History

Fact Explanation
Outbreak of similar acute symptoms. Hepatitis E is commonly transmitted by the feco-oral route, often through contaminated water. [1] As a result it's usually noticed in epidemics of varying population sizes. [2] Outbreaks are more common in areas with poor sanitation. [3] [4]
Maternal infection of Hepatitis E during pregnancy The pregnant women who are infected during the third trimester are at risk of lifelong chronic infection, and there is a risk of fetal transmission, fetal death and neonatal symptomatic or asymptomatic hepatitis as well. The risk of mortality in HEV infections in late pregnancy is very high. [5] [6] [7]
History of solid organ transplantation from a Hepatitis E antibody positive person. It has been reported that the recipients of solid organ transplantation are at risk of Hepatitis E infection. [8] [9] The recipients are managed with induced immunosuppression, so re-infection is an important contributing factor in chronic HEV state. [10]
History of immunosuppression. i.e. HIV infection, Hematological diseases such as lymphomas. Re-activation of HEV and progress to chronicity is observed in immunosuppressed patients. [11] [12] Extra-hepatic manifestations also have been seen in immunocompromised individuals. [13]
Asymptomatic incubation period Just like any other hepatotrophic viruses, HEV has an incubation period, and in this case ranging 15–60 days, with a mean of 40 days. [7]
Flu-like prodrome The typical viral hepatitis have a non-distinctive flu-like prodrome before the onset of icteric phase. [1] [16] The common symptoms are malaise, [7] fever, arthralgia, nausea and vomiting. [17]
Jaundice Yellow discoloration of the skin and sclera is due to cholestasis following acute necro-inflammation of the liver. [18] [19] [20] [21] [22]
Dark urine Due to filtering of bilirubin into urine in cholestasis.[23] [24]
Pale stools Reduced levels of stercobilinogen in stools due to cholestasis. [25] [26] [27]
Abdominal pain. Most patients complain of epigastric pain. [28] It's an acute, dull pain due to stretching of the liver capsule.
Generalized itching Pruritus is a common and disabling complication of cholestasis, [29] [30] There have been various theories proposed for the cause, deposition of bile salts in skin, and role of serotonin. [31]
Acute polyarthritis or arthralgia. It's a systemic extrahepatic [32] manifestation of HEV infection, and can be the initial presentation. [33]
Acute epigastric pain that radiates to back, relieved by bending forward, shortness of breath or abdominal swelling, probably associated with mild fever and nausea/ vomiting. Features of acute necrotizing pancreatitis: Pancreatitis is a rare but life threatening extra-hepatic complication of HEV infection. [34] This happens in the early stage of infection and since it occurs in non-fulminant infection, the prognosis is favorable. [35] [36] [37]
Purpuric rash Due to thrombocytopenia as a result of virus associated hemo-phagocytic syndrome. [38] [39] It is proposed that there is an immunological basis for it. [40]
Neurological features. There have been reported combination of various neurological symptoms i.e. inflammatory polyradiculopathy ,Guillain-Barre syndrome, mononeuritis, encephalitis, proximal myopathy [41] and amyotrophy [12]. These are consequences of extra-hepatic manifestations of the infection. Some patients improve completely, some partially and some don't improve at all. [41]
Asymptomatic Asymptomatic and anicteric infections have been reported. [7] [15] [16]
References
  1. ROSSER, Barry G. Hepatitis E: Canada welcomes the world. Can J Infect Dis. [online] 1995 Jan-Feb; 6(1): 19–20. [viewed May 3, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327902/
  2. AGGARWAL R. Hepatitis E Virus and Person-to-Person Transmission. Clin Infect Dis. [online] 2010: 51 (4): 477-478. [viewed May 3, 2014] Available at doi: 10.1086/655157
  3. AGGARWAL R and JAMEEL S. Hepatitis E. Hepatology. [online] 2011 Dec;54(6):2218-26. [viewed May 3, 2014] Available at doi: 10.1002/hep.24674.
  4. AGGARWAL R and NAIK S. Epidemiology of hepatitis E: current status. J Gastroenterol Hepatol. [online] 2009 Sep;24(9):1484-93. [viewed May 3, 2014] Available at doi: 10.1111/j.1440-1746.2009.05933.x.
  5. TESHALE EH and HU DL. Hepatitis E: Epidemiology and prevention. World J Hepatol. [online] Dec 27, 2011; 3(12): 285–291. [viewed May 3, 2014] Available at doi: 10.4254/wjh.v3.i12.285
  6. KUMAR A, BENIWAL M, KAR P, SHARMA JB and MURTHY NS. Hepatitis E in pregnancy. Int J Gynaecol Obstet. [online] 2004 Jun;85(3):240-4. [viewed May 3, 2014] Available at doi:10.1016/j.ijgo.2003.11.018
  7. HUGHES JM Ed, WILSON ME Ed, TESHALE EH, HU DJ, and HOLMBERG SD. The Two Faces of Hepatitis E Virus. Clin Infect Dis. [online] 2010; 51 (3): 328-334. [viewed May 3, 2014] Available at doi: 10.1086/653943
  8. PAS SD et al. Hepatitis E Virus Infection among Solid Organ Transplant Recipients, the Netherlands. Emerging Infectious Diseases [online] 2012; 18(5) [viewed May 3, 2014] Available at DOI: 10.3201/eid1805.111712
  9. LEGRAND-ABRAVANEL F et al. Hepatitis E Virus Infection without Reactivation in Solid-Organ Transplant Recipients, France. Emerging Infectious Diseases [online] 2011 Jan; 17(1) [viewed May 3, 2014] Available at DOI: 10.3201/eid1701.100527
  10. ABRAVANEL F, LHOMME S, CHAPUY-REGAUD S, MANSUY JM, MUSCARI F, SALLUSTO F, ROSTAING L, KAMAR N and IZOPET J. Hepatitis E Virus Reinfections in Solid-Organ-Transplant Recipients Can Evolve Into Chronic Infections. J Infect Dis. [online] 2014 Mar 11. [viewed May 3, 2014] Available at doi: 10.1093/infdis/jiu032, http://jid.oxfordjournals.org/content/early/2014/03/11/infdis.jiu032.long
  11. NELSON KE, KMUSH B and LABRIQUE AB. The epidemiology of hepatitis E virus infections in developed countries and among immunocompromised patients. Expert Rev Anti Infect Ther. [online] 2011 Dec;9(12):1133-48. [viewed May 3, 2014] Available at doi: 10.1586/eri.11.138.
  12. KABA M, RICHET H, RAVAUX I, MOREAU J, POIZOT-MARTIN I, MOTTE A, NICOLINO-BRUNET C, DIGNAT-GEORGE F, MÉNARD A, DHIVER C, BROUQUI P and COLSON P. Hepatitis E virus infection in patients infected with the human immunodeficiency virus. J Med Virol. [online] 2011 Oct;83(10):1704-16. [viewed May 3, 2014] Available at doi: 10.1002/jmv.22177.
  13. KAMAR N, ROSTAING L and IZOPET J. Hepatitis E virus infection in immunosuppressed patients: natural history and therapy. Semin Liver Dis. [online] 2013 Feb;33(1):62-70. [viewed May 3, 2014] Available at doi: 10.1055/s-0033-1338115.
  14. AGGARWAL R. Clinical presentation of hepatitis E. Virus Res. [online] 2011 Oct;161(1):15-22. [viewed May 3, 2014] Available at doi: 10.1016/j.virusres.2011.03.017.
  15. AGGARWAL R and KRAWCZYNSKI K. Hepatitis E: an overview and recent advances in clinical and laboratory research. J Gastroenterol Hepatol. [online] 2000 Jan;15(1):9-20.[viewed May 3, 2014] Available at DOI: 10.1046/j.1440-1746.2000.02006.x
  16. ARORA NK, PANDA SK, NANDA SK, ANSARI IH, JOSHI S, DIXIT R and BATHLA R. Hepatitis E infection in children: study of an outbreak. J Gastroenterol Hepatol. [online] 1999 Jun;14(6):572-7. [viewed May 3, 2014] Available at DOI: 10.1046/j.1440-1746.1999.01916.x
  17. MUSHAHWAR IK. Hepatitis E virus: molecular virology, clinical features, diagnosis, transmission, epidemiology, and prevention. J Med Virol. [online] 2008 Apr;80(4):646-58. [viewed May 3, 2014] Available at doi: 10.1002/jmv.21116.
  18. MALCOLM P, DALTON H, HUSSAINI HS and MATHEW J. The histology of acute autochthonous hepatitis E virus infection. Histopathology. [online] 2007 Aug;51(2):190-4. [viewed May 3, 2014] Available at DOI: 10.1111/j.1365-2559.2007.02756.x
  19. AGRAWAL V, GOEL A, RAWAT A, NAIK S and AGGARWAL R. Histological and immunohistochemical features in fatal acute fulminant hepatitis E. Indian J Pathol Microbiol. [online] 2012 Jan-Mar;55(1):22-7. [viewed May 3, 2014] Available at doi: 10.4103/0377-4929.94849.
  20. PERON JM, DANJOUX M, KAMAR N, MISSOURY R, POIRSON H, VINEL JP, MANSUY JM, BUREAU C, IZOPET J, BROUSSET P and SELVES J. Liver histology in patients with sporadic acute hepatitis E: a study of 11 patients from South-West France. Virchows Arch. [online] 2007 Apr;450(4):405-10. [viewed May 3, 2014] Available at DOI-10.1007/s00428-007-0382-y
  21. TAKIKAWA Y, MIYAMOTO Y, ONODERA M, KURODA H, KASAI K, MIYASAKA A, TAKAHASHI M, OKAMOTO H and SUZUKI K. Icteric acute hepatitis E with no response of immunoglobulin M class anti-hepatitis E virus antibody. Hepatol Res. [online] 2012 Nov;42(11):1146-9. [viewed May 3, 2014] Available at doi: 10.1111/j.1872-034X.2012.01023.x.
  22. HARUN-OR-RASHID M, AKBAR SM, TAKAHASHI K, AL-MAHTAB M, KHAN MS, ALIM MA, EKRAM AR, KHAN MM, ARAI M and MISHIRO S. Epidemiological and molecular analyses of a non-seasonal outbreak of acute icteric hepatitis E in Bangladesh. J Med Virol. [online] 2013 Aug;85(8):1369-76. [viewed May 3, 2014] Available at doi: 10.1002/jmv.23601.
  23. COWIE BC, ADAMOPOULOS J and KELLY H. Hepatitis E Infections, Victoria, Australia Emerg Infect Dis. [online] Mar 2005; 11(3): 482–484. [viewed May 3, 2014] Available at doi: 10.3201/eid1103.040706
  24. SAID B et al. Hepatitis E Outbreak on Cruise Ship. Emerg Infect Dis. [online] Nov 2009; 15(11): 1738–1744. [viewed May 3, 2014] Available at doi: 10.3201/eid1511.091094
  25. ARNON R and SUCHY F. Neonatal Cholestasis. In: El Zouki A, Harfi H, Nazer H, et al. Textbook of Clinical Pediatrics. Vol 3. 2nd edition. Heildelberg Dordrecht, London, New York: Springer-Verlag Berlin, Heidelberg; 2012:Chapter 205, pages 1987-2001.
  26. MCKIERNAN PJ. Neonatal cholestasis. Semin Neonatol. [online] 2002 Apr;7(2):153-65. [viewed May 3, 2014] Available at doi:10.1053/siny.2002.0103
  27. LEE WS and CHAI PF. Clinical features differentiating biliary atresia from other causes of neonatal cholestasis. Ann Acad Med Singapore. [online] 2010 Aug;39(8):648-54. [viewed May 3, 2014] Available at http://www.ncbi.nlm.nih.gov/pubmed/20838708
  28. MONTALVO VILLALBA MC, LAY LAR, CHANDRA V, BELLO CORRENDOR M, FROMETA SS, MORENO AG and JAMEEL S. Hepatitis E virus genotype 1, Cuba. Emerg Infect Dis [online]. 2008 Aug [viewed May 4, 2014]. Available from http://www.cdc.gov/EID/content/14/8/1320.htm, doi: 10.3201/eid1408.080049
  29. DECOCK S, ROELANDTS R, STEENBERGEN WV, LALEMAN W, CASSIMAN D, VERSLYPE C, FEVERY J, PELT JV and NEVENS F. Cholestasis-induced pruritus treated with ultraviolet B phototherapy: an observational case series study. J Hepatol. [online] 2012 Sep;57(3):637-41. [viewed May 3, 2014] Available at doi: 10.1016/j.jhep.2012.04.023.
  30. RAIFORD DS. Pruritus of chronic cholestasis. QJM. [online] 1995 Sep;88(9):603-7. [viewed May 4, 2014]. Available from http://qjmed.oxfordjournals.org/content/88/9/603.long
  31. BUNCHORNTAVAKUL C and REDDY KR. Pruritus in chronic cholestatic liver disease. Clin Liver Dis. [online] 2012 May;16(2):331-46. [viewed May 4, 2014] Available at doi: 10.1016/j.cld.2012.03.010.
  32. WILLIAMS TPE, KASORNDORKBUA C,HALBUR PG, HAQSHENAS G, GUENETTE DK, TOTH TE, and MENG XJ. J Clin Evidence of Extrahepatic Sites of Replication of the Hepatitis E Virus in a Swine Model. Microbiol. [online] Sep 2001; 39(9): 3040–3046. [viewed May 4, 2014] Available at doi: 10.1128/JCM.39.9.3040-3046.2001
  33. SERRATRICE J, DISDIER P, COLSON P, ENE N, DE ROUX CS and WEILLER PJ. Acute polyarthritis revealing hepatitis E. Clin Rheumatol. [online] 2007 Nov;26(11):1973-5. [viewed May 4, 2014] Available at DOI-10.1007/s10067-007-0595-0
  34. DENIEL C, COTON T, BRARDJANIAN S, GUISSET M, NICAND E and SIMON F. Acute pancreatitis: a rare complication of acute hepatitis E. J Clin Virol. [online] 2011 Jul;51(3):202-4. [viewed May 4, 2014] Available at doi: 10.1016/j.jcv.2011.04.009.
  35. BHAGAT S, WADHAWAN M, SUD R and ARORA A. Hepatitis viruses causing pancreatitis and hepatitis: a case series and review of literature. Pancreas. [online] 2008 May;36(4):424-7. [viewed May 4, 2014] Available at doi: 10.1097/MPA.0b013e31815d9d53.
  36. THAPA R, BISWAS B, MALLICK D and GHOSH A. Acute pancreatitis--complicating hepatitis E virus infection in a 7-year-old boy with glucose 6 phosphate dehydrogenase deficiency. Clin Pediatr (Phila). [online] 2009 Mar;48(2):199-201. [viewed May 4, 2014] Available at doi: 10.1177/0009922808327107.
  37. MISHRA A, SAIGAL S, GUPTA R and SARIN SK. Acute pancreatitis associated with viral hepatitis: a report of six cases with review of literature. Am J Gastroenterol. [online] 1999 Aug;94(8):2292-5. [viewed May 4, 2014] Available at doi:10.1111/j.1572-0241.1999.01318.x
  38. KAMIHIRA T, YANO K, TAMADA Y, MATSUMOTO T, MIYAZATO M, NAGAOKA S, OHATA K, ABIRU S, KOMORI A, DAIKOKU M, YATSUHASHI H and ISHIBASHI H. [Case of domestically infected hepatitis E with marked thrombocytopenia]. Nihon Shokakibyo Gakkai Zasshi. [online] 2008 Jun;105(6):841-6. [viewed May 4, 2014] Available at doi-http://dx.doi.org/10.11405/nisshoshi.105.841
  39. COLSON P, PAYRAUDEAU E, LEONNET C, DE MONTIGNY S, VILLENEUVE L, MOTTE A and TAMALET C. Severe Thrombocytopenia Associated with Acute Hepatitis E Virus Infection. J Clin Microbiol. [online] Jul 2008; 46(7): 2450–2452. [viewed May 4, 2014] Available at doi: 10.1128/JCM.02295-07
  40. SINGH NK and GANGAPPA M. Acute immune thrombocytopenia associated with hepatitis E in an adult. Am J Hematol. [online] 2007 Oct;82(10):942-3. [viewed May 4, 2014] Available at DOI: 10.1002/ajh.20960
  41. KAMAR N et al. Hepatitis E virus and neurologic disorders. Emerg Infect Dis. [online] 2011 Feb;17(2):173-9. [viewed May 4, 2014] Available at doi: 10.3201/eid1702.100856.
  42. VAN EIIK JJ et al. Neuralgic amyotrophy and hepatitis E virus infection. Neurology. [online] 2014 Feb 11;82(6):498-503. [viewed May 4, 2014] Available at doi: 10.1212/WNL.0000000000000112.

Examination

Fact Explanation
Mild fever Milder fever with other features is usually present since it causes an inflammation; hepatitis. [1] [2] [3]
Yellow discolouration of sclera and skin. It is due to cholestasis following acute necro-inflammation of the liver. [4] [5] [6] [7] [8]
Peripheral stigmata of chronic liver disease The deviation from the usual self-limiting milder acute hepatitis, HEV infection progresses to chronic hepatitis in immunodeficient patients. [1] [9] [10] [11] The expected peripheral stigmata are liver palms, spider nevi, Dupuytren's contractures, ecchymosis, parotid swelling. [12]
Tender hepatomegaly Due to the inflammation of liver parenchyma and it produces pain when liver capsule is stretched. [13]
Blood pressure Systemic complications, more commonly autonomic in nature are associated with HEV infections. [14]
References
  1. KUO VC. Hepatitis E infection. Proc (Bayl Univ Med Cent). [online] Apr 2012; 25(2): 119–120. [viewed May 4, 2014] Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310506/
  2. HUGHES JM Ed, WILSON ME Ed, TESHALE EH, HU DJ, and HOLMBERG SD. The Two Faces of Hepatitis E Virus. Clin Infect Dis. [online] 2010; 51 (3): 328-334. [viewed May 3, 2014] Available at doi: 10.1086/653943
  3. MIRAZO S, MAINARDI V, RAMOS N, GERONA S, ROCCA A and ARBIZA J. Indigenous hepatitis E virus genotype 1 infection, Uruguay [letter]. Emerg Infect Dis. [online] 2014 Jan [viewed May 3, 2014]. Available at http://dx.doi.org/10.3201/eid2001.131471
  4. MALCOLM P, DALTON H, HUSSAINI HS and MATHEW J. The histology of acute autochthonous hepatitis E virus infection. Histopathology. [online] 2007 Aug;51(2):190-4. [viewed May 3, 2014] Available at DOI: 10.1111/j.1365-2559.2007.02756.x
  5. AGRAWAL V, GOEL A, RAWAT A, NAIK S and AGGARWAL R. Histological and immunohistochemical features in fatal acute fulminant hepatitis E. Indian J Pathol Microbiol. [online] 2012 Jan-Mar;55(1):22-7. [viewed May 3, 2014] Available at doi: 10.4103/0377-4929.94849.
  6. PERON JM, DANJOUX M, KAMAR N, MISSOURY R, POIRSON H, VINEL JP, MANSUY JM, BUREAU C, IZOPET J, BROUSSET P and SELVES J. Liver histology in patients with sporadic acute hepatitis E: a study of 11 patients from South-West France. Virchows Arch. [online] 2007 Apr;450(4):405-10. [viewed May 3, 2014] Available at DOI-10.1007/s00428-007-0382-y
  7. TAKIKAWA Y, MIYAMOTO Y, ONODERA M, KURODA H, KASAI K, MIYASAKA A, TAKAHASHI M, OKAMOTO H and SUZUKI K. Icteric acute hepatitis E with no response of immunoglobulin M class anti-hepatitis E virus antibody. Hepatol Res. [online] 2012 Nov;42(11):1146-9. [viewed May 3, 2014] Available at doi: 10.1111/j.1872-034X.2012.01023.x.
  8. HARUN-OR-RASHID M, AKBAR SM, TAKAHASHI K, AL-MAHTAB M, KHAN MS, ALIM MA, EKRAM AR, KHAN MM, ARAI M and MISHIRO S. Epidemiological and molecular analyses of a non-seasonal outbreak of acute icteric hepatitis E in Bangladesh. J Med Virol. [online] 2013 Aug;85(8):1369-76. [viewed May 3, 2014] Available at doi: 10.1002/jmv.23601.
  9. KAMAR N1, DALTON HR, ABRAVANEL F and IZOPET J. Hepatitis E virus infection. Clin Microbiol Rev. [online] 2014 Jan;27(1):116-38. [viewed May 5, 2014] Available at doi: 10.1128/CMR.00057-13.
  10. HAAGSMA EB, VAN DEN BERG AP, PORTE RJ, BENNE CA, VENNEMA H, REIMERINK JH and KOOPMANS MP. Chronic hepatitis E virus infection in liver transplant recipients. Liver Transpl. [online] 2008 Apr;14(4):547-53. [viewed May 5, 2014] Available at doi: 10.1002/lt.21480.
  11. AGGARWAL R and JAMEEL S. Hepatitis E. Hepatology. [online] 2011 Dec;54(6):2218-26. [viewed May 5, 2014] Available at doi: 10.1002/hep.24674.
  12. ONYEKWERE CA, OGBERA AO and HAMEED L. Chronic liver disease and hepatic encephalopathy: Clinical profile and outcomes. Niger J Clin Pract [serial online] 2011 [viewed May 5, 2014];14:181-5. Available from: http://www.njcponline.com/text.asp?2011/14/2/181/84011
  13. BONNEY JHK et al. Fatal hepatitis E viral infection in pregnant women in Ghana: a case series. BMC Res Notes. [online] 2012; 5: 478. [viewed May 5, 2014] Available at doi: 10.1186/1756-0500-5-478
  14. NEWTON JL and JONES DE. Managing systemic symptoms in chronic liver disease. J Hepatol. [online] 2012;56 Suppl 1:S46-55. [viewed May 5, 2014] Available at doi: 10.1016/S0168-8278(12)60006-3.

Differential Diagnoses

Fact Explanation
Other hepatotrophic virus infections. There are several hepatotrophic viruses in showing the same typical symptoms once infected, and some of these are Hepatitis viruses A,B,C and D, together with CMV and EBV. Some cause a distinct acute hepatitis (all the above mentioned viruses cause acute hepatitis) or a chronic course (Hep B and C). Some patients present with acute fulminant hepatitis. Some are transmitted paraentrally, some feco-orally. Rather than relying on clinical symptoms for differential diagnoses, it's convenient to go for serological (antibodies and antigens) investigations as indicated. [1] [2] [3]
Drug induced acute hepatitis Even though clinical margins to identify drug induced hepatitis and viral hepatitis not very clear-cut, usually there is a history of ingesting a known offending drug. i.e. psychotrophics, antiepileptics, rifampicin. [4] Hepatitis E can mimic drug induced hepatitis. [5] [6] [7] A patients presenting with symptoms should be investigated for both as the diagnosis of drug-induced liver injury is not secure without testing for HEV. [7]
Alcoholic hepatitis One of the commonest cause for hepatitis and cirrhosis in the world. [8] alcoholic liver disease is a spectrum of conditions ranging from acute hepatitis to chronic cirrhosis. [8] It's a very important differential diagnosis in all patients presenting with hepatitis symptoms. [8] [9]
References
  1. MYERS RP et al. Infections with Multiple Hepatotropic Viruses: Chapter 4, Polymicrobial Diseases.. [web] [viewed May 6, 2014] Available from http://www.ncbi.nlm.nih.gov/books/NBK2492/
  2. KUMAR M, JAIN S, SHARMA BC and SARIN SK. Differentiating acute hepatitis B from the first episode of symptomatic exacerbation of chronic hepatitis B. Dig Dis Sci. [online] 2006 Mar;51(3):594-9. [viewed May 6, 2014] Available from DOI 10.1007/s10620-006-3175-2
  3. HAN Y1, TANG Q, ZHU W, ZHANG X and YOU L. Clinical, biochemical, immunological and virological profiles of, and differential diagnosis between, patients with acute hepatitis B and chronic hepatitis B with acute flare. J Gastroenterol Hepatol.. [online] 2008 Nov;23(11):1728-33. [viewed May 6, 2014] Available from doi: 10.1111/j.1440-1746.2008.05600.x.
  4. MARTÍ L1, DEL OLMO JA, TOSCA J, ORNIA E, GARCÍA-TORRES ML, SERRA MA, RODRÍGUEZ F, LLUCH P, ESCUDERO A and RODRIGO JM. Clinical evaluation of drug-induced hepatitis. Rev Esp Enferm Dig. . [online] 2005 Apr;97(4):258-65. [viewed May 6, 2014] Available from http://www.ncbi.nlm.nih.gov/pubmed/15982181
  5. CHEN EY1, BAUM K, COLLINS W, LÖVE A, MERZ M, OLAFSSON S, BJÖRNSSON ES and LEE WM. Hepatitis E masquerading as drug-induced liver injury. Hepatology. . [online] 2012 Dec;56(6):2420-3. [viewed May 6, 2014] Available from doi: 10.1002/hep.26158.
  6. ISHIWATA S1, TAKAGI H, HOSHINO T, NAGANUMA A, SAKAMOTO N, KOITABASHI E, SOUMA H, INUI M, KUDO T, OGAWA A, TAHARA H, KANEKO M and OKAMOTO H. [A case of hepatitis E differentially diagnosed from drug-induced liver injury]. Nihon Shokakibyo Gakkai Zasshi. . [online] 2012 Apr;109(4):624-9. [viewed May 6, 2014] Available from http://dx.doi.org/10.11405/nisshoshi.109.624
  7. DALTON HR1, FELLOWS HJ, STABLEFORTH W, JOSEPH M, THURAIRAJAH PH, WARSHOW U, HAZELDINE S, REMNARACE R, IJAZ S, HUSSAINI SH and BENDALL RP. The role of hepatitis E virus testing in drug-induced liver injury. Aliment Pharmacol Ther. . [online] 2007 Nov 15;26(10):1429-35. [viewed May 6, 2014] Available from DOI: 10.1111/j.1365-2036.2007.03504.x
  8. BRUHA R1, DVORAK K and PETRTYL J. Alcoholic liver disease. World J Hepatol. . [online] 2012 Mar 27;4(3):81-90. [viewed May 6, 2014] Available from doi: 10.4254/wjh.v4.i3.81.
  9. MANN RE1, SMART RG and GOVONI R. The epidemiology of alcoholic liver disease. Alcohol Res Health. . [online] 2003;27(3):209-19. [viewed May 6, 2014] Available from http://www.ncbi.nlm.nih.gov/pubmed/15535449

Investigations - for Diagnosis

Fact Explanation
Liver enzyme profile Transaminases are elevated in acute hepatitis[1] [2] ,due to necro-inflammation of hepatocytes. [3] Usually like in other viral hepatitis types, it can be markedly elevated above the upper limit of normal. [4] Serum Alkaline phosphatase can also be mildly elevated. [4]
Serum bilirubin level. Bilirubin is markedly elevated, usually above >20 mg/ dl. [4] [5] [6] It peaks at 2-3 weeks. [7]
Anti-HEV immunoglobulin M In the acute infection, enzyme immunoassay shows that anti-HEV immunoglobulin M becomes detectable days before the onset of symptoms and disappears during a 4–6 month period. [4] [8] [9]
Anti-HEV immunoglobin G The IgG response for Hepatitis E (Anti-HEV IgG) appears soon after the IgM response and may persist up to 12 years after infection. [4] [8] [9]
HEV RNA Nucleic acid amplification tests for detection of viral RNA in serum and stool samples can be used to identify HEV RNA in infected individuals. It's detectable in blood at the peak of abnormal liver function tests starting from 2 weeks before to 1 week after onset of jaundice. HEV RNA appeared in stool later than in blood and disappeared from stool 2 weeks after it became undetectable in blood. [4] [10] [11] [13] Testing for antigen (RNA) together with anti-HEV IgM is the best tool for diagnosis. [12]
References
  1. VOLLMER T., DIEKMANN J., JOHNE R., EBERHARDT M., KNABBE C., DREIER J.. Novel Approach for Detection of Hepatitis E Virus Infection in German Blood Donors. Journal of Clinical Microbiology [online] December, 50(8):2708-2713 [viewed 12 May 2014] Available from: doi:10.1128/JCM.01119-12
  2. GOTANDA YUHKO, IWATA AKIKO, OHNUMA HITOSHI, YOSHIKAWA AKIRA, MIZOGUCHI HIDEAKI, ENDO KAZUNORI, TAKAHASHI MASAHARU, OKAMOTO HIROAKI. Ongoing subclinical infection of hepatitis E virus among blood donors with an elevated alanine aminotransferase level in Japan. J. Med. Virol. [online] December, 79(6):734-742 [viewed 12 May 2014] Available from: doi:10.1002/jmv.20834
  3. GAUSS ANNIKA, WENZEL JUERGEN J, FLECHTENMACHER CHRISTA, NAVID MOJDEH, EISENBACH CHRISTOPH, JILG WOLFGANG, STREMMEL WOLFGANG, SCHNITZLER PAUL. Chronic hepatitis E virus infection in a patient with leukemia and elevated transaminases: a case report. Array [online] 2012 December [viewed 12 May 2014] Available from: doi:10.1186/1752-1947-6-334
  4. TESHALE EYASU H., HU DALE J., HOLMBERG SCOTT D.. The Two Faces of Hepatitis E Virus. CLIN INFECT DIS [online] 2010 August, 51(3):328-334 [viewed 12 May 2014] Available from: doi:10.1086/653943
  5. MECHNIK L, BERGMAN N, ATTALI M, BEERGABEL M, MOSENKIS B, SOKOLOWSKI N, MALNICK S. Acute hepatitis E virus infection presenting as a prolonged cholestatic jaundice. J Clin Gastroenterol [online] 2001 Nov-Dec, 33(5):421-2 [viewed 12 May 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11606863
  6. MOUCARI RAMI, BERNUAU JACQUES, NICAND ELISABETH, CAZALS-HATEM DOMINIQUE, VALLA DOMINIQUE, MARCELLIN PATRICK, ASSELAH TARIK. Acute hepatitis E with severe jaundice: report of three cases. European Journal of Gastroenterology & Hepatology [online] 2007 November, 19(11):1012-1015 [viewed 12 May 2014] Available from: doi:10.1097/MEG.0b013e328209414d
  7. MONGA A et al. Case report: Acute hepatitis E infection with coexistent glucose-6-phosphate dehydrogenase deficiency. Can J Infect Dis. [online] 2003 Jul-Aug; 14(4): 230–231. [viewed 12 May 2014] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094938/
  8. ZHANG JUN, LI SHAO-WEI, WU TING, ZHAO QINJIAN, NG MUN-HON, XIA NING-SHAO. Hepatitis E virus: neutralizing sites, diagnosis, and protective immunity. Rev. Med. Virol. [online] December, 22(5):339-349 [viewed 12 May 2014] Available from: doi:10.1002/rmv.1719
  9. ZHANG J.-Z., IM STANLEY W.K., LAU S.H., CHAU T.N., LAI S.T., NG S.P., PEIRIS MALIK, TSE CINDY, NG T.K., NG M.H.. Occurrence of hepatitis E virus IgM, low avidity IgG serum antibodies, and viremia in sporadic cases of non-A, -B, and -C acute hepatitis. J. Med. Virol. [online] December, 66(1):40-48 [viewed 12 May 2014] Available from: doi:10.1002/jmv.2109
  10. LI X., KAMILI S., KRAWCZYNSKI K.. Quantitative detection of hepatitis E virus RNA and dynamics of viral replication in experimental infection. J Viral Hepat [online] 2006 December, 13(12):835-839 [viewed 12 May 2014] Available from: doi:10.1111/j.1365-2893.2006.00754.x
  11. AGGARWAL RAKESH, MCCAUSTLAND KAREN A.. Hepatitis E virus RNA detection in serum and feces specimens with the use of microspin columns. Journal of Virological Methods [online] 1998 October, 74(2):209-213 [viewed 12 May 2014] Available from: doi:10.1016/S0166-0934(98)00049-4
  12. ZHAO CHENYAN, LI LUPING, HARRISON TIM J., WANG QIN, SONG AIJING, FAN JINPING, MA HONGXA, ZHANG CHUNTAO, WANG YOUCHUN. Relationships among viral diagnostic markers and markers of liver function in acute hepatitis E. J Gastroenterol [online] December, 44(2):139-145 [viewed 12 May 2014] Available from: doi:10.1007/s00535-008-2281-7
  13. BAYLIS S. A., HANSCHMANN K.-M., BLUMEL J., NUBLING C. M.. 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. Journal of Clinical Microbiology [online] December, 49(4):1234-1239 [viewed 12 May 2014] Available from: doi:10.1128/JCM.02578-10

Management - General Measures

Fact Explanation
Primary prevention. There is no specific treatment option for acute hepatitis E as it's a self-limiting condition. [1] However prevention by ensuring that the water and food sources are clean, can reduce the incidence. [1] [2] [3] [4]
References
  1. AGGARWAL RAKESH, KRAWCZYNSKI KRZYSZTOF. Hepatitis E: An overview and recent advances in clinical and laboratory research. J Gastroenterol Hepatol [online] 2000 January, 15(1):9-20 [viewed 12 May 2014] Available from: doi:10.1046/j.1440-1746.2000.02006.x
  2. MUSHAHWAR ISA K.. Hepatitis E virus: Molecular virology, clinical features, diagnosis, transmission, epidemiology, and prevention. J. Med. Virol. [online] December, 80(4):646-658 [viewed 12 May 2014] Available from: doi:10.1002/jmv.21116
  3. TESHALE EYASU H. Hepatitis E: Epidemiology and prevention. WJH [online] 2011 December [viewed 12 May 2014] Available from: doi:10.4254/wjh.v3.i12.285
  4. CORNBERG M., MANNS M.P.. . Internist [online] December, 52(3):250-264 [viewed 12 May 2014] Available from: doi:10.1007/s00108-010-2678-2

Management - Specific Treatments

Fact Explanation
Hepatitis E vaccine A recombinant subunit vaccine has been formed though there are contradictions for it's use. The length of protected time is still not defined. [1] [2] [3] [4] [5] Some studies have proven good outcomes from the vaccine. [6] Vaccination in the time of epidemics are known to reduce mortality. [7]
Ribavirin therapy The antiviral Ribavarin is proven in treatment of both acute and chronic hepatitis E. 21 days have been proved to be enough for recovery. [8] [9] [10] Ribavirin should be considered in immunosuppressed patients when the immuno-suppressive drugs cannot be lowered. [11]
References
  1. AGGARWAL RAKESH, JAMEEL SHAHID. Hepatitis E vaccine. Hepatol Int [online] December, 2(3):308-315 [viewed 12 May 2014] Available from: doi:10.1007/s12072-008-9071-4
  2. LABRIQUE ALAIN B., SIKDER SHEGUFTA S., KRAIN LISA J., WEST KEITH P., CHRISTIAN PARUL, RASHID MAHBUBUR, NELSON KENRAD E.. Hepatitis E, a Vaccine-Preventable Cause of Maternal Deaths. Emerg. Infect. Dis. [online] 2012 September, 18(9):1401-1404 [viewed 12 May 2014] Available from: doi:10.3201/eid1809.120241
  3. AGGARWAL RAKESH. Hepatitis E: Historical, contemporary and future perspectives. [online] December, 26:72-82 [viewed 12 May 2014] Available from: doi:10.1111/j.1440-1746.2010.06540.x
  4. ZHAO QINJIAN, ZHANG JUN, WU TING, LI SHAO-WEI, NG MUN-HON, XIA NING-SHAO, SHIH JAMES WAI-KUO. Antigenic determinants of hepatitis E virus and vaccine-induced immunogenicity and efficacy. J Gastroenterol [online] December, 48(2):159-168 [viewed 12 May 2014] Available from: doi:10.1007/s00535-012-0701-1
  5. SAFARY ASSAD. Perspectives of Vaccination against Hepatitis E. Intervirology [online] 2001 December, 44(2-3):162-166 [viewed 12 May 2014] Available from: doi:10.1159/000050043
  6. ZHU FENG-CAI, ZHANG JUN, ZHANG XUE-FENG, ZHOU CHENG, WANG ZHONG-ZE, HUANG SHOU-JIE, WANG HUA, YANG CHANG-LIN, JIANG HAN-MIN, CAI JIA-PING, WANG YI-JUN, AI XING, HU YUE-MEI, TANG QUAN, YAO XIN, YAN QIANG, XIAN YANG-LING, WU TING, LI YI-MIN, MIAO JI, NG MUN-HON, SHIH JAMES WAI-KUO, XIA NING-SHAO. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. The Lancet [online] 2010 September, 376(9744):895-902 [viewed 12 May 2014] Available from: doi:10.1016/S0140-6736(10)61030-6
  7. YEUNG LATIFA T. F., ROBERTS EVE A.. Current issues in the management of paediatric viral hepatitis. [online] 2010 January, 30(1):5-18 [viewed 12 May 2014] Available from: doi:10.1111/j.1478-3231.2009.02145.x
  8. GEROLAMI RENé, BORENTAIN PATRICK, RAISSOUNI FERDAOUS, MOTTE ANNE, SOLAS CAROLINE, COLSON PHILIPPE. Treatment of severe acute hepatitis E by ribavirin. Journal of Clinical Virology [online] 2011 September, 52(1):60-62 [viewed 12 May 2014] Available from: doi:10.1016/j.jcv.2011.06.004
  9. KAMAR NASSIM, ROSTAING LIONEL, ABRAVANEL FLORENCE, GARROUSTE CYRIL, LHOMME SEBASTIEN, ESPOSITO LAURE, BASSE GRéGOIRE, COINTAULT OLIVIER, RIBES DAVID, NOGIER MARIE BéATRICE, ALRIC LAURENT, PERON JEAN MARIE, IZOPET JACQUES. Ribavirin Therapy Inhibits Viral Replication on Patients With Chronic Hepatitis E Virus Infection. Gastroenterology [online] 2010 November, 139(5):1612-1618 [viewed 12 May 2014] Available from: doi:10.1053/j.gastro.2010.08.002
  10. KAMAR NASSIM, IZOPET JACQUES, TRIPON SIMONA, BISMUTH MICHAEL, HILLAIRE SOPHIE, DUMORTIER JéRôME, RADENNE SYLVIE, COILLY AUDREY, GARRIGUE VALéRIE, D'ALTEROCHE LOUIS, BUCHLER MATTHIAS, COUZI LIONEL, LEBRAY PASCAL, DHARANCY SEBASTIEN, MINELLO ANNE, HOURMANT MARYVONNE, ROQUE-AFONSO ANNE-MARIE, ABRAVANEL FLORENCE, POL STANISLAS, ROSTAING LIONEL, MALLET VINCENT. Ribavirin for Chronic Hepatitis E Virus Infection in Transplant Recipients. N Engl J Med [online] 2014 March, 370(12):1111-1120 [viewed 12 May 2014] Available from: doi:10.1056/NEJMoa1215246
  11. ABBAS ZAIGHAM, AFZAL RAFIA. Hepatitis E: when to treat and how to treat. Antivir Ther [online] December, 19(2):125-131 [viewed 12 May 2014] Available from: doi:10.3851/IMP2705