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Hepatitis E

By Anna E. Rutherford, MD, MPH, Assistant Professor of Medicine; Clinical Director of Hepatology, Harvard Medical School; Brigham and Women’s Hospital

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Hepatitis E is caused by an enterically transmitted RNA virus and causes typical symptoms of viral hepatitis, including anorexia, malaise, and jaundice. Fulminant hepatitis and death are rare, except during pregnancy. Diagnosis is by antibody testing. Treatment is supportive.

There are 4 genotypes of hepatitis E virus (HEV). All can cause acute viral hepatitis.

Genotypes 1 and 2 usually cause waterborne outbreaks that are linked to fecal contamination of the water supply and fecal-oral person-to-person transmission. Outbreaks have occurred in China, India, Mexico, Pakistan, Peru, Russia, and central and northern Africa. These outbreaks have epidemiologic characteristics similar to hepatitis A virus epidemics. Sporadic cases also occur. No outbreaks have occurred in the US or in Western Europe. Most cases in the developed world occur in travelers returning from a developing country, but sporadic cases not associated with travel have been reported.

Genotypes 3 and 4 typically cause sporadic cases rather than outbreaks. Transmission is food-borne and can involve eating uncooked or undercooked meat; cases have been associated with consumption of pork, deer, and shellfish.

HEV was not originally thought to cause chronic hepatitis, cirrhosis, or chronic carrier state; however, reports document chronic genotype 3 hepatitis E exclusively in immunocompromised patients (including organ-transplant recipients, patients receiving cancer chemotherapy, and HIV-infected patients).

Symptoms and Signs

Typical manifestations of viral hepatitis occur: anorexia, malaise, nausea and vomiting, and fever, followed by jaundice.

Hepatitis E may be severe, especially in pregnant women; in them, risk of fulminant hepatitis and death is increased.


  • IgM antibody test (when available)

In the initial diagnosis of acute hepatitis, viral hepatitis should be differentiated from other disorders causing jaundice (see Figure: Simplified diagnostic approach to possible acute viral hepatitis.). If acute viral hepatitis is suspected, the following tests are done to screen for hepatitis viruses A, B, and C:

  • IgM antibody to hepatitis A virus (IgM anti-HAV)

  • Hepatitis B surface antigen (HBsAg)

  • IgM antibody to hepatitis B core (IgM anti-HBc)

  • Antibody to hepatitis C virus (anti-HCV) and hepatitis C RNA (HCV-RNA) PCR

If tests for hepatitis A, B, and C are negative but the patient has typical manifestations of viral hepatitis and has recently traveled to an endemic area, IgM antibody to HEV (IgM anti-HEV) should be measured if the test is available.


  • Supportive care

  • For chronic hepatitis E, possibly ribavirin

No treatments attenuate acute viral hepatitis, including hepatitis E.

Preliminary studies suggest antiviral efficacy for ribavirin in treatment of chronic hepatitis E.

Alcohol should be avoided because it can increase liver damage. Restrictions on diet or activity, including commonly prescribed bed rest, have no scientific basis.

Most patients may safely return to work after jaundice resolves, even if AST or ALT levels are slightly elevated.

For cholestatic hepatitis, cholestyramine 8 g po once/day or bid can relieve itching.

Viral hepatitis should be reported to the local or state health department.


Good personal hygiene and standard universal precautions help prevent fecal-oral transmission of hepatitis E. Boiling water appears to reduce risk of infection. Because person-to-person transmission is rare, isolation of infected patients is not indicated.

A vaccine for hepatitis E is now available in China; it is not available in the US. The vaccine appears to have about 95% efficacy in preventing symptomatic infection in males and is safe. Efficacy in other groups, duration of protection, and efficacy in preventing asymptomatic infection are unknown.

Key Points

  • Transmission of hepatitis E is usually by the fecal-oral route.

  • Most patients recover spontaneously, but pregnant women have an increased risk of fulminant hepatitis and death.

  • Genotype 3 may cause chronic hepatitis in immunocompromised patients.

  • Suspect hepatitis E in travelers to endemic regions; do IgM anti-HEV testing if available.

  • Treat patients supportively; consider using ribavirin for chronic hepatitis E.

  • A vaccine is available in China.

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