Hepatitis E virus causes acute sporadic and epidemic viral hepatitis. Symptomatic HEV infection is most common in young adults aged 15-40 years and is uncommon in children. Although HEV infection is frequent in children, it is mostly asymptomatic and anicteric.5
The clinical presentation of hepatitis E is comparable to hepatitis A.
Typical signs and symptoms of hepatitis include jaundice, anorexia, hepatomegaly, abdominal pain and tenderness, nausea and vomiting, and fever, although the disease may range in severity from subclinical to fulminant.10, 29
Peak viremia and peak shedding of HEV into the faeces occurs during the incubation period and early acute phase of disease. Detection of HEV antigens in the liver generally parallels viremia and faecal shedding of virus.41, 52
The highest rate of clinically evident disease is typically observed in young to middle-age adults. Lower disease rates in younger age groups may be the result of anicteric or/and subclinical HEV infections.18
The severity of an HEV infection is generally greater than the severity of an HAV infection.41
In general, hepatitis E is a self-limiting viral infection followed by recovery.
Occasionally, a fulminant form of hepatitis develops, with mortality rates ranging between 0.5% - 4.0% of the overall population of patients.
Fulminant hepatitis cases in pregnancy may reach a mortality rate of 20% in the 3rd trimester. Premature deliveries with high infant mortality of up to 33% are also observed.10, 29, 40, 41, 48 The reason for this high mortality is not clear yet. Some of the complications of pregnancy are toxemia with hypertension, proteinuria, edema, and kidney lesions. By directly or indirectly affecting the kidneys, HEV might precipitate eclampsia and lead to increased mortality in pregnant women.6
Coinfection of young children with HEV and HAV may lead to severe forms of disease, including acute liver failure.
Since cases of hepatitis E are not clinically distinguishable from other types of acute viral hepatitis, diagnosis is made by biochemical assessment of liver function (laboratory evaluation of: urine bilirubin and urobilinogen, total and direct serum bilirubin, ALT and AST, alkaline phosphatase, prothrombin time, total protein, albumin, IgG, IgA, IgM, complete blood count). Acute hepatitis E is diagnosed when the presence of IgM anti-HEV is detected.41, 52
Hepatitis E should be suspected in outbreaks of waterborne hepatitis occurring in developing countries, especially if the disease is more severe in pregnant women, or if hepatitis A has been excluded. If laboratory tests are not available, epidemiologic evidence can help in establishing a diagnosis.18
HEV RNA can be detected in acute phase faeces by PCR in approximately 50% of cases. Immune electron microscopy is positive in only about 10% of cases.41
The viral proteins pORF2 and pORF3 have been expressed in various recombinant systems and form the basis for diagnostic tests and vaccine studies. To confirm the results of EIA or ELISA tests, Western blot assays to detect IgM and IgG anti-HEV in serum can be used, along with polymerase chain reaction (PCR) tests for the detection of HEV RNA in serum and stool, immunofluorescent antibody blocking assays to detect antibody to HEV antigen in serum and liver, and immune electron microscopy to visualize viral particles in faeces.9, 18, 19, 22, 30, 36, 41, 48, 52, 55, 56
Host immune response
Viremia in bile and serum and shedding of HEV in faeces reach their peak during the incubation period and keep constant levels in the acute phase of the disease. At the same time, HEV antigens can be detected in the liver.
Virus excretion in stools continues for up to 14 days after onset of illness, then disappears during the recovery phase.
Monkeys infected with human HEV are protected against new challenge with homologous or heterologous strains from Asian and African countries. However, the immunity is incomplete since only the clinical disease seems to be prevented, while the virus is still excreted in stools.38
Click here for: Typical serologic course
Screening of blood donors in central Europe and North America has shown a prevalence of anti-HEV antibodies of 1.4 - 2.5%, in South Africa of 1.4%, in Thailand of 2.8%, in Saudi Arabia of 9.5%, and in Egypt of 24.0%.
HEV infections account for >50% of acute sporadic hepatitis in some high endemic areas.
In monkeys, viral replication apparently causes liver damage. The immune response successfully eliminates viremia and shedding of virus in faeces, while not inducing much damage to the liver. Seroconversion marks the clearing of virus from faeces and blood and is correlated with resolution of disease.54
The low amount of intact HEV particles present in patient stools accounts for the generally lower rate of person-to-person transmission of hepatitis E when compared with that of hepatitis A.10
Species specific HEV has been demonstrated in pigs with the identification of swine HEV. Swine HEV is distinct, but closely related to human HEV strains. While specific-pathogen-free pigs can be experimentally infected with the US-2 strain of human HEV, it is still not known whether swine HEV can infect humans, although it can infect chimpanzees under experimental conditions. Until then, swine HEV raises a potential public health concern for zoonosis and xenozoonosis following xenotransplantation with pig organs.32, 33
Although hepatitis E is not endemic in the US and other developed countries, anti-HEV has been found in a significant proportion, up to 28% in some areas, of healthy individuals in these countries.51 Subclinical infection of humans with swine HEV (possible non-human reservoir of virus) might explain the relatively high prevalence of anti-HEV in healthy individuals in areas where hepatitis E is not endemic.33, 60
Most cases of acute hepatitis E in the US, central and western Europe have been reported among travellers returning from high HEV-endemic areas, although a few have occurred in individuals who have not left their country. It appears, therefore, that some HEV is imported into industrialized countries and some is probably endemic, possibly as a zoonosis.29
The occurrence of sporadic HEV infections in humans may maintain transmission during inter epidemic periods.
There is no evidence for sexual transmission or for transmission by transfusion.4
Here is a list of groups of people who are at risk of contracting HEV:
Typical serologic course
From: Robertson BH and Bradley DW. Enterically transmitted hepatitis. In: Lennette EH, Lennette DA, and Lennette ET, eds. Diagnostic Procedures for Viral, Rickettsial, and Chlamydial Infections, 7th ed. Washington, DC, American Public Health Association, 1995:361-373,45 "Copyright (1995) American Public Health Association", with permission.
Summary of clinical, biochemical, and serologic findings in acute hepatitis E.