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]Kmush BL, Labrique AB, Dalton HR, et al. Two generations of "Gold Standards": the Impact of a decade in hepatitis E virus testing innovation on population seroprevalence. Am J Trop Med Hyg. 2015 Oct;93(4):714-7.
https://www.ajtmh.org/view/journals/tpmd/93/4/article-p714.xml
http://www.ncbi.nlm.nih.gov/pubmed/26149865?tool=bestpractice.com
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]European Association for the Study of the Liver. EASL clinical practice guidelines on hepatitis E virus infection. J Hepatol. 2018 Jun;68(6):1256-71.
https://www.journal-of-hepatology.eu/article/S0168-8278(18)30155-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29609832?tool=bestpractice.com
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]European Association for the Study of the Liver. EASL clinical practice guidelines on hepatitis E virus infection. J Hepatol. 2018 Jun;68(6):1256-71.
https://www.journal-of-hepatology.eu/article/S0168-8278(18)30155-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29609832?tool=bestpractice.com
[3]Lhomme S, Marion O, Abravanel F, et al. Clinical manifestations, pathogenesis and treatment of hepatitis E virus infections. J Clin Med. 2020 Jan 24;9(2):331.
https://www.mdpi.com/2077-0383/9/2/331
http://www.ncbi.nlm.nih.gov/pubmed/31991629?tool=bestpractice.com
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]World Health Organization. Fact sheets: hepatitis E. Jul 2023 [internet publication].
https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-e
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]Centers for Disease Control and Prevention. Viral hepatitis: hepatitis E. Jun 2020 [internet publication].
https://www.cdc.gov/hepatitis/hev/index.htm
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]Li P, Liu J, Li Y, et al. The global epidemiology of hepatitis E virus infection: a systematic review and meta-analysis. Liver Int. 2020 Jul;40(7):1516-28.
https://onlinelibrary.wiley.com/doi/10.1111/liv.14468
http://www.ncbi.nlm.nih.gov/pubmed/32281721?tool=bestpractice.com
In 2015 there were 44,000 deaths resulting from HEV infection.[15]World Health Organization. Fact sheets: hepatitis E. Jul 2023 [internet publication].
https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-e
The highest prevalence of HEV is in Africa and Asia, particularly in developing countries with poor sanitation and inadequate water supply.[1]Centers for Disease Control and Prevention. Viral hepatitis: hepatitis E. Jun 2020 [internet publication].
https://www.cdc.gov/hepatitis/hev/index.htm
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]Centers for Disease Control and Prevention. Viral hepatitis: hepatitis E. Jun 2020 [internet publication].
https://www.cdc.gov/hepatitis/hev/index.htm
[2]European Association for the Study of the Liver. EASL clinical practice guidelines on hepatitis E virus infection. J Hepatol. 2018 Jun;68(6):1256-71.
https://www.journal-of-hepatology.eu/article/S0168-8278(18)30155-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29609832?tool=bestpractice.com
[17]Kamar N, Bendall R, Legrand-Abravanel F, et al. Hepatitis E. Lancet. 2012 Jun 30;379(9835):2477-88.
http://www.ncbi.nlm.nih.gov/pubmed/22549046?tool=bestpractice.com
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]Centers for Disease Control and Prevention. Viral hepatitis: hepatitis E. Jun 2020 [internet publication].
https://www.cdc.gov/hepatitis/hev/index.htm
[18]Oeser C, Vaughan A, Said B, et al. Epidemiology of hepatitis E in England and Wales: a 10-year retrospective surveillance study, 2008-2017. J Infect Dis. 2019 Jul 31;220(5):802-10.
https://academic.oup.com/jid/article/220/5/802/5479512
http://www.ncbi.nlm.nih.gov/pubmed/31107958?tool=bestpractice.com
Infection caused by genotype 4 is most commonly found in China, Japan, and Taiwan.[1]Centers for Disease Control and Prevention. Viral hepatitis: hepatitis E. Jun 2020 [internet publication].
https://www.cdc.gov/hepatitis/hev/index.htm
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]Centers for Disease Control and Prevention. Viral hepatitis: hepatitis E. Jun 2020 [internet publication].
https://www.cdc.gov/hepatitis/hev/index.htm
[19]Meng XJ, Wiseman B, Elvinger F, et al. Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries. J Clin Microbiol. 2002 Jan;40(1):117-22.
https://journals.asm.org/doi/10.1128/jcm.40.1.117-122.2002
http://www.ncbi.nlm.nih.gov/pubmed/11773103?tool=bestpractice.com
Infection with genotypes 3 and 4 HEV is not associated with increased risk of severe illness or excess mortality in pregnant patients.[2]European Association for the Study of the Liver. EASL clinical practice guidelines on hepatitis E virus infection. J Hepatol. 2018 Jun;68(6):1256-71.
https://www.journal-of-hepatology.eu/article/S0168-8278(18)30155-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29609832?tool=bestpractice.com
Hepatitis E is not common in the US, and most HEV infection is acquired through travel to an endemic country.[1]Centers for Disease Control and Prevention. Viral hepatitis: hepatitis E. Jun 2020 [internet publication].
https://www.cdc.gov/hepatitis/hev/index.htm
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]Teshale EH, Denniston MM, Drobeniuc J, et al. Decline in hepatitis E virus antibody prevalence in the United States from 1988-1994 to 2009-2010. J Infect Dis. 2015 Feb 1;211(3):366-73.
https://academic.oup.com/jid/article/211/3/366/2912187
http://www.ncbi.nlm.nih.gov/pubmed/25147277?tool=bestpractice.com
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]Adlhoch C, Avellon A, Baylis SA, et al. Hepatitis E virus: assessment of the epidemiological situation in humans in Europe, 2014/15. J Clin Virol. 2016 Sep;82:9-16.
https://www.sciencedirect.com/science/article/pii/S1386653216301433
http://www.ncbi.nlm.nih.gov/pubmed/27393938?tool=bestpractice.com
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]Adlhoch C, Avellon A, Baylis SA, et al. Hepatitis E virus: assessment of the epidemiological situation in humans in Europe, 2014/15. J Clin Virol. 2016 Sep;82:9-16.
https://www.sciencedirect.com/science/article/pii/S1386653216301433
http://www.ncbi.nlm.nih.gov/pubmed/27393938?tool=bestpractice.com
[22]Hewitt PE, Ijaz S, Brailsford SR, et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet. 2014 Nov 15;384(9956):1766-73.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61034-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25078306?tool=bestpractice.com
[23]Bura M, Łagiedo M, Michalak M, et al. Hepatitis E virus IgG seroprevalence in HIV patients and blood donors, west-central Poland. Int J Infect Dis. 2017 Aug;61:20-2.
https://www.ijidonline.com/article/S1201-9712(17)30150-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/28576599?tool=bestpractice.com
Locally acquired HEV is now the most common cause of acute viral hepatitis in many European countries.[2]European Association for the Study of the Liver. EASL clinical practice guidelines on hepatitis E virus infection. J Hepatol. 2018 Jun;68(6):1256-71.
https://www.journal-of-hepatology.eu/article/S0168-8278(18)30155-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29609832?tool=bestpractice.com
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]Ijaz S, Vyse AJ, Morgan D, et al. Indigenous hepatitis E virus infection in England: more common than it seems. J Clin Virol. 2009 Apr;44(4):272-6.
http://www.ncbi.nlm.nih.gov/pubmed/19217345?tool=bestpractice.com
[25]British Transplantation Society. Guidelines for hepatitis E and solid organ transplantation. First edition. Apr 2017 [internet publication].
https://bts.org.uk/wp-content/uploads/2017/06/BTS_HEV_Guideline-FINAL.pdf