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World J Hepatol. Dec 27, 2021; 13(12): 1875-1891
Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.1875
Genotype E: The neglected genotype of hepatitis B virus
Luicer Anne Olubayo Ingasia, Constance Wose Kinge, Anna Kramvis
Luicer Anne Olubayo Ingasia, Constance Wose Kinge, Anna Kramvis, Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, Gauteng, South Africa
Constance Wose Kinge, Department of Implementation Science, Right to Care, Johannesburg 0046, Gauteng, South Africa
Author contributions: Ingasia LAO performed the literature search and wrote the paper; Wose Kinge C supervised the student; Kramvis A conceptualized the research and supervised the student; all authors read and approved the final manuscript.
Supported by National Research Foundation (NRF) of South Africa, No. GUN #93516; Deutsche Forschungsgemeinschaft (DFG; English: German Research Foundation); and Cancer Association of South Africa (CANSA).
Conflict-of-interest statement: The authors declare that there is no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Anna Kramvis, BSc, PhD, Director, Professor, Hepatitis Virus Diversity Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, Gauteng, South Africa. anna.kramvis@wits.ac.za
Received: May 7, 2021
Peer-review started: May 7, 2021
First decision: June 4, 2021
Revised: June 15, 2021
Accepted: November 15, 2021
Article in press: November 15, 2021
Published online: December 27, 2021
Processing time: 233 Days and 16.4 Hours
Abstract

Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge status and gaps in its origin and evolution, natural history of infection, disease progression, response to antiviral therapy and vaccination are discussed. Genotype E is an African genotype, with unique molecular characteristics that is found mainly in Western and Central Africa and rarely outside Africa except in individuals of African descent. The low prevalence of this genotype in the African descendant populations in the New World, phylogeographic analyses, the low genetic diversity and evidence of remnants of genotype E in ancient HBV samples suggests the relatively recent re-introduction into the population. There is scarcity of information on the clinical and virological characteristics of genotype E-infected patients, disease progression and outcomes and efficacy of anti-HBV drugs. Individuals infected with genotype E have been characterised with high hepatitis B e antigen-positivity and high viral load with a lower end of treatment response to interferon-alpha. A minority of genotype E-infected participants have been included in studies in which treatment response was monitored. Of concern is that current guidelines do not consider patients infected with genotype E. Thus, there is an urgent need for further large-scale investigations into genotype E, the neglected genotype of HBV.

Keywords: Hepatitis B virus; Genotype E; Evolution; Clinical significance; Antiviral therapy; Vaccination

Core Tip: Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge status and gaps in its origin and evolution, natural history of infection, disease progression, response to antiviral therapy and vaccination discussed in this review highlight the urgent need for further more in-depth and large-scale investigations into genotype E, the neglected genotype of hepatitis B virus.