The incubation period of HEV infection ranges from 3-8 weeks. It generally has a short prodromal phase and a symptomatic period, which is usually associated with jaundice, lasting several days to weeks. Acute HEV infection is usually self-limited, although fulminant hepatitis can develop. Case fatality averages 5% but ranges between 0-10%.^[1] Chronic HEV infection does not usually develop after acute HEV infection, except rarely in immunosuppressed individuals (see below). The clinical signs and symptoms in patients with typical HEV infection are similar to those seen with other forms of acute viral hepatitis and jaundice is usually accompanied by malaise, anorexia, nausea, vomiting, abdominal pain, fever and hepatomegaly. Laboratory findings include elevated serum concentrations of bilirubin, as well as alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Resolution of the abnormal biochemical tests generally occurs within 1 to 6 weeks after the onset of the illness.

HEV infection tends to be more severe than hepatitis A virus infection and prolonged cholestasis has been described in up to 60% of patients.^[22] An association between HEV infection and Guillain-Barré syndrome has also been reported^[23] as well as a number of other neurological manifestations including Bell’s palsy, peripheral neuropathy, ataxia and confusion.^[24]

A striking feature of HEV infection is that, for reasons that are not fully understood, fulminant hepatic failure occurs more frequently during pregnancy, resulting in a mortality rate of 15-25%, primarily in women in the third trimester.^[25] This high rate may be at least partly due to increased viral replication.^[26] Pregnant women with jaundice and acute viral hepatitis caused by HEV infection also appear to have worse obstetric and foetal outcomes compared to pregnant women who have jaundice and acute viral hepatitis due to other causes.^[27]

Infection with HEV can also lead to hepatic decompensation in patients with pre-existing liver disease and those who are malnourished, a phenomenon called ‘acute-on-chronic liver failure’.^[28]

The differential diagnosis of acute HEV infection mainly includes other forms of acute hepatitis including viral hepatitis due to other hepatitis viruses as well as herpesviruses such as herpes simplex virus, cytomegalovirus and Epstein-Barr virus; drug induced liver disease; ischaemic hepatitis; autoimmune hepatitis and other infectious diseases, such as leptospirosis, dengue, malaria and typhoid.

The basis of acute HEV infection management is supportive, as the disease appears to be self-limiting in non-immunocompromised patients The exception is chronic HEV in immunocompromised individuals as detailed below.