Enterically transmitted hepatitis, caused by hepatitis A virus (HAV) and hepatitis E virus (HEV), constitutes a major global public health burden driven by inadequate water and sanitation infrastructure, particularly in low- and middle-income countries. Despite sharing fecal-oral transmission routes, these two infections differ substantially in virology, epidemiology, clinical course, and outcome. HAV, a Picornaviridae member, invariably causes self-limiting acute hepatitis, with effective inactivated vaccines providing lifelong protection. HEV, classified within the Hepeviridae family, presents a more heterogeneous disease profile: epidemic strains (genotypes 1 and 2) cause large waterborne outbreaks in endemic regions and impose disproportionate mortality — up to 30% — in pregnant women, while zoonotic genotypes (3 and 4) circulate endemically in high-income countries and cause chronic hepatitis in immunocompromised patients, a complication absent in HAV infection. This review critically examines the virological characteristics, global and regional epidemiological trends, immunopathogenic mechanisms, clinical manifestations including high-risk populations, diagnostic advances, and current management strategies for both infections. Special attention is given to recent developments from 2019 to 2025, including updated WHO guidance, molecular epidemiology data, the expanding clinical phenotype of chronic HEV, and the unresolved issue of global HEV vaccine access. Significant gaps persist in HEV diagnostic standardization, equitable vaccine deployment, and antiviral development, which constitute priority areas for future research and policy.

Hepatitis A virus, hepatitis E virus, enterically transmitted hepatitis

World Health Organization. Global Hepatitis Report 2024: Action for Access in Low- and Middle-Income Countries. Geneva: WHO; 2024. ISBN: 978-92-4-008398-9.

Shin EC, Jeong SH. Natural history, clinical manifestations, and pathogenesis of hepatitis A. Cold Spring Harb Perspect Med. 2018;8(9):a031708. doi:10.1101/cshperspect.a031708

Heymann DL, ed. Control of Communicable Diseases Manual. 21st ed. Washington DC: APHA Press; 2022. [HAV chapter updated 2022]

Centers for Disease Control and Prevention. Hepatitis A surveillance — United States, 2021. MMWR Morb Mortal Wkly Rep. 2023;72(5):99–105. doi:10.15585/mmwr.mm7205a3

World Health Organization. Hepatitis E Fact Sheet. Updated July 2022. Geneva: WHO; 2022. Available at: https://www.who.int/news-room/fact-sheets/detail/hepatitis-e

Nimgaonkar I, Ding Q, Schwartz RE, Ploss A. Hepatitis E virus: advances and challenges. Nat Rev Gastroenterol Hepatol. 2018;15(2):96–110. doi:10.1038/nrgastro.2017.150

Kamar N, Izopet J, Pavio N, et al. Hepatitis E virus infection. Nat Rev Dis Primers. 2017;3:17086. doi:10.1038/nrdp.2017.86

Kumar A, Beniwal M, Kar P, Sharma JB, Murthy NS. Hepatitis E in pregnancy. Int J Gynaecol Obstet. 2004;85(3):240–244. doi:10.1016/j.ijgo.2003.11.018 [Updated evidence reviewed in: J Hepatol. 2021;74(5):1111–1120. doi:10.1016/j.jhep.2020.11.048]

Spina A, Lenglet A, Beversluis D, et al. A large outbreak of hepatitis E virus genotype 1 infection in an urban setting in Chad likely linked to chronic low-level transmission. PLoS One. 2017;12(5):e0177231. doi:10.1371/journal.pone.0177231

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;82:9–16. doi:10.1016/j.jcv.2016.06.010

Cuthbert JA. Hepatitis A: old and new. Clin Microbiol Rev. 2001;14(1):38–58. doi:10.1128/CMR.14.1.38-58.2001 [Supplemented by: J Hepatol. 2022;77(3):879–892. doi:10.1016/j.jhep.2022.03.006]

Nan Y, Wu C, Zhao Q, Sun Y, Zhang YJ, Zhou EM. Vaccine development against zoonotic hepatitis E virus: open questions and remaining challenges. Front Microbiol. 2018;9:266. doi:10.3389/fmicb.2018.00266

van Eijk JJJ, Madden RG, van der Eijk AA, et al. Neuralgic amyotrophy and hepatitis E virus infection. Neurology. 2017;89(9):909–917. doi:10.1212/WNL.0000000000004314

European Association for the Study of the Liver. EASL Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol. 2018;68(6):1256–1271. doi:10.1016/j.jhep.2018.03.005

Rein DB, Stevens GA, Theaker J, Wittenborn JS, Wiersma ST. The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology. 2012;55(4):988–997. doi:10.1002/hep.25505

World Health Organization. An Advisory Committee on Vaccine Safety: Hepatitis E vaccine recommendations. Wkly Epidemiol Rec. 2015;90(18):185–200.

Pischke S, Behrendt P, Bock CT, Jilg W, Manns MP, Wedemeyer H. Hepatitis E in Germany — an under-reported infectious disease. Dtsch Arztebl Int. 2014;111(35–36):577–583. doi:10.3238/arztebl.2014.0577

Debing Y, Neyts J, Depla E, Vandenberghe J, Maes P. Hepatitis E virus disease and the search for novel therapies. J Hepatol. 2014;61(6):1369–1378. doi:10.1016/j.jhep.2014.08.002

Hartl J, Otto B, Madden RG, et al. Hepatitis E seroprevalence in Europe: a meta-analysis. Viruses. 2016;8(8):211. doi:10.3390/v8080211