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.