Hepatitis E Questions and Answers for Health Professionals

Overview and Statistics

What is hepatitis E?

Hepatitis E is a liver disease caused by the hepatitis E virus (HEV). Although rare in developed countries, hepatitis E is widespread in the developing world. 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 (1).

How common is hepatitis E in the United States?

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 (2); 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).

Where is hepatitis E most common?

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 (3). People living in crowded camps or temporary housing, including refugees and people who are internally displaced, are at particularly high risk.

What are the different genotypes of hepatitis E and where can they be found?

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, and genotype 4 in Taiwan and China) or as isolated cases in developed countries like the United States (genotype 3). 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 (4).

Genotypes of Hepatitis E
Characteristics Genotype 1 Genotype 2 Genotype 3 Genotype 4
Geographic Location Africa and Asia Mexico, West Africa Developed Countries China, Taiwan, Japan
Transmission route Waterborne fecal- oral  person-to-person Waterborne fecal-oral Food-borne Food-borne
Groups at high risk for infection Young Adults Young Adults Older Adults (>40 years) and males,
immuno-compromised persons
Young Adults
Zoonotic transmission No No Yes Yes
Chronic Infection No No Yes No
Occurrence of Outbreaks Common Smaller scale outbreaks Uncommon Uncommon

 

 

Transmission and Exposure

How is the hepatitis E virus spread?

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 (5). HEV genotype 4, detected in China, Taiwan, and Japan, has also been associated with foodborne transmission (6).

Can animals spread the hepatitis E virus to humans?

Yes. 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 (7).

Symptoms

What are the signs and symptoms of hepatitis E?

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.

Who is most likely to have symptomatic HEV 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 are more likely to experience severe illness, including fulminant hepatitis and death (8).

How soon after exposure will symptoms appear?

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

How long does an HEV-infected person remain infectious?

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.

How serious is hepatitis E?

Most people with hepatitis E recover completely. During hepatitis E outbreaks, the overall case-fatality rate is about 1% (10). However, for pregnant women, hepatitis E can be a serious illness, with mortality reaching 10%–30% among pregnant women in their third trimester (12). 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.

Can hepatitis E become chronic?

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. However, increasing numbers of hepatitis E genotype 3 infections acquired in developed countries are progressing to cause chronic hepatitis and chronic liver disease. These chronic cases occur mainly among solid-organ transplant recipients receiving immunosuppressive treatment.

Diagnosis and Treatment

Who should be tested for hepatitis E?

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. A detailed history regarding travel, sources of drinking water, uncooked food, and contact with jaundiced persons should be obtained from these patients to aid in diagnosis. Because domestically acquired cases of hepatitis E are occurring in the United States, HEV infection also should be considered in any person with unexplained symptoms of liver injury, regardless of travel history.

How is hepatitis E diagnosed?

Because cases of hepatitis E are not clinically distinguishable from other types of acute viral hepatitis, diagnosis can be confirmed only by testing for the presence of antibody against HEV or HEV RNA. Both serologic and nucleic acid tests are commercially available, but they have not been approved by the U.S. Food and Drug Administration (FDA) for use in the United States. These tests are used for research purposes, but some commercial laboratories use commercially available assays from other countries.

Where can I learn more about hepatitis E serology?

CDC offers an online training that covers the serology of hepatitis E and other types of viral hepatitis.

How is hepatitis E treated?

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

How is hepatitis E prevented?

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.

Is there a vaccine for 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.

References

1. Marion O, Abravanel F, Lhomme S, Izopet J, Kamar N. Hepatitis E in transplantation. Curr Infect Dis Rep 2016;18(3):8.
2. Tohme RA, Drobeniuc J, Sanchez R, et al. Acute hepatitis associated with autochthonous hepatitis E virus infection–San Antonio, Texas, 2009. Clin Infect Dis 2011 Oct;53(8):793-6.
3. Teshale EH, Hu DJ. Hepatitis E: epidemiology and prevention. World J Hepatol 2011;Dec 27;3(12):285-91.
4. Lee GH, Tan BH, Teo EC, et al. Chronic infection with Camelid Hepatitis E virus in a liver transplant recipient who regularly consumes camel meat and milk. Gastroenterology. 2016; 150(2):355-7.
5. Said B, Ijaz S, Kafatos G, et al. Hepatitis E outbreak on cruise ship. Emerg Infect Dis 2009;15(11):1738-44.
6. Kanayama A, Arima Y, Yamagishi T, et al. Epidemiology of domestically acquired hepatitis E virus infection in Japan: assessment of the nationally reported surveillance data, 2007-2013. J Med Microbiol 2015;64(7):752-8.
7. Feagins AR, Opriessnig T, Guenette DK, Halbur PG, Meng XJ. Detection and characterization of infectious Hepatitis E virus from commercial pig livers sold in local grocery stores in the USA. J Gen Virol 2007;88(Pt 3):912-7.
8. Kumar A, Beniwal M, Kar P, Sharma JB, Murthy NS. Hepatitis E in pregnancy. Int J Gynaecol Obstet 2004;85(3):240-4.
9. McCaustland KA, Krawczynski K, Ebert JW, et al. Hepatitis E virus infection in chimpanzees: a retrospective analysis. Arch Virol 2000;145(9):1909-18.
10. Teshale EH, Hu DJ, Holmberg SD. The two faces of hepatitis E virus. Clin Infect Dis 2010;51(3):328-34.
11. Patra S, Kumar A, Trivedi SS, Puri M, Sarin SK. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med 2007;147(1):28-33.