Hepatitis E

A form of liver disease characterized by inflammation of the liver due to infection with the hepatitis E virus (HEV). Usually a mild disease, hepatitis E but can in rare cases prove fatal, particularly in pregnant women.

HEV is transmitted via food or drink that has been handled by an infected person, or through infected water supplies in areas where fecal matter may get into the water. Consumption of uncooked deer meat is important risk factor for infection with HEV in Japan. Hepatitis E is rare in the US and Canada. It is more common in tropical and subtropical regions of the world.

The finding of anti-HEV antibodies in blood is evidence for prior infection with HEV. There is currently no vaccine or treatment for hepatitis E, although anti-viral drugs may be tried.

Natural History

Hepatitis E disease occur in both sporadic and epidemic forms and is primarily associated with the ingestion of faecally contaminated drinking water. Little secondary household transmission has been documented to occur unlike HAV. Hepatitis E was first documented in New Delhi in 1955 when 29000 cases of icteric hepatitis occurred following the contamination of the city's drinking water. Several other large epidemics have occurred since in the Indian subcontinent and the USSR;

  1. The Delhi Epidemic 1955-56

  2. Ahmedaban, India 1975-76

  3. Pune, India 1978

  4. Kashmir 1980

  5. Tashkent, USSR 1983

These outbreaks were originally thought to be due to HAV but retrospective analysis of stored serum identified HEV as the causative agent. Epidemics have also been reported from parts of China, Africa and Mexico. Sporadic cases predominantly occur in the Indian subcontinent. One notable feature of hepatitis E is the relatively low incidence of clinical disease in case contacts. For example, only 2.4% of household contacts of HE cases developed clinical illness during the 1981-82 epidemic in Kathmandu Valley, whereas the secondary attack rate for HAV was 10 to 20% among household contacts in the same region.

HEV has a slightly longer incubation period than HAV (2-9 weeks, mean = 6 weeks) Like HAV, the disease is usually self-limiting. The clinical attack rate is from 0.7 to 10%. Virus particles are present in the faeces just before the onset of jaundice and the appearance of antibodies. The particles are 27- 30 nm. There is a good animal model available. Various strains of HEV had been isolated in different primates. A particular strain may produce disease in one type of animal but not another. Therefore, different strains appears to have different host susceptibilities. However, cross-protection can be demonstrated between different strains. Therefore, the antigen responsible for producing neutralizing antibodies appears to be the similar.

Clinically, the disease is similar to hepatitis A, but carried a higher mortality, especially amongst pregnant women. HAV has a mortality of 0.1 - 0.2%, in contrast with HEV which carries a mortality of 1-2%. In pregnant women, the case-fatality rate can be as high as 10-20%. The case fatality of HAV for pregnant women is the same as in the general population. The highest attack rate occurred among the 15 - 40 age group. Hepatitis E Accounts for 12-50% of clinical hepatitis in the Indian subcontinent.

Certain questions about the virus remains unanswered, Firstly, why should those aged between 15-40 should be predominantly affected. This implies that infection either occurs sub clinically or not at all in younger individuals. This is supported by a study carried out in Kenya during an investigation of an HEV outbreak among refugees. Also why should the disease carry a higher mortality amongst pregnant women which is not the case with HAV and HBV. The unexpected high mortality rate in HE-infected pregnant women may reflect a unique feature of viral replication and pathogenesis of disease in these women. Indigenous immunoglobulin had been reported to be of use in the prophylaxis against hepatitis E.

Commercial assays are becoming available for the detection of IgG using recombinant antigens and synthetic polypeptides. The sensitivity and specificity of these assays are highly questionable as they tend to give a high seropositive rate eg. there is a seropositive rate of 2% in the US eventhough there had not been any reported cases of hepatitis E in the US. The IgM response is unreliable and is thought to only occur in 50% of patients.

 

Causes and Symptoms

There are at least two strains of HEV, one found in Asia and another in Mexico. The virus may start dividing in the gastrointestinal tract, but it grows mostly in the liver. After an incubation period (the time from when a person is first infected by a virus until the appearance of the earliest symptoms) of two to eight weeks, infected persons develop fever, may feel nauseous, lose their appetite, and often have discomfort or actual pain in the right upper part of the abdomen where the liver is located. Some develop yellowing of the skin and the whites of the eyes (jaundice). Most often the illness is mild and disappears within a few weeks with no lasting effects. Children younger than 14 years and persons over age 50 seldom have jaundice or show other clinical signs of hepatitis. 

Hepatitis E never becomes a chronic (long-lasting) illness, but on rare occasions the acute illness damages and destroys so many liver cells that the liver can no longer function. This is called fulminant liver failure, and may cause death. Pregnant women are at much higher risk of dying from fulminant liver failure; this increased risk is not true of any other type of viral hepatitis. The great majority of patients who recover from acute infection do not continue to carry HEV and cannot pass on the infection to others.

Symptoms of Hepatitis E

Symptoms of hepatitis E do not occur in everyone who has the disease. If they do occur, hepatitis E symptoms usually appear abruptly and go away within a couple of weeks. Symptoms may include:

  • Yellowing of the skin or eyes (also known as jaundice)

  • Feeling very tired

  • Stomach pain (or abdominal pain)

  • Not feeling very hungry

  • Dark urine

  • Pale-colored stool

  • Nausea

  • Diarrhea

  • Muscle pain

  • Joint pain

  • A low-grade fever.

In a number of people, these symptoms may be confused with stomach flu symptoms, especially in the early stages.

Pregnant women (especially those in their third trimester) appear to be exceptionally susceptible to severe disease.

Diagnosis

HEV can be found by microscopically examining a stool sample, but this is not a reliable test, as the virus often dies when stored for a short time. Like other hepatitis viruses, HEV stimulates the body's immune system to produce a substance called an antibody, which can swallow up and destroy the virus. Blood tests can determine elevated antibody levels, which indicate the presence of HEV virus in the body. Unfortunately, such antibody blood tests are not widely available.

Prevention

Most attempts to use blood serum containing HEV antibody to prevent hepatitis in those exposed to HEV have failed. Hopefully, this approach can be made to work so that pregnant women living in endemic areas can be protected. No vaccine is available, though several are being tested. It also is possible that effective anti-viral drugs will be found. The best ways to prevent hepatitis E are to provide safe drinking water and take precautions to use sterilized water and beverages when traveling.

How Is Hepatitis E Spread?

Hepatitis E transmission typically occurs through what is known as "fecal-oral transmission. “If an uninfected person

puts something in the mouth that has been contaminated with the stool of an infected person (even if it looks clean), infection can occur.

Most infections result from contamination of water supplies, such as after monsoon flooding. Unlike hepatitis A (which is also spread through the fecal-oral route), transmission of the hepatitis E virus rarely occurs through contact with a household member or sex partner who has been infected. Casual contact -- as in the usual office, factory, or school setting -- does not spread the virus.

Treatment

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