Hepatitis E

Hepatitis E

• Hepatitis E is a virus (HEV) transmitted in much the same way as hepatitis A virus and it does not often occur in the United States
• HEV is found in the stool of an infected person.
• It is spread when someone unknowingly ingests the virus – even in microscopic amounts.
• In developing countries, people most often get hepatitis E from drinking water contaminated by feces from people who are infected with the virus. In the United States and other developed countries where hepatitis E is not common, people have gotten sick with hepatitis E after eating raw or undercooked pork, venison, wild boar meat, or shellfish.
• In the vast majority of people, HEV infection results in a self-limited, acute illness.
• However, acute infection can become chronic in rare cases, primarily in people who have received solid-organ transplants.

Hepatitis E virus

Incidence

• Hepatitis E is not commonly acquired in the United States; most cases of symptomatic hepatitis E in the United States occur among people who have traveled to a developing country where hepatitis E is endemic.
• Sporadic, non-travel-related cases of hepatitis E have been identified in the United States; no clear exposure was identified for these domestically acquired cases.
• Sporadic cases of hepatitis E in developed countries, including the United States, are primarily caused by HEV genotype 3 and largely affect older men (those >40 years of age).

Risk factors

• Hepatitis E is most common in developing countries with inadequate water supply and poor environmental sanitation.
• Hepatitis E epidemics involving large numbers of people have been reported in Asia, the Middle East, Africa, and Central America.
• People living in crowded camps or temporary housing, including refugees and people who are internally displaced, are at particularly high risk.

Hepatitis E-Virus genotypes

Genotypes

HEV is unique, in that it has a different clinical and epidemiologic profile depending on where the infection is acquired. This can be attributed largely to the viral genotypes circulating in different parts of the world. Four genotypes of HEV cause illness in humans, each displaying different epidemiologic and clinical characteristics in developing and developed countries. Cases of hepatitis E typically present in one of two ways: either as large outbreaks and sporadic cases in areas where HEV is endemic. Genotype 1 in Asia and Africa, Genotype 2 in Mexico and west Africa, (genotype 3 is seen in isolated cases in developed countries like the United States and Genotype 4 in Taiwan and China. Recently, a new genotype genotype 7 was identified in a liver-transplant recipient from UAE with chronic hepatitis E virus infection who frequently consumed camel meat and milk.

Histopathology of acute hepatitis

Transmission and Exposure

• HEV is usually spread by the fecal-oral route.
• In developing countries, where HEV genotypes 1 and 2 predominate, the most common source of HEV infection is contaminated drinking water.
• In developed countries, sporadic cases of HEV genotype 3 have occurred following consumption of uncooked/undercooked pork or deer meat. Consumption of shellfish was a risk factor in a recently described outbreak that occurred among cruise ship passengers.
• HEV genotype 4, detected in China, Taiwan, and Japan, has also been associated with foodborne transmission.

Animal spread

• Hepatitis E can infect certain mammals, and consumption of uncooked/undercooked meat or organs from infected animals can lead to foodborne transmission to humans.
• HEV RNA (genotypes 3 and 4) has been extracted from pork, boar, and deer meat.

Symptoms

When they occur, the signs and symptoms of hepatitis E are similar to those of other types of acute viral hepatitis and liver injury. They include:

• Fever
• Fatigue
• Loss of appetite
• Nausea
• Vomiting
• Abdominal pain
• Jaundice
• Dark urine
• Clay-colored stool
• Joint pain

The ratio of symptomatic to asymptomatic infection ranges from 1:2 to 1:13.

Hepatitis E Virus genome and encoded proteins

Asymptomatic infection

Many people with hepatitis E do not have symptoms of acute infection. In developing countries, symptomatic hepatitis E commonly occurs among older adolescents and young adults (i.e., people aged 15–44 years).

Pregnant women

Pregnant women are more likely to experience severe illness, including fulminant hepatitis and death.

Onset

When symptoms occur, they usually develop 15–60 days (mean: 40 days) after exposure.

Infectivity

The specific period of infectiousness for HEV has not been determined, but virus excretion in stool has been demonstrated from 1 week prior to onset to 30 days after the onset of jaundice (9). Chronically infected persons shed virus as long as they remain infected.

Course

• Most people with hepatitis E recover completely. During hepatitis E outbreaks, the overall case-fatality rate is about 1%.
• However, for pregnant women, hepatitis E can be a serious illness, with mortality reaching 10%–30% among pregnant women in their third trimester. Hepatitis E can also pose serious health threats to people with preexisting chronic liver disease and organ-transplant recipients on immunosuppressive therapy, resulting in decompensated liver disease and death.

To date, there is no report of progression of acute hepatitis E to chronic hepatitis E in developing countries, where HEV genotypes 1 and 2 are the predominant causes of illness.

Diagnosis

HEV infection should be considered in any person with symptoms of viral hepatitis who tests negative for serologic markers of hepatitis A, hepatitis B, hepatitis C, other hepatotropic viruses, and all other causes of acute liver injury. Any symptomatic person who has traveled either to or from an hepatitis E-endemic area or outbreak-afflicted region should also be evaluated for HEV infection.

Treatment

• Hepatitis E usually resolves on its own without treatment. There is no specific antiviral therapy for acute hepatitis E. Physicians should offer supportive therapy.
• Patients are typically advised to rest, get adequate nutrition and fluids, avoid alcohol, and check with their physician before taking any medications that can damage the liver, especially acetaminophen.
• Hospitalization is sometimes required in severe cases and should be considered for pregnant women.
• Few case reports and case series have indicated that modification of immunosuppressive medication and/or use of antiviral drugs may result in spontaneous viral clearance in immunocompromised patients with chronic hepatitis E.

Prevention

• Prevention of hepatitis E relies primarily on good sanitation and the availability of clean drinking water.
• Travelers to developing countries can reduce their risk for infection by not drinking unpurified water.
• Boiling and chlorination of water will inactivate HEV. Avoiding raw pork and venison can reduce the risk of HEV genotype 3 transmission.
• Immune globulin is not effective in preventing hepatitis E.
• No FDA-approved vaccine for hepatitis E is currently available in the United States; however, in 2012 a recombinant vaccine was approved for use in China.

Hepatitis E Resources
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