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With the scarcity of data from efficient animal models, there are still open\u2010ended questions about designing new models to study pathogenesis, types, virology, and evolution of these viruses. With an emphasis on available data and updates, there is still enough information to understand the HEV life cycle, pathogen interaction with the host, and the valuation of the role of vaccine and new anti\u2010HEV therapies. However, the World Health Organization (WHO) and the European Association for the Study of the Liver (EASL) preferred to stress prevention and control measures of HEV infections in animals, zoonotic transmission, and foodborne transmission. It is being reviewed that with current knowledge on HEV and existing prevention tools, there is an excellent room for in\u2010depth information about the virus strains, their replication, pathogenicity, and virulence. The current knowledge set also has gaps regarding standardized and validated diagnostic tools, efficacy and safety of the vaccine, and extrahepatic manifestations specifically in pregnant females, immunocompromised patients, and others. This review highlights the areas for more research exploration, focusing on enlisted research questions based on HEV infection to endorse the need for significant improvement in the current set of knowledge for this public health problem.<\/jats:p>","DOI":"10.1002\/jgh3.12646","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T07:16:34Z","timestamp":1630307794000},"page":"1127-1134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Hepatitis E: Genotypes, strategies to prevent and manage, and the existing knowledge gaps"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2651-5179","authenticated-orcid":false,"given":"Lubna","family":"Kamani","sequence":"first","affiliation":[{"name":"Associate Professor &amp; Director, GI Residency Program, Department of Gastroenterology Liaquat National Hospital and Medical College  Karachi Pakistan"},{"name":"Consultant Aga Khan University Hospital  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4777-7565","authenticated-orcid":false,"given":"Zahra Ali","family":"Padhani","sequence":"additional","affiliation":[{"name":"Health Policy and Management, Manager (Research) Aga Khan University Hospital  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2966-7162","authenticated-orcid":false,"given":"Jai K","family":"Das","sequence":"additional","affiliation":[{"name":"Assistant Professor and Head, Section of Public Health and Epidemiology Aga Khan University Hospital  Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Hepatitis E","author":"World Health Organization","year":"2020"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.86"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000149370"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2107574"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1204512"},{"key":"e_1_2_10_7_1","unstructured":"World Health Organization.Hepatitis E: Fact Sheet. 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