UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Hepatitis E virus infection

Author
Kenneth E Sherman, MD, PhD
Section Editor
Adrian M Di Bisceglie, MD
Deputy Editors
Shilpa Grover, MD, MPH, AGAF
Jennifer Mitty, MD, MPH

INTRODUCTION

Hepatitis E virus (HEV) is one of the most common causes, yet least diagnosed etiologies, of acute viral hepatitis [1]. HEV infection has a global distribution, with distinct differences in transmission and disease outcomes in resource-rich versus resource-limited areas.

This topic will review the epidemiology, clinical manifestations, diagnosis, and treatment of HEV infection in adults. Other causes of viral hepatitis are discussed in detail separately. (See "Hepatitis A virus infection in adults: An overview" and "Clinical manifestations and natural history of hepatitis B virus infection" and "Clinical manifestations and natural history of chronic hepatitis C virus infection".)

VIROLOGY

Composition and structure — Hepatitis E virus (HEV) is a small, icosahedral, nonenveloped single-stranded RNA virus that is approximately 27 to 34 nm in diameter [2-6]. It has been classified as the single member of the genus Hepevirus in the family Hepeviridae [7]. Three large open reading frames (ORFs) of the positive-sense RNA of HEV have been described [8]:

The largest ORF consists of 1693 codons; it codes for nonstructural proteins that are responsible for the processing and replication of the virus, including a methyltransferase, an RNA helicase, a cysteine protease, and an RNA polymerase [9].

The second ORF is composed of 660 codons and codes for viral capsid structural proteins.

                                 

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jul 2017. | This topic last updated: Aug 21, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. GUPTA DN, SMETANA HF. The histopathology of viral hepatitis as seen in the Delhi epidemic (1955-56). Indian J Med Res 1957; 45:101.
  2. Balayan MS, Andjaparidze AG, Savinskaya SS, et al. Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology 1983; 20:23.
  3. Kane MA, Bradley DW, Shrestha SM, et al. Epidemic non-A, non-B hepatitis in Nepal. Recovery of a possible etiologic agent and transmission studies in marmosets. JAMA 1984; 252:3140.
  4. Krawczynski K, Bradley DW. Enterically transmitted non-A, non-B hepatitis: identification of virus-associated antigen in experimentally infected cynomolgus macaques. J Infect Dis 1989; 159:1042.
  5. Yamashita T, Mori Y, Miyazaki N, et al. Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure. Proc Natl Acad Sci U S A 2009; 106:12986.
  6. Guu TS, Liu Z, Ye Q, et al. Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding. Proc Natl Acad Sci U S A 2009; 106:12992.
  7. Emerson SU. Hepevirus. In: Virus Taxonomy, VIIth report of the ICTV, Fauquet CM, et al (Eds), Elsevier Academic Press, San Diego 2005. p.853.
  8. Koonin EV, Gorbalenya AE, Purdy MA, 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 U S A 1992; 89:8259.
  9. Cao D, Meng XJ. Molecular biology and replication of hepatitis E virus. Emerg Microbes Infect 2012; 1:e17.
  10. Ding Q, Heller B, Capuccino JM, et al. Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles. Proc Natl Acad Sci U S A 2017; 114:1147.
  11. Lu L, Li C, Hagedorn CH. Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis. Rev Med Virol 2006; 16:5.
  12. Xia J, Zeng H, Liu L, et al. Swine and rabbits are the main reservoirs of hepatitis E virus in China: detection of HEV RNA in feces of farmed and wild animals. Arch Virol 2015; 160:2791.
  13. World Health Organization. Hepatitis E Fact sheet (updated July 2016). http://www.who.int/mediacentre/factsheets/fs280/en/ (Accessed on June 20, 2017).
  14. Khuroo MS. Study of an epidemic of non-A, non-B hepatitis. Possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type. Am J Med 1980; 68:818.
  15. Meng XJ, Wiseman B, Elvinger F, et al. Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries. J Clin Microbiol 2002; 40:117.
  16. Thomas DL, Yarbough PO, Vlahov D, et al. Seroreactivity to hepatitis E virus in areas where the disease is not endemic. J Clin Microbiol 1997; 35:1244.
  17. Kuniholm MH, Purcell RH, McQuillan GM, 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 2009; 200:48.
  18. Tang YW, Wang JX, Xu ZY, et al. A serologically confirmed, case-control study, of a large outbreak of hepatitis A in China, associated with consumption of clams. Epidemiol Infect 1991; 107:651.
  19. Quintana A, Sanchez L, Larralde O, Anderson D. Prevalence of antibodies to hepatitis E virus in residents of a district in Havana, Cuba. J Med Virol 2005; 76:69.
  20. Lynch M, O'Flynn N, Cryan B, et al. Hepatitis E in Ireland. Eur J Clin Microbiol Infect Dis 1995; 14:1109.
  21. Sylvan SP. The high rate of antibodies to hepatitis E virus in young, intravenous drug-abusers with acute hepatitis B-virus infection in a Swedish community: a study of hepatitis markers in individuals with intravenously or sexually acquired hepatitis B-virus infection. Scand J Infect Dis 1998; 30:429.
  22. Christensen PB, Engle RE, Jacobsen SE, et al. High prevalence of hepatitis E antibodies among Danish prisoners and drug users. J Med Virol 2002; 66:49.
  23. Ibarra HV, Riedemann SG, Siegel FG, et al. Hepatitis E virus in Chile. Lancet 1994; 344:1501.
  24. Banks M, Bendall R, Grierson S, et al. Human and porcine hepatitis E virus strains, United Kingdom. Emerg Infect Dis 2004; 10:953.
  25. Stefanidis I, Zervou EK, Rizos C, et al. Hepatitis E virus antibodies in hemodialysis patients: an epidemiological survey in central Greece. Int J Artif Organs 2004; 27:842.
  26. Gessoni G, Manoni F. Hepatitis E virus infection in north-east Italy: serological study in the open population and groups at risk. J Viral Hepat 1996; 3:197.
  27. Clemente-Casares P, Pina S, Buti M, et al. Hepatitis E virus epidemiology in industrialized countries. Emerg Infect Dis 2003; 9:448.
  28. Aggarwal R. Hepatitis E: Historical, contemporary and future perspectives. J Gastroenterol Hepatol 2011; 26 Suppl 1:72.
  29. Kmush B, Wierzba T, Krain L, et al. Epidemiology of hepatitis E in low- and middle-income countries of Asia and Africa. Semin Liver Dis 2013; 33:15.
  30. Rein DB, Stevens GA, Theaker J, et al. The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology 2012; 55:988.
  31. Arankalle VA, Chadha MS, Mehendale SM, Banerjee K. Outbreak of enterically transmitted non-A, non-B hepatitis among schoolchildren. Lancet 1988; 2:1199.
  32. Belabbes EH, Bouguermouh A, Benatallah A, Illoul G. Epidemic non-A, non-B viral hepatitis in Algeria: strong evidence for its spreading by water. J Med Virol 1985; 16:257.
  33. Tsega E, Krawczynski K, Hansson BG, et al. Outbreak of acute hepatitis E virus infection among military personnel in northern Ethiopia. J Med Virol 1991; 34:232.
  34. Velázquez O, Stetler HC, Avila C, et al. Epidemic transmission of enterically transmitted non-A, non-B hepatitis in Mexico, 1986-1987. JAMA 1990; 263:3281.
  35. Green A. The omitted epidemic-hepatitis E in the Lake Chad region. Lancet 2017; 390:443.
  36. World Health Organization. Hepatitis E – Niger http://www.who.int/csr/don/05-may-2017-hepatitis-e-niger/en/ (Accessed on August 01, 2017).
  37. Atiq M, Shire NJ, Barrett A, et al. Hepatitis E virus antibodies in patients with chronic liver disease. Emerg Infect Dis 2009; 15:479.
  38. Teshale EH, Denniston MM, Drobeniuc J, et al. Decline in hepatitis E virus antibody prevalence in the United States from 1988-1994 to 2009-2010. J Infect Dis 2015; 211:366.
  39. Stramer SL, Moritz ED, Foster GA, et al. Hepatitis E virus: seroprevalence and frequency of viral RNA detection among US blood donors. Transfusion 2016; 56:481.
  40. https://ecdc.europa.eu/en/publications-data/hepatitis-e-eueea-2005-2015 (Accessed on August 01, 2017).
  41. The Lancet . Growing concerns of hepatitis E in Europe. Lancet 2017; 390:334.
  42. Naik SR, Aggarwal R, Salunke PN, Mehrotra NN. A large waterborne viral hepatitis E epidemic in Kanpur, India. Bull World Health Organ 1992; 70:597.
  43. Shata MT, Daef EA, Zaki ME, et al. Protective role of humoral immune responses during an outbreak of hepatitis E in Egypt. Trans R Soc Trop Med Hyg 2012; 106:613.
  44. Labrique AB, Zaman K, Hossain Z, et al. Epidemiology and risk factors of incident hepatitis E virus infections in rural Bangladesh. Am J Epidemiol 2010; 172:952.
  45. World Health Organization. Acute hepatitis E – Nigeria. http://www.who.int/csr/don/12-july-2017-hepatitis-e-nigeria/en/ (Accessed on August 01, 2017).
  46. Said B, Ijaz S, Kafatos G, et al. Hepatitis E outbreak on cruise ship. Emerg Infect Dis 2009; 15:1738.
  47. Karetnyi YV, Gilchrist MJ, Naides SJ. Hepatitis E virus infection prevalence among selected populations in Iowa. J Clin Virol 1999; 14:51.
  48. Romanò L, Paladini S, Tagliacarne C, et al. Hepatitis E in Italy: a long-term prospective study. J Hepatol 2011; 54:34.
  49. Ijaz S, Arnold E, Banks M, et al. Non-travel-associated hepatitis E in England and Wales: demographic, clinical, and molecular epidemiological characteristics. J Infect Dis 2005; 192:1166.
  50. Arankalle VA, Chobe LP, Joshi MV, et al. Human and swine hepatitis E viruses from Western India belong to different genotypes. J Hepatol 2002; 36:417.
  51. Rutjes SA, Lodder WJ, Lodder-Verschoor F, et al. Sources of hepatitis E virus genotype 3 in The Netherlands. Emerg Infect Dis 2009; 15:381.
  52. He J, Innis BL, Shrestha MP, et al. Evidence that rodents are a reservoir of hepatitis E virus for humans in Nepal. J Clin Microbiol 2006; 44:1208.
  53. Tei S, Kitajima N, Takahashi K, Mishiro S. Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet 2003; 362:371.
  54. Li TC, Chijiwa K, Sera N, et al. Hepatitis E virus transmission from wild boar meat. Emerg Infect Dis 2005; 11:1958.
  55. Wichmann O, Schimanski S, Koch J, et al. Phylogenetic and case-control study on hepatitis E virus infection in Germany. J Infect Dis 2008; 198:1732.
  56. Colson P, Borentain P, Queyriaux B, et al. Pig liver sausage as a source of hepatitis E virus transmission to humans. J Infect Dis 2010; 202:825.
  57. Huang F, Li Y, Yu W, et al. Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis. Hepatology 2016; 64:350.
  58. Feagins AR, Opriessnig T, Guenette DK, et al. Inactivation of infectious hepatitis E virus present in commercial pig livers sold in local grocery stores in the United States. Int J Food Microbiol 2008; 123:32.
  59. Arankalle VA, Chobe LP. Retrospective analysis of blood transfusion recipients: evidence for post-transfusion hepatitis E. Vox Sang 2000; 79:72.
  60. Matsubayashi K, Nagaoka Y, Sakata H, et al. Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan. Transfusion 2004; 44:934.
  61. Khuroo MS, Kamili S, Yattoo GN. Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area. J Gastroenterol Hepatol 2004; 19:778.
  62. Hewitt PE, Ijaz S, Brailsford SR, et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet 2014; 384:1766.
  63. Khuroo MS, Kamili S, Jameel S. Vertical transmission of hepatitis E virus. Lancet 1995; 345:1025.
  64. Kumar RM, Uduman S, Rana S, et al. Sero-prevalence and mother-to-infant transmission of hepatitis E virus among pregnant women in the United Arab Emirates. Eur J Obstet Gynecol Reprod Biol 2001; 100:9.
  65. El Sayed Zaki M, El Aal AA, Badawy A, et al. Clinicolaboratory study of mother-to-neonate transmission of hepatitis E virus in Egypt. Am J Clin Pathol 2013; 140:721.
  66. Rivero-Juarez A, Frias M, Rodriguez-Cano D, et al. Isolation of Hepatitis E Virus From Breast Milk During Acute Infection. Clin Infect Dis 2016; 62:1464.
  67. Chauhan A, Jameel S, Dilawari JB, et al. Hepatitis E virus transmission to a volunteer. Lancet 1993; 341:149.
  68. Bryan JP, Tsarev SA, Iqbal M, et al. Epidemic hepatitis E in Pakistan: patterns of serologic response and evidence that antibody to hepatitis E virus protects against disease. J Infect Dis 1994; 170:517.
  69. Zhu FC, Zhang J, Zhang XF, 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 2010; 376:895.
  70. Harun-Or-Rashid M, Akbar SM, Takahashi K, et al. Epidemiological and molecular analyses of a non-seasonal outbreak of acute icteric hepatitis E in Bangladesh. J Med Virol 2013; 85:1369.
  71. Centers for Disease Control and Prevention (CDC). Hepatitis E among U.S. travelers, 1989-1992. MMWR Morb Mortal Wkly Rep 1993; 42:1.
  72. Morrow RH Jr, Smetana HF, Sai FT, Edgcomb JH. Unusual features of viral hepatitis in Accra, Ghana. Ann Intern Med 1968; 68:1250.
  73. Herrera JL. Hepatitis E as a cause of acute non-A, non-B hepatitis. Arch Intern Med 1993; 153:773.
  74. Jameel S, Durgapal H, Habibullah CM, et al. Enteric non-A, non-B hepatitis: epidemics, animal transmission, and hepatitis E virus detection by the polymerase chain reaction. J Med Virol 1992; 37:263.
  75. Geurtsvankessel CH, Islam Z, Mohammad QD, et al. Hepatitis E and Guillain-Barre syndrome. Clin Infect Dis 2013; 57:1369.
  76. Favorov MO, Fields HA, Purdy MA, et al. Serologic identification of hepatitis E virus infections in epidemic and endemic settings. J Med Virol 1992; 36:246.
  77. Khuroo MS, Khuroo MS. Hepatitis E: an emerging global disease - from discovery towards control and cure. J Viral Hepat 2016; 23:68.
  78. Asher LV, Innis BL, Shrestha MP, et al. Virus-like particles in the liver of a patient with fulminant hepatitis and antibody to hepatitis E virus. J Med Virol 1990; 31:229.
  79. Schlosser B, Stein A, Neuhaus R, et al. Liver transplant from a donor with occult HEV infection induced chronic hepatitis and cirrhosis in the recipient. J Hepatol 2012; 56:500.
  80. Aggarwal R. Hepatitis E: clinical presentation in disease-endemic areas and diagnosis. Semin Liver Dis 2013; 33:30.
  81. Fontana RJ, Engle RE, Scaglione S, et al. The role of hepatitis E virus infection in adult Americans with acute liver failure. Hepatology 2016; 64:1870.
  82. Centers for Disease Control (CDC). Enterically transmitted non-A, non-B hepatitis--East Africa. MMWR Morb Mortal Wkly Rep 1987; 36:241.
  83. Chau TN, Lai ST, Tse C, et al. Epidemiology and clinical features of sporadic hepatitis E as compared with hepatitis A. Am J Gastroenterol 2006; 101:292.
  84. Mechnik L, Bergman N, Attali M, et al. Acute hepatitis E virus infection presenting as a prolonged cholestatic jaundice. J Clin Gastroenterol 2001; 33:421.
  85. Hoofnagle JH, Nelson KE, Purcell RH. Hepatitis E. N Engl J Med 2012; 367:1237.
  86. Ollier L, Tieulie N, Sanderson F, et al. Chronic hepatitis after hepatitis E virus infection in a patient with non-Hodgkin lymphoma taking rituximab. Ann Intern Med 2009; 150:430.
  87. Dalton HR, Bendall RP, Keane FE, et al. Persistent carriage of hepatitis E virus in patients with HIV infection. N Engl J Med 2009; 361:1025.
  88. Halac U, Béland K, Lapierre P, et al. Cirrhosis due to chronic hepatitis E infection in a child post-bone marrow transplant. J Pediatr 2012; 160:871.
  89. Passos-Castilho AM, Porta G, Miura IK, et al. Chronic hepatitis E virus infection in a pediatric female liver transplant recipient. J Clin Microbiol 2014; 52:4425.
  90. Behrendt P, Steinmann E, Manns MP, Wedemeyer H. The impact of hepatitis E in the liver transplant setting. J Hepatol 2014; 61:1418.
  91. Perumpail RB, Ahmed A, Higgins JP, et al. Fatal Accelerated Cirrhosis after Imported HEV Genotype 4 Infection. Emerg Infect Dis 2015; 21:1679.
  92. Jilani N, Das BC, Husain SA, et al. Hepatitis E virus infection and fulminant hepatic failure during pregnancy. J Gastroenterol Hepatol 2007; 22:676.
  93. Khuroo MS, Teli MR, Skidmore S, et al. Incidence and severity of viral hepatitis in pregnancy. Am J Med 1981; 70:252.
  94. Patra S, Kumar A, Trivedi SS, et al. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med 2007; 147:28.
  95. Stoszek SK, Abdel-Hamid M, Saleh DA, et al. High prevalence of hepatitis E antibodies in pregnant Egyptian women. Trans R Soc Trop Med Hyg 2006; 100:95.
  96. Navaneethan U, Al Mohajer M, Shata MT. Hepatitis E and pregnancy: understanding the pathogenesis. Liver Int 2008; 28:1190.
  97. Sehgal R, Patra S, David P, et al. Impaired monocyte-macrophage functions and defective Toll-like receptor signaling in hepatitis E virus-infected pregnant women with acute liver failure. Hepatology 2015; 62:1683.
  98. Hamid SS, Atiq M, Shehzad F, et al. Hepatitis E virus superinfection in patients with chronic liver disease. Hepatology 2002; 36:474.
  99. Kumar Acharya S, Kumar Sharma P, Singh R, et al. Hepatitis E virus (HEV) infection in patients with cirrhosis is associated with rapid decompensation and death. J Hepatol 2007; 46:387.
  100. Samala N, Wright EC, Buckler AG, et al. Hepatitis E Virus Does Not Contribute to Hepatic Decompensation Among Patients With Advanced Chronic Hepatitis C. Clin Gastroenterol Hepatol 2016; 14:896.
  101. Kamar N, Selves J, Mansuy JM, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 2008; 358:811.
  102. Haagsma EB, van den Berg AP, Porte RJ, et al. Chronic hepatitis E virus infection in liver transplant recipients. Liver Transpl 2008; 14:547.
  103. Kamar N, Mansuy JM, Cointault O, et al. Hepatitis E virus-related cirrhosis in kidney- and kidney-pancreas-transplant recipients. Am J Transplant 2008; 8:1744.
  104. Haagsma EB, Niesters HG, van den Berg AP, et al. Prevalence of hepatitis E virus infection in liver transplant recipients. Liver Transpl 2009; 15:1225.
  105. Abravanel F, Lhomme S, Chapuy-Regaud S, et al. Hepatitis E virus reinfections in solid-organ-transplant recipients can evolve into chronic infections. J Infect Dis 2014; 209:1900.
  106. Gérolami R, Moal V, Colson P. Chronic hepatitis E with cirrhosis in a kidney-transplant recipient. N Engl J Med 2008; 358:859.
  107. Khuroo MS, Khuroo MS. Hepatitis E virus. Curr Opin Infect Dis 2008; 21:539.
  108. Legrand-Abravanel F, Kamar N, Sandres-Saune K, et al. Hepatitis E virus infection without reactivation in solid-organ transplant recipients, France. Emerg Infect Dis 2011; 17:30.
  109. Kamar N, Garrouste C, Haagsma EB, et al. Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. Gastroenterology 2011; 140:1481.
  110. Suneetha PV, Pischke S, Schlaphoff V, et al. Hepatitis E virus (HEV)-specific T-cell responses are associated with control of HEV infection. Hepatology 2012; 55:695.
  111. Legrand-Abravanel F, Kamar N, Sandres-Saune K, et al. Characteristics of autochthonous hepatitis E virus infection in solid-organ transplant recipients in France. J Infect Dis 2010; 202:835.
  112. le Coutre P, Meisel H, Hofmann J, et al. Reactivation of hepatitis E infection in a patient with acute lymphoblastic leukaemia after allogeneic stem cell transplantation. Gut 2009; 58:699.
  113. Sherman KE, Terrault N, Barin B, et al. Hepatitis E infection in HIV-infected liver and kidney transplant candidates. J Viral Hepat 2014; 21:e74.
  114. Abravanel F, Lhomme S, Fougère M, et al. HEV infection in French HIV-infected patients. J Infect 2017; 74:310.
  115. Mateos-Lindemann ML, Diez-Aguilar M, Galdamez AL, et al. Patients infected with HIV are at high-risk for hepatitis E virus infection in Spain. J Med Virol 2014; 86:71.
  116. Davern TJ, Chalasani N, Fontana RJ, et al. Acute hepatitis E infection accounts for some cases of suspected drug-induced liver injury. Gastroenterology 2011; 141:1665.
  117. Pawlotsky JM. Hepatitis E screening for blood donations: an urgent need? Lancet 2014; 384:1729.
  118. Anwar N, Sherman KE. Viral hepatitis other than A, B, or C. In: Scientific American Gastroenterology, Hepatology, and Endoscopy, Burakoff R. (Ed), Decker Intellectual Properties, Toronto 2016.
  119. Baylis SA, Hanschmann KM, Blümel J, et al. Standardization of hepatitis E virus (HEV) nucleic acid amplification technique-based assays: an initial study to evaluate a panel of HEV strains and investigate laboratory performance. J Clin Microbiol 2011; 49:1234.
  120. Khudyakov Y, Kamili S. Serological diagnostics of hepatitis E virus infection. Virus Res 2011; 161:84.
  121. Emerson SU, Purcell RH. Hepatitis E. Pediatr Infect Dis J 2007; 26:1147.
  122. Favorov MO, Khudyakov YE, Mast EE, et al. IgM and IgG antibodies to hepatitis E virus (HEV) detected by an enzyme immunoassay based on an HEV-specific artificial recombinant mosaic protein. J Med Virol 1996; 50:50.
  123. Zaki Mel-S, Foud MF, Mohamed AF. Value of hepatitis E virus detection by cell culture compared with nested PCR and serological studies by IgM and IgG. FEMS Immunol Med Microbiol 2009; 56:73.
  124. El-Sayed Zaki M, El-Deen Zaghloul MH, El Sayed O. Acute sporadic hepatitis E in children: diagnostic relevance of specific immunoglobulin M and immunoglobulin G compared with nested reverse transcriptase PCR. FEMS Immunol Med Microbiol 2006; 48:16.
  125. Dawson GJ, Mushahwar IK, Chau KH, Gitnick GL. Detection of long-lasting antibody to hepatitis E virus in a US traveller to Pakistan. Lancet 1992; 340:426.
  126. Dawson GJ, Chau KH, Cabal CM, et al. Solid-phase enzyme-linked immunosorbent assay for hepatitis E virus IgG and IgM antibodies utilizing recombinant antigens and synthetic peptides. J Virol Methods 1992; 38:175.
  127. Khuroo MS, Kamili S, Dar MY, et al. Hepatitis E and long-term antibody status. Lancet 1993; 341:1355.
  128. Aggarwal R. Diagnosis of hepatitis E. Nat Rev Gastroenterol Hepatol 2013; 10:24.
  129. Khuroo MS. Hepatitis E: the enterically transmitted non-A, non-B hepatitis. Indian J Gastroenterol 1991; 10:96.
  130. Krawczynski K, McCaustland K, Mast E, et al. Elements of pathogenesis of HEV infection in man and experimentally infected primates. In: Enterically-transmitted Hepatitis Viruses, Buisson Y, Coursage P, Kane M (Eds), La Simarre, Tours, 1996. p.317.
  131. Zhuang H, CAB X-Y, Liu CB, et al. Enterically transmitted non-A, non-B hepatitis in China. In: Viral Hep C, D and E, Shikata T, Purcell RH, Uchida T (Eds), Excerpta Medica, Amsterdam 1991. p.227.
  132. Koshy A, Grover S, Hyams KC, et al. Short-term IgM and IgG antibody responses to hepatitis E virus infection. Scand J Infect Dis 1996; 28:439.
  133. Clayson ET, Myint KS, Snitbhan R, et al. Viremia, fecal shedding, and IgM and IgG responses in patients with hepatitis E. J Infect Dis 1995; 172:927.
  134. Wedemeyer H, Pischke S, Manns MP. Pathogenesis and treatment of hepatitis e virus infection. Gastroenterology 2012; 142:1388.
  135. Mirazo S, Ramos N, Mainardi V, et al. Transmission, diagnosis, and management of hepatitis E: an update. Hepat Med 2014; 6:45.
  136. Dalton HR, Kamar N. Treatment of hepatitis E virus. Curr Opin Infect Dis 2016; 29:639.
  137. Kamar N, Weclawiak H, Guilbeau-Frugier C, et al. Hepatitis E virus and the kidney in solid-organ transplant patients. Transplantation 2012; 93:617.
  138. Del Bello A, Guilbeau-Frugier C, Josse AG, et al. Successful treatment of hepatitis E virus-associated cryoglobulinemic membranoproliferative glomerulonephritis with ribavirin. Transpl Infect Dis 2015; 17:279.
  139. Dalton HR, Kamar N, van Eijk JJ, et al. Hepatitis E virus and neurological injury. Nat Rev Neurol 2016; 12:77.
  140. Blasco-Perrin H, Madden RG, Stanley A, et al. Hepatitis E virus in patients with decompensated chronic liver disease: a prospective UK/French study. Aliment Pharmacol Ther 2015; 42:574.
  141. Gerolami R, Borentain P, Raissouni F, et al. Treatment of severe acute hepatitis E by ribavirin. J Clin Virol 2011; 52:60.
  142. Péron JM, Abravanel F, Guillaume M, et al. Treatment of autochthonous acute hepatitis E with short-term ribavirin: a multicenter retrospective study. Liver Int 2016; 36:328.
  143. Aggarwal R, Jameel S. Hepatitis E. Hepatology 2011; 54:2218.
  144. Kamar N, Dalton HR, Abravanel F, Izopet J. Hepatitis E virus infection. Clin Microbiol Rev 2014; 27:116.
  145. Kamar N, Izopet J, Tripon S, et al. Ribavirin for chronic hepatitis E virus infection in transplant recipients. N Engl J Med 2014; 370:1111.
  146. Chaillon A, Sirinelli A, De Muret A, et al. Sustained virologic response with ribavirin in chronic hepatitis E virus infection in heart transplantation. J Heart Lung Transplant 2011; 30:841.
  147. Kamar N, Rostaing L, Abravanel F, et al. Ribavirin therapy inhibits viral replication on patients with chronic hepatitis e virus infection. Gastroenterology 2010; 139:1612.
  148. Mallet V, Nicand E, Sultanik P, et al. Brief communication: case reports of ribavirin treatment for chronic hepatitis E. Ann Intern Med 2010; 153:85.
  149. Goyal R, Kumar A, Panda SK, et al. Ribavirin therapy for hepatitis E virus-induced acute on chronic liver failure: a preliminary report. Antivir Ther 2012; 17:1091.
  150. Singh A, Seth R, Gupta A, et al. Chronic hepatitis E - an emerging disease in an immunocompromised host. Gastroenterol Rep (Oxf) 2016.
  151. Kamar N, Lhomme S, Abravanel F, et al. An Early Viral Response Predicts the Virological Response to Ribavirin in Hepatitis E Virus Organ Transplant Patients. Transplantation 2015; 99:2124.
  152. Kamar N, Rostaing L, Abravanel F, et al. Pegylated interferon-alpha for treating chronic hepatitis E virus infection after liver transplantation. Clin Infect Dis 2010; 50:e30.
  153. Dao Thi VL, Debing Y, Wu X, et al. Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin. Gastroenterology 2016; 150:82.
  154. Donnelly MC, Imlach SN, Abravanel F, et al. Sofosbuvir and Daclatasvir Anti-Viral Therapy Fails to Clear HEV Viremia and Restore Reactive T Cells in a HEV/HCV Co-Infected Liver Transplant Recipient. Gastroenterology 2017; 152:300.
  155. DuPont HL, Ericsson CD. Prevention and treatment of traveler's diarrhea. N Engl J Med 1993; 328:1821.
  156. Hong Y, Ruan B, Yang LH, et al. Hepatitis E virus chimeric DNA vaccine elicits immunologic response in mice. World J Gastroenterol 2005; 11:6713.
  157. Zhou YX, Lee MY, Ng JM, et al. A truncated hepatitis E virus ORF2 protein expressed in tobacco plastids is immunogenic in mice. World J Gastroenterol 2006; 12:306.
  158. Purcell RH, Nguyen H, Shapiro M, et al. Pre-clinical immunogenicity and efficacy trial of a recombinant hepatitis E vaccine. Vaccine 2003; 21:2607.
  159. Zhang M, Emerson SU, Nguyen H, et al. Recombinant vaccine against hepatitis E: duration of protective immunity in rhesus macaques. Vaccine 2002; 20:3285.
  160. Shrestha MP, Scott RM, Joshi DM, et al. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med 2007; 356:895.
  161. Zhang J, Zhang XF, Huang SJ, et al. Long-term efficacy of a hepatitis E vaccine. N Engl J Med 2015; 372:914.
  162. Tsarev SA, Tsareva TS, Emerson SU, et al. Successful passive and active immunization of cynomolgus monkeys against hepatitis E. Proc Natl Acad Sci U S A 1994; 91:10198.
  163. Khuroo MS, Dar MY. Hepatitis E: evidence for person-to-person transmission and inability of low dose immune serum globulin from an Indian source to prevent it. Indian J Gastroenterol 1992; 11:113.