virus infection and fulminant hepatic failure during pregnancy. J. Gastroenterol. Hepatol. 22, 676–682 (2007).

    Google Scholar 

  131. 131

    Zhu, F. C. et al. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet 376, 895–902 (2010). This paper reports the results of a prospective randomized trial that assessed the efficacy and safety of the available vaccine against HEV.

    Google Scholar 

  132. 132

    Guillois, Y. et al. High proportion of asymptomatic infections in an outbreak of hepatitis E associated with a spit-roasted piglet, France, 2013. Clin. Infect. Dis. 62, 351–357 (2016).

    Google Scholar 

  133. 133

    Peron, J. M. et al. Fulminant liver failure from acute autochthonous hepatitis E in France: description of seven patients with acute hepatitis E and encephalopathy. J. Viral Hepat. 14, 298–303 (2007).

    Google Scholar 

  134. 134

    Manka, P. et al. Hepatitis E virus infection as a possible cause of acute liver failure in Europe. Clin. Gastroenterol. Hepatol. 13, 1836–1842 (2015).

    Google Scholar 

  135. 135

    Aherfi, S. et al. Liver transplantation for acute liver failure related to autochthonous genotype 3 hepatitis E virus infection. Clin. Res. Hepatol. Gastroenterol. 38, 24–31 (2014).

    Google Scholar 

  136. 136

    Haim-Boukobza, S. et al. Hepatitis E infection in patients with severe acute alcoholic hepatitis. Liver Int. 35, 870–875 (2015).

    Google Scholar 

  137. 137

    Anty, R. et al. First case report of an acute genotype 3 hepatitis E infected pregnant woman living in South-Eastern France. J. Clin. Virol. 54, 76–78 (2012).

    Google Scholar 

  138. 138

    Renou, C. et al. Prospective study of Hepatitis E Virus infection among pregnant women in France. Virol. J. 11, 68 (2014).

    Google Scholar 

  139. 139

    Kamar, N. et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N. Engl. J. Med. 358, 811–817 (2008). This is the first series of chronic HEV infections reported in immunosuppressed patients, that is, in patients who received SOT.

    Google Scholar 

  140. 140

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

    Google Scholar 

  141. 141

    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).

    Google Scholar 

  142. 142

    Hoerning, A. et al. Prevalence of hepatitis E virus infection in pediatric solid organ transplant recipients — a single-center experience. Pediatr. Transplant. 16, 742–747 (2012).

    Google Scholar 

  143. 143

    Koenecke, C. et al. Hepatitis E virus infection in a hematopoietic stem cell donor. Bone Marrow Transplant. 49, 159–160 (2014).

    Google Scholar 

  144. 144

    Tavitian, S. et al. Hepatitis E virus excretion can be prolonged in patients with hematological malignancies. J. Clin. Virol. 49, 141–144 (2010).

    Google Scholar 

  145. 145

    Ollier, L. et al. Chronic hepatitis after hepatitis E virus infection in a patient with non-Hodgkin lymphoma taking rituximab. Ann. Intern. Med. 150, 430–431 (2009).

    Google Scholar 

  146. 146

    Bauer, H. et al. Outcome of hepatitis E virus infection in patients with inflammatory arthritides treated with immunosuppressants: a French retrospective multicenter study. Medicine 94, e675 (2015).

    Google Scholar 

  147. 147

    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).

    Google Scholar 

  148. 148

    Kamar, N., Rostaing, L., Legrand-Abravanel, F. & Izopet, J. How should hepatitis E virus infection be defined in organ-transplant recipients? Am. J. Transplant. 13, 1935–1936 (2013).

    Google Scholar 

  149. 149

    Geng, Y. et al. Persistent hepatitis e virus genotype 4 infection in a child with acute lymphoblastic leukemia. Hepat. Mon. 14, e15618 (2014).

    Google Scholar 

  150. 150

    Kamar, N. et al. Influence of immunosuppressive therapy on the natural history of genotype 3 hepatitis-E virus infection after organ transplantation. Transplantation 89, 353–360 (2010).

    Google Scholar 

  151. 151

    Kamar, N. et al. Hepatitis E virus-related cirrhosis in kidney- and kidney-pancreas-transplant recipients. Am. J. Transplant. 8, 1744–1748 (2008).

    Google Scholar 

  152. 152

    Kamar, N., Izopet, J. & Rostaing, L. No reactivation of hepatitis E virus after kidney retransplantation. Am. J. Transplant. 12, 507–508 (2012).

    Google Scholar 

  153. 153

    Dalton, H. R. et al. Hepatitis E virus and neurological injury. Nat. Rev. Neurol. 12, 77–85 (2016). In this Review, the authors summarize all available data regarding HEV-associated neurological manifestations.

    Google Scholar 

  154. 154

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

    Google Scholar 

  155. 155

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

    Google Scholar 

  156. 156

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

    Google Scholar 

  157. 157

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

    Google Scholar 

  158. 158

    Fukae, J. et al. Guillain-Barre and Miller Fisher syndromes in patients with anti-hepatitis E virus antibody: a hospital-based survey in Japan. Neurol. Sci. 37, 1849–1851 (2016).

    Google Scholar 

  159. 159

    Stevens, O., Claeys, K. G., Poesen, K., Saegeman, V. & Van Damme, P. Diagnostic challenges and clinical characteristics of hepatitis E virus-associated Guillain-Barre syndrome. JAMA Neurol. 74, 26–33 (2017).

    Google Scholar 

  160. 160

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

    Google Scholar 

  161. 161

    Dalton, H. R. et al. Hepatitis E infection and acute non-traumatic neurological injury: a prospective pilot multicenter study. J. Hepatol. http://dx.doi.org/10.1016/j.jhep.2017.07.010 (2017).

  162. 162

    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).

    Google Scholar 

  163. 163

    Silva, M. et al. Hepatitis E virus infection as a direct cause of neuralgic amyotrophy. Muscle Nerve 54, 325–327 (2016).

    Google Scholar 

  164. 164

    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).

    Google Scholar 

  165. 165

    Shi, R. et al. Evidence of Hepatitis E virus breaking through the blood-brain barrier and replicating in the central nervous system. J. Viral Hepat. 23, 930–939 (2016).

    Google Scholar 

  166. 166

    Zhou, X. et al. Hepatitis E virus infects neurons and brains. J. Infect. Dis. 215, 1197–1206 (2017).

    Google Scholar 

  167. 167

    Kamar, N. et al. Acute hepatitis and renal function impairment related to infection by hepatitis E virus in a renal allograft recipient. Am. J. Kidney Dis. 45, 193–196 (2005).

    Google Scholar 

  168. 168

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

    Google Scholar 

  169. 169

    Ali, G., Kumar, M., Bali, S. & Wadhwa, W. Heptitis E associated immune thrombocytopenia and membranous glomerulonephritis. Indian J. Nephrol. 11, 70–72 (2001).

    Google Scholar 

  170. 170

    Taton, B. et al. Hepatitis E virus infection as a new probable cause of de novo membranous nephropathy after kidney transplantation. Transpl. Infect. Dis. 15, E211–E215 (2013).

    Google Scholar 

  171. 171

    Guinault, D. et al. Hepatitis E virus-induced cryglobulinemic glomerulonephritis in a non-immunocompromised person. Am. J. Kidney Dis. 67, 660–663 (2016).

    Google Scholar 

  172. 172

    Del Bello, A. et al. Successful treatment of hepatitis E virus-associated cryoglobulinemic membranoproliferative glomerulonephritis with ribavirin. Transpl. Infect. Dis. 17, 279–283 (2015).

    Google Scholar 

  173. 173

    de Vos, A. S., Janssen, M. P., Zaaijer, H. L. & Hogema, B. M. Cost-effectiveness of the screening of blood donations for hepatitis E virus in the Netherlands. Transfusion 57, 258–266 (2017).

    Google Scholar 

  174. 174

    Haque, F. et al. An outbreak of hepatitis E in an urban area of Bangladesh. J. Viral Hepat. 22, 948–956 (2015).

    Google Scholar 

  175. 175

    Feagins, A. R., Opriessnig, T., Guenette, D. K., Halbur, P. G. & Meng, X. J. Inactivation of infectious hepatitis E virus present in commercial pig livers sold in local grocery stores in the United States. Int. J. Food Microbiol. 123, 32–37 (2008).

    Google Scholar 

  176. 176

    Barnaud, E., Rogee, S., Garry, P., Rose, N. & Pavio, N. Thermal inactivation of infectious hepatitis E virus in experimentally contaminated food. Appl. Environ. Microbiol. 78, 5153–5159 (2012).

    Google Scholar 

  177. 177

    Johne, R., Trojnar, E., Filter, M. & Hofmann, J. Thermal stability of hepatitis E virus as estimated by a cell culture method. Appl. Environ. Microbiol. 82, 4225–4231 (2016).

    Google Scholar 

  178. 178

    Emerson, S. U., Arankalle, V. A. & Purcell, R. H. Thermal stability of hepatitis E virus. J. Infect. Dis. 192, 930–933 (2005).

    Google Scholar 

  179. 179

    Schielke, A. et al. Hepatitis E virus antibody prevalence in hunters from a district in Central Germany, 2013: a cross-sectional study providing evidence for the benefit of protective gloves during disembowelling of wild boars. BMC Infect. Dis. 15, 440 (2015).

    Google Scholar 

  180. 180

    Zhang, J. et al. Long-term efficacy of a hepatitis E vaccine. N. Engl. J. Med. 372, 914–922 (2015). This is the first paper to show the long-term efficacy of the anti-HEV vaccine.

    Google Scholar 

  181. 181

    Su, Y. Y. et al. Persistence of antibodies acquired by natural hepatitis E virus infection and effects of vaccination. Clin. Microbiol. Infect. 23, 336.e1–336.e4 (2017).

    Google Scholar 

  182. 182

    World Health Organization. Global Advisory Committee on Vaccine Safety, 11–12 June 2014. Wkly Epidemiol. Rec. 89, 325–336 (2014).

    Google Scholar 

  183. 183

    Tillmann, H., Patel, K. & McHutchison, J. Hepatitis B virus viral load and treatment decision. Hepatology 49, 699 (2009).

  184. 184

    Wiegand, J. et al. Treatment of severe, nonfulminant acute hepatitis B with lamivudine versus placebo: a prospective randomized double-blinded multicentre trial. J. Viral Hepat. 21, 744–750 (2014).

    Google Scholar 

  185. 185

    Deterding, K. et al. Ledipasvir plus sofosbuvir fixed-dose combination for 6 weeks in patients with acute hepatitis C virus genotype 1 monoinfection (HepNet Acute HCV IV): an open-label, single-arm, phase 2 study. Lancet Infect. Dis. 17, 215–222 (2017).

    Google Scholar 

  186. 186

    Peron, J. M. et al. Treatment of autochthonous acute hepatitis E with short-term ribavirin: a multicenter retrospective study. Liver Int. 36, 328–333 (2016).

    Google Scholar 

  187. 187

    Gerolami, R. et al. Treatment of severe acute hepatitis E by ribavirin. J. Clin. Virol. 52, 60–62 (2011).

    Google Scholar 

  188. 188

    Pischke, S. et al. Ribavirin treatment of acute and chronic hepatitis E: a single-centre experience. Liver Int. 33, 722–726 (2013).

    Google Scholar 

  189. 189

    Goyal, R., Kumar, A., Panda, S. K., Paul, S. B. & Acharya, S. K. Ribavirin therapy for hepatitis E virus-induced acute on chronic liver failure: a preliminary report. Antivir. Ther. 17, 1091–1096 (2012).

    Google Scholar 

  190. 190

    Kamar, N. et al. Ribavirin for chronic hepatitis E virus infection in transplant recipients. N. Engl. J. Med. 370, 1111–1120 (2014). This paper describes the largest series of patients who received SOT with chronic hepatitis who were given ribavirin therapy. A sustained virological response was observed in the majority of patients.

    Google Scholar 

  191. 191

    Kamar, N. et al. An early viral response predicts the virological response to ribavirin in hepatitis E virus organ transplant patients. Transplantation 99, 2124–2131 (2015).

    Google Scholar 

  192. 192

    Wang, Y. et al. Calcineurin inhibitors stimulate and mycophenolic acid inhibits replication of hepatitis E virus. Gastroenterology 146, 1775–1783 (2014).

    Google Scholar 

  193. 193

    Debing, Y. et al. A mutation in the hepatitis E virus RNA polymerase promotes its replication and associates with ribavirin treatment failure in organ transplant recipients. Gastroenterology 147, 1008–1011.e7 (2014).

  194. 194

    Todt, D. et al. Antiviral activities of different interferon types and subtypes against hepatitis E virus replication. Antimicrob. Agents Chemother. 60, 2132–2139 (2016).

    Google Scholar 

  195. 195

    Ikram, A. et al. Genotype-specific acquisition, evolution and adaptation of characteristic mutations in hepatitis E virus. Virulencehttp://dx.doi.org/10.1080/21505594.2017.1358349 (2017).

  196. 196

    Kamar, N. et al. Pegylated interferon-α for treating chronic hepatitis E virus infection after liver transplantation. Clin. Infect. Dis. 50, e30–e33 (2010).

    Google Scholar 

  197. 197

    Haagsma, E. B., Riezebos-Brilman, A., van den Berg, A. P., Porte, R. J. & Niesters, H. G. Treatment of chronic hepatitis E in liver transplant recipients with pegylated interferon alpha-2b. Liver Transpl. 16, 474–477 (2010).

    Google Scholar 

  198. 198

    Kamar, N. et al. Three-month pegylated interferon-alpha-2a therapy for chronic hepatitis E virus infection in a haemodialysis patient. Nephrol. Dial Transplant. 25, 2792–2795 (2010).

    Google Scholar 

  199. 199

    Rostaing, L. et al. Treatment of chronic hepatitis C with recombinant interferon alpha in kidney transplant recipients. Transplantation 59, 1426–1431 (1995).

    Google Scholar 

  200. 200

    Mallet, V. et al. Brief communication: case reports of ribavirin treatment for chronic hepatitis E. Ann. Intern. Med. 153, 85–89 (2010).

    Google Scholar 

  201. 201

    Kamar, N. et al. Ribavirin therapy inhibits viral replication in patients with chronic hepatitis E virus infection. Gastroenterology 139, 1612–1618 (2010).

    Google Scholar 

  202. 202

    Alric, L., Bonnet, D., Laurent, G., Kamar, N. & Izopet, J. Chronic hepatitis E virus infection: successful virologic response to pegylated interferon-α therapy. Ann. Intern. Med. 153, 135–136 (2010).

    Google Scholar 

  203. 203

    Alric, L., Bonnet, D., Beynes-Rauzy, O., Izopet, J. & Kamar, N. Definitive clearance of a chronic hepatitis E virus infection with ribavirin treatment. Am. J. Gastroenterol. 106, 1562–1563 (2011).

    Google Scholar 

  204. 204

    Tavitian, S. et al. Ribavirin for chronic hepatitis prevention among patients with hematologic malignancies. Emerg. Infect. Dis. 21, 1466–1469 (2015).

    Google Scholar 

  205. 205

    Neukam, K. et al. Chronic hepatitis E in HIV patients: rapid progression to cirrhosis and response to oral ribavirin. Clin. Infect. Dis. 57, 465–468 (2013).

    Google Scholar 

  206. 206

    Hajji, H., Gerolami, R., Solas, C., Moreau, J. & Colson, P. Chronic hepatitis E resolution in a human immunodeficiency virus (HIV)-infected patient treated with ribavirin. Int. J. Antimicrob. Agents 46, 595–597 (2013).

    Google Scholar 

  207. 207

    Labrique, A. B. et al. Epidemiology and risk factors of incident hepatitis E virus infections in rural Bangladesh. Am. J. Epidemiol. 172, 952–961 (2010).

    Google Scholar 

  208. 208

    Krain, L. J., Nelson, K. E. & Labrique, A. B. Host immune status and response to hepatitis E virus infection. Clin. Microbiol. Rev. 27, 139–165 (2014).

    Google Scholar 

  209. 209

    Zhou, X. et al. Rapamycin and everolimus facilitate hepatitis E virus replication: revealing a basal defense mechanism of PI3K-PKB-mTOR pathway. J. Hepatol. 61, 746–754 (2014).

    Google Scholar 

  210. 210

    Pischke, S. et al. Chronic hepatitis E in heart transplant recipients. Am. J. Transplant. 12, 3128–3133 (2012).

    Google Scholar 

  211. 211

    Dao Thi, V. L. et al. Sofosbuvir inhibits hepatitis E virus replication in vitro and results in an additive effect when combined with ribavirin. Gastroenterology 150, 82–85.e4 (2016).

    Google Scholar 

  212. 212

    Wang, W. et al. Distinct antiviral potency of sofosbuvir against hepatitis C and E viruses. Gastroenterology 151, 1251–1253 (2016).

    Google Scholar 

  213. 213

    van der Valk, M., Zaaijer, H. L., Kater, A. P. & Schinkel, J. Sofosbuvir shows antiviral activity in a patient with chronic hepatitis E virus infection. J. Hepatol. 66, 242–243 (2017).

    Google Scholar 

  214. 214

    Kamar, N., Wang, W., Dalton, H. R. & Pan, Q. Direct-acting antiviral therapy for hepatitis E virus? Lancet Gastroenterol. Hepatol. 2, 154–155 (2017).

    Google Scholar 

  215. 215

    Donnelly, M. C. et al. Review article: hepatitis E—a concise review of virology, epidemiology, clinical presentation and therapy. Aliment. Pharmacol. Ther. 46, 126–141 (2017).

    Google Scholar 

  216. 216

    Shrestha, A. C. et al. Hepatitis E virus RNA in Australian blood donations. Transfusion 56, 3086–3093 (2016).

    Google Scholar 

  217. 217

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

    Google Scholar 

  218. 218

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

    Google Scholar 

  219. 219

    Harritshoj, L. H. et al. Low transfusion transmission of hepatitis E among 25,637 single-donation, nucleic acid-tested blood donors. Transfusion 56, 2225–2232 (2016).

    Google Scholar 

  220. 220

    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).

    Google Scholar 

  221. 221

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

    Google Scholar 

  222. 222

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

    Google Scholar 

  223. 223

    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).

    Google Scholar 

  224. 224

    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).

    Google Scholar 

  225. 225

    O’Riordan, J. et al. Hepatitis E virus infection in the Irish blood donor population. Transfusion 56, 2868–2876 (2016).

    Google Scholar 

  226. 226

    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).

    Google Scholar 

  227. 227

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

    Google Scholar 

  228. 228

    Zaaijer, H. L. No artifact, hepatitis E is emerging. Hepatology 62, 654 (2015).

    Google Scholar 

  229. 229

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

    Google Scholar 

  230. 230

    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).

    Google Scholar 

  231. 231

    Stramer, S. L. et al. Hepatitis E virus: seroprevalence and frequency of viral RNA detection among US blood donors. Transfusion 56, 481–488 (2015).

    Google Scholar 

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Introduction (N.K. and H.R.D.); Epidemiology (R.A., H.W. and A.L.); Mechanisms/pathophysiology (N.P. and J.I.); Diagnosis, screening and prevention (J.I., H.R.D., A.L., R.A., H.W. and N.K.); Management (N.K. and H.W.); Quality of life (A.L.); Outlook (N.K. and H.R.D.); Overview of the Primer (N.K. and H.R.D.).

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Correspondence to Nassim Kamar.

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Competing interests

H.R.D. has received travel and accommodation costs and consultancy fees from GlaxoSmithKline, Roche and Wantai; he has received travel, accommodation and lecture fees from GFE Blut GmBh, Gilead and Merck; and he has received travel and accommodation fees from the Gates Foundation and Médecins sans Frontières and a grant from the British Medical Association. All other authors declare no competing interests related to this Primer.

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Kamar, N., Izopet, J., Pavio, N. et al. Hepatitis E virus infection. Nat Rev Dis Primers 3, 17086 (2017). https://doi.org/10.1038/nrdp.2017.86

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