Epidemiology

​The worldwide burden of HEV infection is likely to be underestimated due to several factors, including limitations of data in studies due to poor sensitivity of older serological assays used to estimate seroprevalence.[14]​ These studies also focused on developing countries, where the faecal-oral route of transmission predominates, and not on developed countries, where zoonotic infection is endemic.[2] The improvement in living conditions in many parts of the world and migration patterns has changed the primary route of transmission from faecal-oral to zoonotic.

HEV infection, although the most common cause of acute viral hepatitis globally, results in asymptomatic infection in the majority (possibly over up to 95%) of affected people.[2][3]​​​​ Data from the World Health Organization suggest that worldwide there are 20 million HEV infections annually, resulting in around 3.3 million symptomatic cases.[15]​ Symptomatic infection in adults in developing countries is most common in those aged 44 years and younger; in these regions, infection is usually acquired via the faeco-oral route.[1] A systematic review of data from 75 countries estimated that 12.4% of the global population (approximately 939 million individuals) has had past HEV infection, based on the presence of serum anti-HEV immunoglobulin G (IgG) antibodies.[16]

In 2015 there were 44,000 deaths resulting from HEV infection.[15] The highest prevalence of HEV is in Africa and Asia, particularly in developing countries with poor sanitation and inadequate water supply.[1]

HEV infection has a varying clinical and epidemiological profile depending on the location where infection is acquired. Infection with HEV genotypes 1 and 2 is typically acquired by drinking faecally contaminated water in endemic areas such as Africa and Asia (genotype 1), or Mexico and West Africa (genotype 2). HEV infection acquired via the faeco-oral route is associated with high morbidity and mortality in pregnant patients.[1][2][17]​​​​​ In developed countries, including the US and the UK, sporadic, non-travel-associated cases of HEV infection are primarily caused by HEV genotype 3 and largely affect men >40 years of age and immunocompromised people.[1][18]​​​ Infection caused by genotype 4 is most commonly found in China, Japan, and Taiwan.[1] Genotype 3 and genotype 4 infections are most commonly acquired by ingestion of undercooked or uncooked meat (e.g., pork, wild boar, or deer) but can also be contracted via close association with the animal reservoir, such as by farm workers or veterinarians.[1][19]​​ Infection with genotypes 3 and 4 HEV is not associated with increased risk of severe illness or excess mortality in pregnant patients.[2]

Hepatitis E is not common in the US, and most HEV infection is acquired through travel to an endemic country.[1] In the US, the National Health and Nutrition Examination Survey (1988-1994) demonstrated a seroprevalence of HEV antibody of 21%, but this had declined significantly by 2009-2010; reasons for the decline are unclear.[20]

In parts of Europe, however, confirmed infection rates have increased, with cases of acute HEV infection outnumbering cases of acute hepatitis A and hepatitis B virus infection, although this may be related to testing strategies.[21]​ Based on seroprevalence and blood donor data, it is estimated that there are at least 2 million locally acquired HEV infections in Europe occurring annually.[21][22][23]​​​​​ Locally acquired HEV is now the most common cause of acute viral hepatitis in many European countries.[2] Seroprevalence rates in the general population of England are estimated to be around 13%, suggesting that 200,000 annual infections occur per year, accounting for approximately 600-800 cases of hepatitis.[24][25]​​​

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