Hepatitis E natural history

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Natural History

Hepatitis E is often asymptomatic, particularly in children.[1] Patients in highly endemic areas often present anicteric hepatitis, without developing symptoms. In these cases, the disease is only identifiable by HEV viremia, with elevated liver enzymes and normal bilirubin levels.[2] Although the severity of the disease is poorly understood, it has been associated with an higher viral load.[3] Hepatitis E may be classified in acute and chronic disease.[4]

Acute Hepatitis E

In endemic areas, hepatitis E commonly presents as acute icteric hepatitis, similarly to other types of viral hepatitis. The clinical course of acute hepatitis E progresses according to the following phases:[5][6][7][8]

Clinical Course
Stage of Infection Symptoms
Incubation period
  • Lasts 3 to 8 weeks, with a mean of 40 days
Prodromal or Preicteric Phase
  • Lasts for a few days
  • Initial symptoms are unspecific and may include:
Symptomatic or Icteric Phase
  • Follows the disappearance of prodromal symptoms
  • Self-limited
  • Lasts a few weeks
  • Symptoms and findings may include:

Pregnant women may experience more severe cases of hepatitis, possibly progressing into hepatic failure. The more complicated course of the disease is thought to be due to the characteristic immunity and hormonal changes that occur during pregnancy.[9][10] Additionally, fatal outcomes of hepatitis E in pregnant women were associated with the decrease of progesterone receptors.[11]

Viral superinfection may occur in patients with chronic liver disease (symptomatic or asymptomatic) of any etiology. These patients may present with severe "acute on chronic" liver disease.[2][12] Superinfection and liver decompensation are associated with poor outcomes.

In areas with lower disease prevalence, hepatitis E may present as:[6]

The typical hepatitis E patient in these areas is an old male, with either alcohol consumption, or other underlying liver disease. Possibly due to the older age and existence of concomitant disorders, the mortality rate is higher in these regions.[2]

Chronic Hepatitis E

Although it might occur in immunocompetent adults, chronic disease is commonly found in immunocompromised patients, such as:[4]

Liver disease in some of these patients progresses into fibrosis and cirrhosis.[4][13][16]

Complications

Extra-Hepatic

Hepatitis E may also present with extra-hepatic manifestations, including:[4][17][18]

Newborns of Infected Mothers

Newborns from mothers infected with HEV have a mortality rate of about 50%.[19] These infants may show:[2]

  • Icteric hepatitis
  • Anicteric hepatitis

Prognosis

Hepatitis E is self-limited in most immunocompetent patients. In these cases the prognosis is often good. Immunocompromised patients, and those with end-stage liver disease are at higher risk of developing chronic hepatitis and other complications. This last group of patients have a poor prognosis.[5]

  • The mortality rate of hospitalized patients with hepatitis E is 0.5 - 4%.[2][20]
  • In developing countries, mortality rate during epidemics is 0.2 - 4.0%.[5] In these countries, mortality rate in pregnant women ranges from 10 - 25%, and is often due to fulminant hepatic failure, hemorrhage or eclampsia.[21]

.

References

  1. ↑ Buti M, Plans P, Domínguez A, Jardi R, Rodriguez Frias F, Esteban R; et al. (2008). "Prevalence of hepatitis E virus infection in children in the northeast of Spain". Clin Vaccine Immunol. 15 (4): 732–4. doi:10.1128/CVI.00014-08. PMC 2292657. PMID 18321881.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 Aggarwal R, Jameel S (2011). "Hepatitis E." Hepatology. 54 (6): 2218–26. doi:10.1002/hep.24674. PMID 21932388.
  3. ↑ Kar P, Jilani N, Husain SA, Pasha ST, Anand R, Rai A; et al. (2008). "Does hepatitis E viral load and genotypes influence the final outcome of acute liver failure during pregnancy?". Am J Gastroenterol. 103 (10): 2495–501. doi:10.1111/j.1572-0241.2008.02032.x. PMID 18785952.
  4. ↑ 4.0 4.1 4.2 4.3 Hoofnagle JH, Nelson KE, Purcell RH (2012). "Hepatitis E." N Engl J Med. 367 (13): 1237–44. doi:10.1056/NEJMra1204512. PMID 23013075.
  5. ↑ 5.0 5.1 5.2 Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J; et al. (2012). "Hepatitis E." Lancet. 379 (9835): 2477–88. doi:10.1016/S0140-6736(11)61849-7. PMID 22549046.
  6. ↑ 6.0 6.1 Dalton HR, Stableforth W, Thurairajah P, Hazeldine S, Remnarace R, Usama W; et al. (2008). "Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease". Eur J Gastroenterol Hepatol. 20 (8): 784–90. doi:10.1097/MEG.0b013e3282f5195a. PMID 18617784.
  7. ↑ Borgen K, Herremans T, Duizer E, Vennema H, Rutjes S, Bosman A; et al. (2008). "Non-travel related Hepatitis E virus genotype 3 infections in the Netherlands; a case series 2004 - 2006". BMC Infect Dis. 8: 61. doi:10.1186/1471-2334-8-61. PMC 2413240. PMID 18462508.
  8. ↑ Zhang S, Wang J, Yuan Q, Ge S, Zhang J, Xia N; et al. (2011). "Clinical characteristics and risk factors of sporadic Hepatitis E in central China". Virol J. 8: 152. doi:10.1186/1743-422X-8-152. PMC 3082222. PMID 21453549.
  9. ↑ Wedemeyer H, Pischke S, Manns MP (2012). "Pathogenesis and treatment of hepatitis e virus infection". Gastroenterology. 142 (6): 1388–1397.e1. doi:10.1053/j.gastro.2012.02.014. PMID 22537448.
  10. ↑ Navaneethan U, Al Mohajer M, Shata MT (2008). "Hepatitis E and pregnancy: understanding the pathogenesis". Liver Int. 28 (9): 1190–9. doi:10.1111/j.1478-3231.2008.01840.x. PMC 2575020. PMID 18662274.
  11. ↑ Bose PD, Das BC, Kumar A, Gondal R, Kumar D, Kar P (2011). "High viral load and deregulation of the progesterone receptor signaling pathway: association with hepatitis E-related poor pregnancy outcome". J Hepatol. 54 (6): 1107–13. doi:10.1016/j.jhep.2010.08.037. PMID 21145845.
  12. ↑ Kumar A, Aggarwal R, Naik SR, Saraswat V, Ghoshal UC, Naik S (2004). "Hepatitis E virus is responsible for decompensation of chronic liver disease in an endemic region". Indian J Gastroenterol. 23 (2): 59–62. PMID 15176538.
  13. ↑ 13.0 13.1 Kamar N, Garrouste C, Haagsma EB, Garrigue V, Pischke S, Chauvet C; et al. (2011). "Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants". Gastroenterology. 140 (5): 1481–9. doi:10.1053/j.gastro.2011.02.050. PMID 21354150.
  14. ↑ Ollier L, Tieulie N, Sanderson F, Heudier P, Giordanengo V, Fuzibet JG; et al. (2009). "Chronic hepatitis after hepatitis E virus infection in a patient with non-Hodgkin lymphoma taking rituximab". Ann Intern Med. 150 (6): 430–1. PMID 19293084.
  15. ↑ Dalton HR, Bendall RP, Keane FE, Tedder RS, Ijaz S (2009). "Persistent carriage of hepatitis E virus in patients with HIV infection". N Engl J Med. 361 (10): 1025–7. doi:10.1056/NEJMc0903778. PMID 19726781.
  16. ↑ Grewal P, Kamili S, Motamed D (2014). "Chronic hepatitis E in an immunocompetent patient: a case report". Hepatology. 59 (1): 347–8. doi:10.1002/hep.26636. PMID 23913727.
  17. ↑ Kamar N, Weclawiak H, Guilbeau-Frugier C, Legrand-Abravanel F, Cointault O, Ribes D; et al. (2012). "Hepatitis E virus and the kidney in solid-organ transplant patients". Transplantation. 93 (6): 617–23. doi:10.1097/TP.0b013e318245f14c. PMID 22298032.
  18. ↑ Kamar N, Izopet J, Cintas P, Garrouste C, Uro-Coste E, Cointault O; et al. (2010). "Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis". Am J Transplant. 10 (5): 1321–4. doi:10.1111/j.1600-6143.2010.03068.x. PMID 20346067.
  19. ↑ Khuroo MS, Kamili S, Khuroo MS (2009). "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 (7): 519–23. doi:10.1111/j.1365-2893.2009.01101.x. PMID 19228284.
  20. ↑ Naik SR, Aggarwal R, Salunke PN, Mehrotra NN (1992). "A large waterborne viral hepatitis E epidemic in Kanpur, India". Bull World Health Organ. 70 (5): 597–604. PMC 2393368. PMID 1464145.
  21. ↑ Tsega E, Krawczynski K, Hansson BG, Nordenfelt E (1993). "Hepatitis E virus infection in pregnancy in Ethiopia". Ethiop Med J. 31 (3): 173–81. PMID 8404882.

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