Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Hepatitis E

  • Author: Prospere Remy, MD; Chief Editor: BS Anand, MD  more...
 
Updated: Jul 14, 2016
 

Background

Hepatitis E is an enterically transmitted infection that is typically self-limited.[1, 2] It is caused by the hepatitis E virus (HEV) and is spread by fecally contaminated water within endemic areas or through the consumption of uncooked or undercooked meat.[3, 4, 5] Outbreaks can be epidemic and individual. Hepatitis E has many similarities with hepatitis A. Hepatitis E has been associated with chronic hepatitis in solid-organ transplant recipients, patients infected by HIV, and an individual on rituximab treatment for non-Hodgkin lymphoma.[6, 7, 8, 9] A study has shown that among patients receiving hemodialysis, the seroprevalence of anti-HEV immunoglobulin G (IgG) was found to be high. However, no evidence of chronic infection was found.[10]

The course of infection has 2 phases, the prodromal phase and the icteric phase. The infection is self-limited. Whether protective immunoglobulins develop against future reinfection remains unknown. The overall case fatality rate is 4%, although pregnant women and liver transplant recipients may be at substantially higher risk.

Therapy should be predominantly preventive, relying on clean drinking water, good sanitation, and proper personal hygiene. A successful recombinant hepatitis E vaccine has been developed.[11, 12]

Next

Etiopathophysiology

The hepatitis E virus (HEV) genome contains 3 open reading frames (ORFs). The largest, ORF-1, codes for the nonstructural proteins responsible for viral replication. ORF-2 contains genes encoding the capsid. The function of ORF-3 is unknown, but the antibodies directed against ORF-3 epitopes have been identified.

Hepatitis E results from HEV infection and is spread by fecally contaminated water within endemic areas. On the other hand, in nonendemic areas, the major mode of the spread of HEV is foodborne, especially undercooked pork.[13]

HEV is an RNA virus of the genus Hepevirus. It was discovered during electron microscopy of feces contaminated with enteric non-A, non-B hepatitis. The virus is icosahedral and nonenveloped. It has a diameter of approximately 34 nanometers, and it contains a single strand of RNA approximately 7.5 kilobases in length. Four HEV genotypes have been identified. Genotypes 1 and 2 are considered human viruses; genotypes 3 and 4 are zoonotic and have been isolated from humans and animals.[14]

Previous
Next

Epidemiology

United States statistics

Population-based surveys from 1988-1994 indicate that 21% of US adults had anti–hepatitis E virus (HEV) antibody, a rate lower than that of anti–hepatitis A virus antibody (38.3%) but higher than that of antibodies against hepatitis B (5.7%) or hepatitis C (2%).[15]

Anti-HEV antibody rates increased markedly with age, from less than 10% among persons aged 6-19 years to more than 40% among those older than 60 years. Age-adjusted rates of anti-HEV antibody were lower among blacks (14.5%) than among non-Hispanic whites (22.1%); among men who had sex with men (23.1%) than among those who did not (23.9%); among cocaine users (16.8%) than among nonusers (23.6%); and among people living in the southern United States (14.7%) than among people living in the Northeast (20.8%), Midwest (26.6%), or West (25%). Rates of anti-HEV antibody were minimally higher among men than among women (21.6% vs 20.4%). Among men who had sex with men, rates of anti-HEV antibody were lower among men with HIV infection (12.8%) than among men without HIV infection (19.2%).[16]

The route of exposure is unknown but is generally attributed to travel in endemic areas such as China, Nepal, India, southwest France, north African countries, and Borneo. Exposure to pigs and consumption of undercooked pork are other methods of spread in autochthonous (nonendemic) cases, as testing of samples of pig liver and sausage from commercial groceries in the United States identified HEV RNA in a high percentage of samples.[17]

International statistics

The global disease burden of hepatitis E has been reported to be at least 20 million cases/year with 70,000 fatalities and 3,000 stillbirths.[18] Hepatitis E has worldwide distribution, but predominating factors include tropical climates, inadequate sanitation, and poor personal hygiene. It is found most often in developing countries near the equator, in both the Eastern and Western hemispheres. Regions with a prevalence rate of more than 25% include Central America, the Middle East, and large parts of Africa and Asia.[19]  Outbreaks are associated with rainy seasons, floods, and overcrowding.

Water supply contamination with human feces is a frequent source of epidemics. The largest outbreak was reported in northeast China, with 100,000 people affected between 1986 and 1988.[20] The reservoir of HEV is unknown, but it is believed that the virus may be transmitted by animals. Waterborne epidemics of hepatitis E mainly affect young adults, the clinical attack rate being highest among those aged 15–35 years.[21] Men are clinically infected 2-5 times more commonly than women in most outbreaks.[20, 22] However, no sex difference exists in exposure to HEV.[23, 24]

Previous
Next

Prognosis

No chronic cases of acute hepatitis E have been reported. The infection is self-limited. Whether protective immunoglobulins develop against future reinfection remains unknown. The overall case fatality rate is 4%.

Among pregnant women, the case fatality rate is 20%, and this rate increases during the second and third trimesters. Reported causes of death include encephalopathy and disseminated intravascular coagulation. The rate of fulminant hepatic failure in infected pregnant women is high.

Liver transplant recipients may be at a greater risk for hepatitis E virus (HEV) infection, which can lead to chronic hepatitis and rapid progression of liver fibrosis.[25, 26] The presence of anti-HEV-IgG titer in pretransplantation measurements do not lead to protection of hepatitis E in posttransplantation patients.[27]

Previous
 
 
Contributor Information and Disclosures
Author

Prospere Remy, MD Assistant Professor of Medicine, Albert Einstein College of Medicine; Attending Physician, Department of Internal Medicine, Bronx-Lebanon Hospital Center

Prospere Remy, MD is a member of the following medical societies: American College of Physicians, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Coauthor(s)

David Widjaja, MD Attending Physician, Department of Medicine (Gastroenterology), Bronx Lebanon Hospital Center

David Widjaja, MD is a member of the following medical societies: American College of Physicians, Indonesian Medical Association

Disclosure: Nothing to disclose.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

David Eric Bernstein, MD Director of Hepatology, North Shore University Hospital; Professor of Clinical Medicine, Albert Einstein College of Medicine

David Eric Bernstein, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Kenneth D Flora, MD Adjunct Associate Professor of Medicine, Division of Gastroenterology and Hepatology, Oregon Health Sciences University School of Medicine; Consulting Staff, Department of Gastroenterology, The Oregon Clinic

Kenneth D Flora, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, and American Gastroenterological Association

Disclosure: Nothing to disclose.

Kenneth Ingram, PAC Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health and Science University School of Medicine

Disclosure: Nothing to disclose.

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Jonathan M Schwartz, MD Associate Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Oregon Health and Sciences University School of Medicine

Jonathan M Schwartz, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and American Hepato-Pancreato-Biliary Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. Mast EE, Krawczynski K. Hepatitis E: an overview. Annu Rev Med. 1996. 47:257-66. [Medline].

  2. Purdy MA, Krawczynski K. Hepatitis E. Gastroenterol Clin North Am. 1994 Sep. 23(3):537-46. [Medline].

  3. Harrison TJ. Hepatitis E virus -- an update. Liver. 1999 Jun. 19(3):171-6. [Medline].

  4. Skidmore SJ. Factors in spread of hepatitis E. Lancet. 1999 Sep 25. 354(9184):1049-50. [Medline].

  5. Kamar N, Bendall R, Legrand-Abravanel F, et al. Hepatitis E. Lancet. 2012 Jun 30. 379(9835):2477-88. [Medline].

  6. Puoti M, Moioli MC, Travi G, Rossotti R. The burden of liver disease in human immunodeficiency virus-infected patients. Semin Liver Dis. 2012 May. 32(2):103-13. [Medline].

  7. Dalton HR, Bendall RP, Keane FE, Tedder RS, Ijaz S. Persistent carriage of hepatitis E virus in patients with HIV infection. N Engl J Med. 2009 Sep 3. 361(10):1025-7. [Medline].

  8. 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 Mar 17. 150(6):430-1. [Medline].

  9. Kamar N, Selves J, Mansuy JM, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med. 2008 Feb 21. 358(8):811-7. [Medline].

  10. Harrison A, Scobie L, Crossan C, et al. Hepatitis E seroprevalence in recipients of renal transplants or haemodialysis in southwest England: a case-control study. J Med Virol. 2013 Feb. 85(2):266-71. [Medline].

  11. Shrestha MP, Scott RM, Joshi DM, et al. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med. 2007 Mar 1. 356(9):895-903. [Medline].

  12. 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 Sep 11. 376(9744):895-902. [Medline].

  13. Hoofnagle JH, Nelson KE, Purcell RH. Hepatitis E. N Engl J Med. 2012 Sep 27. 367(13):1237-44. [Medline].

  14. Mushahwar IK. Hepatitis E virus: molecular virology, clinical features, diagnosis, transmission, epidemiology, and prevention. J Med Virol. 2008 Apr. 80(4):646-58. [Medline].

  15. Kuniholm MH, Purcell RH, McQuillan GM, Engle RE, Wasley A, Nelson KE. 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 Jul 1. 200(1):48-56. [Medline].

  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 May. 35(5):1244-7. [Medline].

  17. Feagins AR, Opriessnig T, Guenette DK, Halbur PG, Meng XJ. 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 Mar 31. 123(1-2):32-7. [Medline].

  18. Rein DB, Stevens GA, Theaker J, Wittenborn JS, Wiersma ST. The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology. 2012 Apr. 55(4):988-97. [Medline].

  19. CDC. Hepatitis E FAQs for health professionals. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/hepatitis/hev/hevfaq.htm. 2015 Dec 18; Accessed: June 25, 2016.

  20. Zhuang H, Cao XY, Liu CB, Wang GM. Epidemiology of hepatitis E in China. Gastroenterol Jpn. 1991 Jul. 26 Suppl 3:135-8. [Medline].

  21. Purcell RH, Emerson SU. Hepatitis E: an emerging awareness of an old disease. J Hepatol. 2008 Mar. 48(3):494-503. [Medline].

  22. Aggarwal R, Kumar R, Pal R, Naik S, Semwal SN, Naik SR. Role of travel as a risk factor for hepatitis E virus infection in a disease-endemic area. Indian J Gastroenterol. 2002 Jan-Feb. 21(1):14-8. [Medline].

  23. Teshale EH, Grytdal SP, Howard C, et al. Evidence of person-to-person transmission of hepatitis E virus during a large outbreak in Northern Uganda. Clin Infect Dis. 2010 Apr 1. 50(7):1006-10. [Medline].

  24. Guthmann JP, Klovstad H, Boccia D, et al. A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods. Clin Infect Dis. 2006 Jun 15. 42(12):1685-91. [Medline].

  25. 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 Jan. 17(1):30-7. [Medline].

  26. Behrendt P, Steinmann E, Manns MP, Wedemeyer H. The impact of hepatitis E in the liver transplant setting. J Hepatol. 2014 Dec. 61(6):1418-29. [Medline].

  27. Buffaz C, Scholtes C, Dron AG, et al. Hepatitis E in liver transplant recipients in the Rhone-Alpes region in France. Eur J Clin Microbiol Infect Dis. 2014 Jun. 33(6):1037-43. [Medline].

  28. Kamar N, Bendall RP, Peron JM, et al. Hepatitis E virus and neurologic disorders. Emerg Infect Dis. 2011 Feb. 17(2):173-9. [Medline].

  29. Kamar N, Weclawiak H, Guilbeau-Frugier C, et al. Hepatitis E virus and the kidney in solid-organ transplant patients. Transplantation. 2012 Mar 27. 93(6):617-23. [Medline].

  30. Said B, Ijaz S, Kafatos G, et al. Hepatitis E outbreak on cruise ship. Emerg Infect Dis. 2009 Nov. 15(11):1738-44. [Medline].

  31. van Gerven NM, van der Eijk AA, Pas SD, et al. Seroprevalence of hepatitis E virus in autoimmune hepatitis patients in the Netherlands. J Gastrointestin Liver Dis. 2016 Mar. 25(1):9-13. [Medline].

  32. Kamar N, Bendall R, Legrand-Abravanel F, et al. Hepatitis E. Lancet. 2012 Jun 30. 379(9835):2477-88. [Medline].

  33. Legrand-Abravanel F, Thevenet I, Mansuy JM, et al. Good performance of immunoglobulin M assays in diagnosing genotype 3 hepatitis E virus infections. Clin Vaccine Immunol. 2009 May. 16(5):772-4. [Medline].

  34. Legrand-Abravanel F, Mansuy JM, Dubois M, et al. Hepatitis E virus genotype 3 diversity, France. Emerg Infect Dis. 2009 Jan. 15(1):110-4. [Medline].

  35. Drobeniuc J, Meng J, Reuter G, et al. Serologic assays specific to immunoglobulin M antibodies against hepatitis E virus: pangenotypic evaluation of performances. Clin Infect Dis. 2010 Aug 1. 51(3):e24-7. [Medline].

  36. Herremans M, Bakker J, Duizer E, Vennema H, Koopmans MP. Use of serological assays for diagnosis of hepatitis E virus genotype 1 and 3 infections in a setting of low endemicity. Clin Vaccine Immunol. 2007 May. 14(5):562-8. [Medline].

  37. Chionne P, Madonna E, Pisani G, et al. Evaluation of rapid tests for diagnosis of acute hepatitis E. J Clin Virol. 2016 May. 78:4-8. [Medline].

  38. Chauhan A, Jameel S, Dilawari JB, Chawla YK, Kaur U, Ganguly NK. Hepatitis E virus transmission to a volunteer. Lancet. 1993 Jan 16. 341(8838):149-50. [Medline].

  39. 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 Oct. 172(4):927-33. [Medline].

  40. Pischke S, Suneetha PV, Baechlein C, et al. Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients. Liver Transpl. 2010 Jan. 16(1):74-82. [Medline].

  41. 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. 2010 May. 82(5):799-805. [Medline].

  42. Ghabrah TM, Tsarev S, Yarbough PO, Emerson SU, Strickland GT, Purcell RH. Comparison of tests for antibody to hepatitis E virus. J Med Virol. 1998 Jun. 55(2):134-7. [Medline].

  43. Bendall R, Ellis V, Ijaz S, Thurairajah P, Dalton HR. Serological response to hepatitis E virus genotype 3 infection: IgG quantitation, avidity, and IgM response. J Med Virol. 2008 Jan. 80(1):95-101. [Medline].

  44. Innis BL, Seriwatana J, Robinson RA, et al. Quantitation of immunoglobulin to hepatitis E virus by enzyme immunoassay. Clin Diagn Lab Immunol. 2002 May. 9(3):639-48. [Medline].

  45. Agrawal V, Goel A, Rawat A, Naik S, Aggarwal R. Histological and immunohistochemical features in fatal acute fulminant hepatitis E. Indian J Pathol Microbiol. 2012 Jan-Mar. 55(1):22-7. [Medline].

  46. Malcolm P, Dalton H, Hussaini HS, Mathew J. The histology of acute autochthonous hepatitis E virus infection. Histopathology. 2007 Aug. 51(2):190-4. [Medline].

  47. Barnaud E, Rogee S, Garry P, Rose N, Pavio N. Thermal inactivation of infectious hepatitis E virus in experimentally contaminated food. Appl Environ Microbiol. 2012 Aug. 78(15):5153-9. [Medline].

  48. Zhang J, Zhang XF, Huang SJ, et al. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015 Mar 5. 372(10):914-22. [Medline].

  49. Wedemeyer H, Pischke S. Hepatitis: Hepatitis E vaccination--is HEV 239 the breakthrough?. Nat Rev Gastroenterol Hepatol. 2011 Jan. 8(1):8-10. [Medline].

  50. Gerolami R, Borentain P, Raissouni F, Motte A, Solas C, Colson P. Treatment of severe acute hepatitis E by ribavirin. J Clin Virol. 2011 Sep. 52(1):60-2. [Medline].

  51. Kamar N, Rostaing L, Abravanel F, et al. Ribavirin therapy inhibits viral replication on patients with chronic hepatitis e virus infection. Gastroenterology. 2010 Nov. 139(5):1612-8. [Medline].

  52. Kamar N, Abravanel F, Selves J, et al. Influence of immunosuppressive therapy on the natural history of genotype 3 hepatitis-E virus infection after organ transplantation. Transplantation. 2010 Feb 15. 89(3):353-60. [Medline].

  53. 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 Oct. 99(10):2124-31. [Medline].

  54. Wang Y, Zhou X, Debing Y, et al. Calcineurin inhibitors stimulate and mycophenolic acid inhibits replication of hepatitis E virus. Gastroenterology. 2014 Jun. 146(7):1775-83. [Medline].

  55. Wedemeyer H, Pischke S, Manns MP. Pathogenesis and treatment of hepatitis E virus infection. Gastroenterology. 2012 May. 142(6):1388-1397.e1. [Medline].

  56. Lhomme S, Kamar N, Nicot F, et al. Mutation in the hepatitis E virus polymerase and outcome of ribavirin therapy. Antimicrob Agents Chemother. 2015 Dec 28. 60(3):1608-14. [Medline].

  57. 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 Mar 1. 50(5):e30-3. [Medline].

  58. Haagsma EB, Riezebos-Brilman A, van den Berg AP, Porte RJ, Niesters HG. Treatment of chronic hepatitis E in liver transplant recipients with pegylated interferon alpha-2b. Liver Transpl. 2010 Apr. 16(4):474-7. [Medline].

  59. 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 Jan. 150(1):82-85.e4. [Medline].

  60. Debing Y, Moradpour D, Neyts J, Gouttenoire J. Update on hepatitis E virology: Implications for clinical practice. J Hepatol. 2016 Jul. 65(1):200-12. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.