Hepatitis E natural history: Difference between revisions

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==Overview==
==Overview==
Most patients with the acute form of hepatitis E are [[asymptomatic]]. Acute hepatitis E progresses according to the following stages: incubation, which usually lasts a mean of 40 days; prodrome or preicteric phase; and symptomatic or icteric phase.  The prodromal phase starts with unspecific symptoms, such as [[fever]], [[weakness]], [[malaise]], [[anorexia]], [[nausea]] and [[vomiting]], and [[abdominal pain]].  The icteric phase usually begins with [[jaundice]], follows the offset of the prodromal symptoms, and may include [[cholestasis|cholestatic symptoms]], such as [[acholic stools]] and dark-colored urine.  Pregnant women may experience more severe forms of the disease, possibly progressing into [[hepatic failure]].  Chronic hepatitis E is commonly found in [[immunocompromised]] patients, such as those infected with [[HIV]], undergoing [[chemotherapy]], or with a history of [[organ transplant]].  [[Complications]] of hepatitis E may include: [[cirrhosis]] and liver failure. Extra-hepatic [[complications]] may also be noted: [[peripheral neuropathy]]; [[encephalitis]]; acute transverse [[myelitis]]; and [[Guillain-Barré syndrome]]. The [[prognosis]] of hepatitis E is good in [[asymptomatic]] cases, however, [[immunocompromised]] patients and pregnant women have higher [[mortality rate]]s.


==Natural History==
==Natural History==
Children with hepatitis E are often [[asymptomatic]].<ref name="pmid18321881">{{cite journal| author=Buti M, Plans P, Domínguez A, Jardi R, Rodriguez Frias F, Esteban R et al.| title=Prevalence of hepatitis E virus infection in children in the northeast of Spain. | journal=Clin Vaccine Immunol | year= 2008 | volume= 15 | issue= 4 | pages= 732-4 | pmid=18321881 | doi=10.1128/CVI.00014-08 | pmc=PMC2292657 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18321881  }} </ref>
Hepatitis E is often [[asymptomatic]], particularly in children.<ref name="pmid18321881">{{cite journal| author=Buti M, Plans P, Domínguez A, Jardi R, Rodriguez Frias F, Esteban R et al.| title=Prevalence of hepatitis E virus infection in children in the northeast of Spain. | journal=Clin Vaccine Immunol | year= 2008 | volume= 15 | issue= 4 | pages= 732-4 | pmid=18321881 | doi=10.1128/CVI.00014-08 | pmc=PMC2292657 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18321881 }} </ref> 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.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388  }} </ref> Although the severity of the disease is poorly understood, it has been associated with an higher [[viral load]].<ref name="pmid18785952">{{cite journal| author=Kar P, Jilani N, Husain SA, Pasha ST, Anand R, Rai A et al.| title=Does hepatitis E viral load and genotypes influence the final outcome of acute liver failure during pregnancy? | journal=Am J Gastroenterol | year= 2008 | volume= 103 | issue= 10 | pages= 2495-501 | pmid=18785952 | doi=10.1111/j.1572-0241.2008.02032.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18785952 }} </ref>
Hepatitis E may be classified in acute and chronic disease.<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075  }} </ref>
Hepatitis E may be classified in acute and chronic disease.<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075  }} </ref>


===Acute Hepatitis E===
===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:<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046  }} </ref><ref name="pmid18617784">{{cite journal| author=Dalton HR, Stableforth W, Thurairajah P, Hazeldine S, Remnarace R, Usama W et al.| title=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. | journal=Eur J Gastroenterol Hepatol | year= 2008 | volume= 20 | issue= 8 | pages= 784-90 | pmid=18617784 | doi=10.1097/MEG.0b013e3282f5195a | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18617784  }} </ref><ref name="pmid18462508">{{cite journal| author=Borgen K, Herremans T, Duizer E, Vennema H, Rutjes S, Bosman A et al.| title=Non-travel related Hepatitis E virus genotype 3 infections in the Netherlands; a case series 2004 - 2006. | journal=BMC Infect Dis | year= 2008 | volume= 8 | issue=  | pages= 61 | pmid=18462508 | doi=10.1186/1471-2334-8-61 | pmc=PMC2413240 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18462508  }} </ref><ref name="pmid21453549">{{cite journal| author=Zhang S, Wang J, Yuan Q, Ge S, Zhang J, Xia N et al.| title=Clinical characteristics and risk factors of sporadic Hepatitis E in central China. | journal=Virol J | year= 2011 | volume= 8 | issue=  | pages= 152 | pmid=21453549 | doi=10.1186/1743-422X-8-152 | pmc=PMC3082222 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21453549  }} </ref>
In '''endemic areas''', hepatitis E commonly presents as anicteric hepatitis, or as acute icteric hepatitis.  The clinical course of acute hepatitis E progresses according to the following phases:<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046  }} </ref><ref name="pmid18617784">{{cite journal| author=Dalton HR, Stableforth W, Thurairajah P, Hazeldine S, Remnarace R, Usama W et al.| title=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. | journal=Eur J Gastroenterol Hepatol | year= 2008 | volume= 20 | issue= 8 | pages= 784-90 | pmid=18617784 | doi=10.1097/MEG.0b013e3282f5195a | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18617784  }} </ref><ref name="pmid18462508">{{cite journal| author=Borgen K, Herremans T, Duizer E, Vennema H, Rutjes S, Bosman A et al.| title=Non-travel related Hepatitis E virus genotype 3 infections in the Netherlands; a case series 2004 - 2006. | journal=BMC Infect Dis | year= 2008 | volume= 8 | issue=  | pages= 61 | pmid=18462508 | doi=10.1186/1471-2334-8-61 | pmc=PMC2413240 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18462508  }} </ref><ref name="pmid21453549">{{cite journal| author=Zhang S, Wang J, Yuan Q, Ge S, Zhang J, Xia N et al.| title=Clinical characteristics and risk factors of sporadic Hepatitis E in central China. | journal=Virol J | year= 2011 | volume= 8 | issue=  | pages= 152 | pmid=21453549 | doi=10.1186/1743-422X-8-152 | pmc=PMC3082222 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21453549  }} </ref><ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388  }} </ref>
*'''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:


::*[[Fever]]
{| style="border: 2px solid #DCDCDC; font-size: 90%; width: 50%;"
::*[[Weakness]]
|+ '''Clinical Course'''
::*[[Myalgia]]
|-
::*[[Arthralgia]]
! style="width: 75px; background: #4479BA; text-align: center;"|{{fontcolor|#FFF|Stage of Infection}}
::*[[Anorexia]]
! style="width: 200px; background: #4479BA; text-align: center;"| {{fontcolor|#FFF|Symptoms}}
::*[[Dysgeusia]]
|-
::*[[Nausea]]
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''Incubation period'''
::*[[Vomiting]]
| style="background: #DCDCDC; padding: 5px;"|
::*[[Abdominal pain]]
*Lasts 3 to 8 weeks, with a mean of 40 days
::*[[Diarrhea]]
*[[Viremia]] begins 1 to 2 weeks before [[symptom]] onset
 
*HEV [[antigens]] appear on host's [[hepatocytes]] 7 days after [[infection]]
*'''Symptomatic period'''
|-
:*More specific [[symptoms]] may include:
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''Prodromal or Preicteric Phase'''
::*[[Jaundice]]
| style="background: #DCDCDC; padding: 5px;"|
*Lasts for a few days
*[[Viremia]] lasts for few weeks after [[symptom]] onset
*Initial symptoms are unspecific and may include:
:*[[Fever]]
:*[[Weakness]]
:*[[Myalgia]]
:*[[Arthralgia]]
:*[[Anorexia]]
:*[[Dysgeusia]]
:*[[Nausea]]
:*[[Vomiting]]
:*[[Abdominal pain]]
:*[[Diarrhea]]
|-
| style="background: #F5F5F5; padding: 5px; text-align: center;"| '''Symptomatic or Icteric Phase'''
| style="background: #DCDCDC; padding: 5px;"|
*Follows the disappearance of prodromal symptoms
*Self-limited
*Lasts a few weeks
*Symptoms and findings may include:
:*[[Jaundice]]
:*[[Cholestasis]], marked by:
::*[[Itching]]
::*[[Itching]]
::*[[Acholic stools]]
::*[[Acholic stools]]
::*Dark-colored urine
::*Dark-colored urine
:*[[Hepatomegaly]]
:*Mild [[splenomegaly]]
|-
|}
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]].<ref name="pmid22537448">{{cite journal| author=Wedemeyer H, Pischke S, Manns MP| title=Pathogenesis and treatment of hepatitis e virus infection. | journal=Gastroenterology | year= 2012 | volume= 142 | issue= 6 | pages= 1388-1397.e1 | pmid=22537448 | doi=10.1053/j.gastro.2012.02.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22537448  }} </ref><ref name="pmid18662274">{{cite journal| author=Navaneethan U, Al Mohajer M, Shata MT| title=Hepatitis E and pregnancy: understanding the pathogenesis. | journal=Liver Int | year= 2008 | volume= 28 | issue= 9 | pages= 1190-9 | pmid=18662274 | doi=10.1111/j.1478-3231.2008.01840.x | pmc=PMC2575020 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18662274  }} </ref> Additionally, fatal outcomes of hepatitis E in pregnant women were associated with the decrease of [[progesterone receptor]]s.<ref name="pmid21145845">{{cite journal| author=Bose PD, Das BC, Kumar A, Gondal R, Kumar D, Kar P| title=High viral load and deregulation of the progesterone receptor signaling pathway: association with hepatitis E-related poor pregnancy outcome. | journal=J Hepatol | year= 2011 | volume= 54 | issue= 6 | pages= 1107-13 | pmid=21145845 | doi=10.1016/j.jhep.2010.08.037 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21145845  }} </ref>
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.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388  }} </ref><ref name="pmid15176538">{{cite journal| author=Kumar A, Aggarwal R, Naik SR, Saraswat V, Ghoshal UC, Naik S| title=Hepatitis E virus is responsible for decompensation of chronic liver disease in an endemic region. | journal=Indian J Gastroenterol | year= 2004 | volume= 23 | issue= 2 | pages= 59-62 | pmid=15176538 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15176538  }} </ref> [[Superinfection]] and liver decompensation are associated with poor [[outcome]]s.
In '''areas with lower disease prevalence''', hepatitis E may present as:<ref name="pmid18617784">{{cite journal| author=Dalton HR, Stableforth W, Thurairajah P, Hazeldine S, Remnarace R, Usama W et al.| title=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. | journal=Eur J Gastroenterol Hepatol | year= 2008 | volume= 20 | issue= 8 | pages= 784-90 | pmid=18617784 | doi=10.1097/MEG.0b013e3282f5195a | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18617784  }} </ref>
*Icteric hepatitis
*Anicteric hepatitis, with unspecific [[symptoms]]
*[[Asymptomatic]] disease, with [[transaminase]] elevation
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.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388  }} </ref>


Pregnant women, and patients with end-stage [[liver disease]] may experience more severe cases of hepatitis, possibly progressing into [[hepatic failure]].  The more complicated course of the disease in pregnant women is thought to be due to the characteristic immunity and hormonal changes that occur during pregnancy.<ref name="pmid22537448">{{cite journal| author=Wedemeyer H, Pischke S, Manns MP| title=Pathogenesis and treatment of hepatitis e virus infection. | journal=Gastroenterology | year= 2012 | volume= 142 | issue= 6 | pages= 1388-1397.e1 | pmid=22537448 | doi=10.1053/j.gastro.2012.02.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22537448  }} </ref><ref name="pmid18662274">{{cite journal| author=Navaneethan U, Al Mohajer M, Shata MT| title=Hepatitis E and pregnancy: understanding the pathogenesis. | journal=Liver Int | year= 2008 | volume= 28 | issue= 9 | pages= 1190-9 | pmid=18662274 | doi=10.1111/j.1478-3231.2008.01840.x | pmc=PMC2575020 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18662274  }} </ref> Additionally, fatal outcomes of hepatitis E in pregnant women were associated with the decrease of [[progesterone receptor]]s.<ref name="pmid21145845">{{cite journal| author=Bose PD, Das BC, Kumar A, Gondal R, Kumar D, Kar P| title=High viral load and deregulation of the progesterone receptor signaling pathway: association with hepatitis E-related poor pregnancy outcome. | journal=J Hepatol | year= 2011 | volume= 54 | issue= 6 | pages= 1107-13 | pmid=21145845 | doi=10.1016/j.jhep.2010.08.037 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21145845  }} </ref>
===Chronic Hepatitis E===
===Chronic Hepatitis E===
Chronic infection is defined by detection of HEV [[RNA]] in blood, or in stool, for more than 6 months. The predominant [[genotype]] causing chronic infection is HEV3, as HEV 1 and HEV 2 have not been reported in chronic disease.<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046  }} </ref>  Although it might occur in [[immunocompetent]] adults, chronic disease is commonly found in [[immunocompromised]] patients, such as:<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075  }} </ref>
*Persons with [[organ transplant]]s<ref name="pmid21354150">{{cite journal| author=Kamar N, Garrouste C, Haagsma EB, Garrigue V, Pischke S, Chauvet C et al.| title=Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. | journal=Gastroenterology | year= 2011 | volume= 140 | issue= 5 | pages= 1481-9 | pmid=21354150 | doi=10.1053/j.gastro.2011.02.050 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21354150  }} </ref>
*Persons undergoing [[chemotherapy]]<ref name="pmid19293084">{{cite journal| author=Ollier L, Tieulie N, Sanderson F, Heudier P, Giordanengo V, Fuzibet JG et al.| title=Chronic hepatitis after hepatitis E virus infection in a patient with non-Hodgkin lymphoma taking rituximab. | journal=Ann Intern Med | year= 2009 | volume= 150 | issue= 6 | pages= 430-1 | pmid=19293084 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19293084  }} </ref>
*Persons infected with [[HIV]], with low [[CD4]] counts<ref name="pmid19726781">{{cite journal| author=Dalton HR, Bendall RP, Keane FE, Tedder RS, Ijaz S| title=Persistent carriage of hepatitis E virus in patients with HIV infection. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 10 | pages= 1025-7 | pmid=19726781 | doi=10.1056/NEJMc0903778 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19726781  }} </ref>
[[Liver disease]] in some of these patients progresses to [[fibrosis]] and [[cirrhosis]].<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075  }} </ref><ref name="pmid21354150">{{cite journal| author=Kamar N, Garrouste C, Haagsma EB, Garrigue V, Pischke S, Chauvet C et al.| title=Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. | journal=Gastroenterology | year= 2011 | volume= 140 | issue= 5 | pages= 1481-9 | pmid=21354150 | doi=10.1053/j.gastro.2011.02.050 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21354150  }} </ref><ref name="pmid23913727">{{cite journal| author=Grewal P, Kamili S, Motamed D| title=Chronic hepatitis E in an immunocompetent patient: a case report. | journal=Hepatology | year= 2014 | volume= 59 | issue= 1 | pages= 347-8 | pmid=23913727 | doi=10.1002/hep.26636 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23913727  }} </ref>


==Complications==
==Complications==
Common complications of hepatitis E include:
*"Acute-on-chronic disease"
*"Acute-on-chronic disease"
*[[Chronic hepatitis]]
*[[Chronic hepatitis]]
*[[Liver cirrhosis]], which may be diagnosed and monitored by [[ultrasound]] and abdominal [[CT]].
*[[Liver cirrhosis]], which may be diagnosed and monitored by [[ultrasound]] and abdominal [[CT]]
*[[Liver failure]]:
*[[Liver failure]]:
**[[Ascites]]
**[[Ascites]]
===Extra-Hepatic===
===Extra-Hepatic===
Hepatitis E may also present with extra-hepatic manifestations, including:<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075  }} </ref><ref name="pmid22298032">{{cite journal| author=Kamar N, Weclawiak H, Guilbeau-Frugier C, Legrand-Abravanel F, Cointault O, Ribes D et al.| title=Hepatitis E virus and the kidney in solid-organ transplant patients. | journal=Transplantation | year= 2012 | volume= 93 | issue= 6 | pages= 617-23 | pmid=22298032 | doi=10.1097/TP.0b013e318245f14c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22298032  }} </ref><ref name="pmid20346067">{{cite journal| author=Kamar N, Izopet J, Cintas P, Garrouste C, Uro-Coste E, Cointault O et al.| title=Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis. | journal=Am J Transplant | year= 2010 | volume= 10 | issue= 5 | pages= 1321-4 | pmid=20346067 | doi=10.1111/j.1600-6143.2010.03068.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20346067  }} </ref>
Hepatitis E may also present with extra-hepatic manifestations, including:<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075  }} </ref><ref name="pmid22298032">{{cite journal| author=Kamar N, Weclawiak H, Guilbeau-Frugier C, Legrand-Abravanel F, Cointault O, Ribes D et al.| title=Hepatitis E virus and the kidney in solid-organ transplant patients. | journal=Transplantation | year= 2012 | volume= 93 | issue= 6 | pages= 617-23 | pmid=22298032 | doi=10.1097/TP.0b013e318245f14c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22298032  }} </ref><ref name="pmid20346067">{{cite journal| author=Kamar N, Izopet J, Cintas P, Garrouste C, Uro-Coste E, Cointault O et al.| title=Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis. | journal=Am J Transplant | year= 2010 | volume= 10 | issue= 5 | pages= 1321-4 | pmid=20346067 | doi=10.1111/j.1600-6143.2010.03068.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20346067  }} </ref>
*[[Muscle weakness]]
*[[Peripheral neuropathy]]
*[[Peripheral neuropathy]]
*[[Confusion]]
*[[Encephalitis]]
*[[Encephalitis]]  
*Acute transverse [[myelitis]]<ref name="pmid16651680">{{cite journal| author=Mandal K, Chopra N| title=Acute transverse myelitis following hepatitis E virus infection. | journal=Indian Pediatr | year= 2006 | volume= 43 | issue= 4 | pages= 365-6 | pmid=16651680 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16651680  }} </ref>
*Acute [[meningoencephalitis]]<ref name="pmid11723302">{{cite journal| author=Kejariwal D, Roy S, Sarkar N| title=Seizure associated with acute hepatitis E. | journal=Neurology | year= 2001 | volume= 57 | issue= 10 | pages= 1935 | pmid=11723302 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11723302  }} </ref>
*[[Ataxia]]
*[[Ataxia]]
*[[Bell's palsy]]
*[[Bell's palsy]]<ref name="pmid16909746">{{cite journal| author=Dixit VK, Abhilash VB, Kate MP, Jain AK| title=Hepatitis E infection with Bell's palsy. | journal=J Assoc Physicians India | year= 2006 | volume= 54 | issue=  | pages= 418 | pmid=16909746 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16909746  }} </ref>
*[[Guillain-Barré syndrome]]
*[[Guillain-Barré syndrome]]<ref name="pmid23987830">{{cite journal| author=Santos L, Mesquita JR, Rocha Pereira N, Lima-Alves C, Serrão R, Figueiredo P et al.| title=Acute hepatitis E complicated by Guillain-Barre syndrome in Portugal, December 2012--a case report. | journal=Euro Surveill | year= 2013 | volume= 18 | issue= 34 | pages=  | pmid=23987830 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23987830  }} </ref>
*Neuralgic amyotrophy<ref name="pmid24401685">{{cite journal| author=van Eijk JJ, Madden RG, van der Eijk AA, Hunter JG, Reimerink JH, Bendall RP et al.| title=Neuralgic amyotrophy and hepatitis E virus infection. | journal=Neurology | year= 2014 | volume= 82 | issue= 6 | pages= 498-503 | pmid=24401685 | doi=10.1212/WNL.0000000000000112 | pmc=PMC3937863 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24401685  }} </ref>
*[[Radiculopathy|Polyradiculopathy]]
*[[Radiculopathy|Polyradiculopathy]]
*[[Arthritis]]
*[[Arthritis]]
*[[Pancreatitis]]
*Acute [[pancreatitis]]<ref name="pmid21628104">{{cite journal| author=Deniel C, Coton T, Brardjanian S, Guisset M, Nicand E, Simon F| title=Acute pancreatitis: a rare complication of acute hepatitis E. | journal=J Clin Virol | year= 2011 | volume= 51 | issue= 3 | pages= 202-4 | pmid=21628104 | doi=10.1016/j.jcv.2011.04.009 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21628104  }} </ref>
*[[Aplastic anemia]]
*[[Aplastic anemia]]
*Decrease of [[GFR]] (Chronic hepatitis E)
*Decrease of [[GFR]] (Chronic hepatitis E)
*[[Glomerulonephritis]] (Chronic hepatitis E)
*[[Membranoproliferative Glomerulonephritis]]<ref name="pmid22298032">{{cite journal| author=Kamar N, Weclawiak H, Guilbeau-Frugier C, Legrand-Abravanel F, Cointault O, Ribes D et al.| title=Hepatitis E virus and the kidney in solid-organ transplant patients. | journal=Transplantation | year= 2012 | volume= 93 | issue= 6 | pages= 617-23 | pmid=22298032 | doi=10.1097/TP.0b013e318245f14c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22298032  }} </ref>
*[[Membranous glomerulonephritis]]<ref name="pmid22298032">{{cite journal| author=Kamar N, Weclawiak H, Guilbeau-Frugier C, Legrand-Abravanel F, Cointault O, Ribes D et al.| title=Hepatitis E virus and the kidney in solid-organ transplant patients. | journal=Transplantation | year= 2012 | volume= 93 | issue= 6 | pages= 617-23 | pmid=22298032 | doi=10.1097/TP.0b013e318245f14c | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22298032  }} </ref>
*[[Thrombocytopenia]]<ref name="pmid18480231">{{cite journal| author=Colson P, Payraudeau E, Leonnet C, De Montigny S, Villeneuve L, Motte A et al.| title=Severe thrombocytopenia associated with acute hepatitis E virus infection. | journal=J Clin Microbiol | year= 2008 | volume= 46 | issue= 7 | pages= 2450-2 | pmid=18480231 | doi=10.1128/JCM.02295-07 | pmc=PMC2446901 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18480231  }} </ref>
 
===Newborns of Infected Mothers===
Newborns from mothers [[infected]] with [[HEV]] have a [[mortality rate]] of about 50%.<ref name="pmid19228284">{{cite journal| author=Khuroo MS, Kamili S, Khuroo MS| title=Clinical course and duration of viremia in vertically transmitted hepatitis E virus (HEV) infection in babies born to HEV-infected mothers. | journal=J Viral Hepat | year= 2009 | volume= 16 | issue= 7 | pages= 519-23 | pmid=19228284 | doi=10.1111/j.1365-2893.2009.01101.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19228284  }} </ref> These infants may show:<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388  }} </ref>
 
*Icteric hepatitis
 
*Anicteric hepatitis
 
*[[Hyperbilirubinemia]]
 
*[[Prematurity]]
 
*[[Hypothermia]]
 
*[[Hypoglycemia]]


==Prognosis==
==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]].<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046  }} </ref>
Hepatitis E is self-limited in most [[immunocompetent]] patients. For these cases the [[prognosis]] is 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 has poor [[prognosis]].<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046 }} </ref>
 
*The [[mortality rate]] of hospitalized patients with hepatitis E is 0.5 - 4%.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388  }} </ref><ref name="pmid1464145">{{cite journal| author=Naik SR, Aggarwal R, Salunke PN, Mehrotra NN| title=A large waterborne viral hepatitis E epidemic in Kanpur, India. | journal=Bull World Health Organ | year= 1992 | volume= 70 | issue= 5 | pages= 597-604 | pmid=1464145 | doi= | pmc=PMC2393368 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1464145  }} </ref>
 
*In developing countries, [[mortality rate]] during [[epidemics]] is 0.2 - 4.0%.<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046  }} </ref> In these countries, [[mortality rate]] in pregnant women ranges from 10 - 25%, and is often due to fulminant [[hepatic failure]], [[hemorrhage]] or [[eclampsia]].<ref name="pmid8404882">{{cite journal| author=Tsega E, Krawczynski K, Hansson BG, Nordenfelt E| title=Hepatitis E virus infection in pregnancy in Ethiopia. | journal=Ethiop Med J | year= 1993 | volume= 31 | issue= 3 | pages= 173-81 | pmid=8404882 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8404882 }} </ref>


==References==
==References==
{{reflist|2}}
{{reflist|2}}
{{WS}}
{{WH}}


[[Category:Hepatitis|E]]
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[[Category:Up-To-Date]]
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Latest revision as of 22:07, 29 July 2020

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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

Most patients with the acute form of hepatitis E are asymptomatic. Acute hepatitis E progresses according to the following stages: incubation, which usually lasts a mean of 40 days; prodrome or preicteric phase; and symptomatic or icteric phase. The prodromal phase starts with unspecific symptoms, such as fever, weakness, malaise, anorexia, nausea and vomiting, and abdominal pain. The icteric phase usually begins with jaundice, follows the offset of the prodromal symptoms, and may include cholestatic symptoms, such as acholic stools and dark-colored urine. Pregnant women may experience more severe forms of the disease, possibly progressing into hepatic failure. Chronic hepatitis E is commonly found in immunocompromised patients, such as those infected with HIV, undergoing chemotherapy, or with a history of organ transplant. Complications of hepatitis E may include: cirrhosis and liver failure. Extra-hepatic complications may also be noted: peripheral neuropathy; encephalitis; acute transverse myelitis; and Guillain-Barré syndrome. The prognosis of hepatitis E is good in asymptomatic cases, however, immunocompromised patients and pregnant women have higher mortality rates.

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 anicteric hepatitis, or as acute icteric hepatitis. The clinical course of acute hepatitis E progresses according to the following phases:[5][6][7][8][2]

Clinical Course
Stage of Infection Symptoms
Incubation period
Prodromal or Preicteric Phase
  • Lasts for a few days
  • Viremia lasts for few weeks after symptom onset
  • 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

Chronic infection is defined by detection of HEV RNA in blood, or in stool, for more than 6 months. The predominant genotype causing chronic infection is HEV3, as HEV 1 and HEV 2 have not been reported in chronic disease.[5] 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 to fibrosis and cirrhosis.[4][13][16]

Complications

Common complications of hepatitis E include:

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%.[26] These infants may show:[2]

  • Icteric hepatitis
  • Anicteric hepatitis

Prognosis

Hepatitis E is self-limited in most immunocompetent patients. For these cases the prognosis is 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 has poor prognosis.[5]

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 2.5 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 5.3 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. ↑ 17.0 17.1 17.2 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. ↑ Mandal K, Chopra N (2006). "Acute transverse myelitis following hepatitis E virus infection". Indian Pediatr. 43 (4): 365–6. PMID 16651680.
  20. ↑ Kejariwal D, Roy S, Sarkar N (2001). "Seizure associated with acute hepatitis E." Neurology. 57 (10): 1935. PMID 11723302.
  21. ↑ Dixit VK, Abhilash VB, Kate MP, Jain AK (2006). "Hepatitis E infection with Bell's palsy". J Assoc Physicians India. 54: 418. PMID 16909746.
  22. ↑ Santos L, Mesquita JR, Rocha Pereira N, Lima-Alves C, Serrão R, Figueiredo P; et al. (2013). "Acute hepatitis E complicated by Guillain-Barre syndrome in Portugal, December 2012--a case report". Euro Surveill. 18 (34). PMID 23987830.
  23. ↑ van Eijk JJ, Madden RG, van der Eijk AA, Hunter JG, Reimerink JH, Bendall RP; et al. (2014). "Neuralgic amyotrophy and hepatitis E virus infection". Neurology. 82 (6): 498–503. doi:10.1212/WNL.0000000000000112. PMC 3937863. PMID 24401685.
  24. ↑ Deniel C, Coton T, Brardjanian S, Guisset M, Nicand E, Simon F (2011). "Acute pancreatitis: a rare complication of acute hepatitis E." J Clin Virol. 51 (3): 202–4. doi:10.1016/j.jcv.2011.04.009. PMID 21628104.
  25. ↑ Colson P, Payraudeau E, Leonnet C, De Montigny S, Villeneuve L, Motte A; et al. (2008). "Severe thrombocytopenia associated with acute hepatitis E virus infection". J Clin Microbiol. 46 (7): 2450–2. doi:10.1128/JCM.02295-07. PMC 2446901. PMID 18480231.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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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