Author(s): Eyasu Teshale

Infectious Agent

Hepatitis E is caused by hepatitis E virus (HEV), a spherical, nonenveloped, single-stranded, single-serotype, RNA virus belonging to the Hepeviridae family. Five HEV genotypes (HEV1–4 and HEV-7) are known to cause human disease. HEV-3 and HEV-4 cause hepatitis E in high-income countries, whereas HEV-1, HEV-2, HEV-4, and HEV-7 are associated with disease in low- and middle-income countries. Globally, HEV-1 is the most prevalent cause of hepatitis E. HEV is relatively stable in the environment but can be inactivated by chlorination or by heating to ≥70°C (≈160°F) for 5 minutes.

Transmission

HEV transmission routes vary by genotype distribution. HEV-1 and HEV-2 are transmitted primarily by the fecal–oral route, mainly through drinking contaminated water. Zoonotic foodborne transmission of HEV-3 is associated with eating uncooked or undercooked meat and offal (including liver), of boar, deer, and pig. Consumption of shellfish was implicated in an outbreak of hepatitis E on a cruise ship. HEV-7 infection has been associated with consumption of camel meat and milk.

Transfusion-related hepatitis E increasingly is reported in Europe. Rare, domestically acquired symptomatic disease has been observed in the United States, but its mode of transmission is generally unknown. Vertical transmission of HEV from people infected during pregnancy to their fetuses is common.

Epidemiology

Every year, ≈20 million HEV infections occur globally; ≈3.3 million cases are symptomatic hepatitis E, and ≈70,000 deaths occur. Large waterborne outbreaks have occurred in Africa, Central America, South and central Asia, and tropical East Asia. Many large outbreaks have occurred among refugees and in people living in camps for displaced persons. Sporadic illness is encountered in outbreak-prone areas, but also in regions not prone to outbreaks (e.g., North and South America, temperate East Asia [including China], Europe, the Middle East).

During hepatitis E outbreaks, clinical attack rates are highest among people aged 15–49 years. In areas endemic for HEV-1, infection in a pregnant person can progress to liver failure and death. Miscarriages and neonatal deaths are common complications of HEV infection during pregnancy. In areas where HEV-3 is prevalent, symptomatic disease occurs most frequently in adults aged >50 years. Among immunosuppressed people, particularly solid organ allograft recipients infected with HEV-3, hepatitis E can progress to chronic infection.

Due to the lack of systematic surveillance for hepatitis E, the incidence and characteristics of hepatitis E cases in the United States are unknown. Despite a lack of data on the risk for travel-associated HEV infections, US travelers are at greatest risk when they visit endemic countries and drink contaminated water. Most travel-associated hepatitis E cases have occurred among travelers returning from the Indian subcontinent. When traveling in countries where HEV-3 is found, eating raw or inadequately cooked boar, deer, or pig meat, or food products derived from any of these, can increase the risk for HEV infection.

Clinical Presentation

The incubation period of HEV infection is 2–9 weeks (mean 6 weeks). The spectrum of illness ranges from asymptomatic to severe disease resulting in fulminant hepatitis and death. For most people, hepatitis E is a mild, self-limited disease. Infection with HEV-3 can progress to chronic infection, whereas infection with other genotypes results only in acute infection.

Signs and symptoms of acute hepatitis E include abdominal pain, anorexia, fever, jaundice, and lethargy, and are indistinguishable from other causes of viral hepatitis. Pregnant people with HEV-1 infection, especially those infected during the third trimester, might present with or progress to fulminant liver failure and death, and are at risk for spontaneous abortion and premature delivery. To date, no evidence shows severe outcomes associated with HEV-3 infection in people who are pregnant.

People with preexisting liver disease might have further hepatic decompensation with HEV superinfection. Recipients of solid organ transplants and people with severe immunosuppression tend to have asymptomatic acute HEV infection, but can develop chronic hepatitis E and progressive liver injury from HEV-3 infection.

Diagnosis

Acute hepatitis E is diagnosed by detecting HEV IgM in serum. Detecting HEV RNA in serum or stool specimens further confirms the serologic diagnosis but seldom is required. Longer-term, serial detection of HEV RNA in serum or stool, regardless of the HEV antibody serostatus, suggests chronic HEV infection. No diagnostic test is approved by the US Food and Drug Administration (FDA) to detect HEV infection. Some commercial laboratories, however, perform both serologic and virologic tests upon request.

The Centers for Disease Control and Prevention (CDC), Division of Viral Hepatitis Diagnostic Reference Laboratory can provide diagnostic support for detecting HEV IgM and IgG in clinical samples by using commercially available kits, and offers a PCR assay for detection of HEV RNA in serum and stool samples. For information on sample handling and shipping to CDC’s Division of Viral Hepatitis Diagnostic Reference Laboratory.

Treatment

Treatment for acute hepatitis E is supportive care. Oral ribavirin has been shown to be effective in the treatment of chronic hepatitis E.

Prevention

No FDA-approved vaccine or immune globulin is available to prevent HEV infection. Travelers should avoid drinking unboiled or unchlorinated water or any beverages containing unboiled water or ice. Travelers should eat only thoroughly cooked food, including seafood, meat, offal, and products derived from these.

CDC website: Hepatitis E