Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2020; 26(37): 5543-5560
Published online Oct 7, 2020. doi: 10.3748/wjg.v26.i37.5543
Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment
Abdullah Tarık Aslan, Hatice Yasemin Balaban
Abdullah Tarık Aslan, Department of Internal Medicine, Gölhisar State Hospital, Burdur 15100, Turkey
Hatice Yasemin Balaban, Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara 06100, Turkey
Author contributions: Aslan AT wrote the paper and collected data; Balaban HY carried out data collection; Both authors read and approved the final manuscript.
Conflict-of-interest statement: All authors have no conflicts of interest to be stated.
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:
Corresponding author: Hatice Yasemin Balaban, MD, Professor, Department of Gastroenterology, Hacettepe University Faculty of Medicine, Hacettepe University Sihhiye Campus, Ankara 06100, Turkey.
Received: June 28, 2020
Peer-review started: June 28, 2020
First decision: July 28, 2020
Revised: August 11, 2020
Accepted: September 10, 2020
Article in press: September 10, 2020
Published online: October 7, 2020

The hepatitis E virus (HEV) is the fifth known form of viral hepatitis and was first recognized as the cause of an epidemic of unexplained acute hepatitis in the early 1980s. Globally, it is one of the most frequent causes of acute viral hepatitis. The majority of HEV infections are asymptomatic and lead to the spontaneous clearance of the virus. Among the eight different genotypes identified to date, HEV genotype 1 (HEV1), HEV2, HEV3, and HEV4 are the most frequent genotypes causing infections in humans. HEV1 and HEV2 are prevalent in developing regions and able to result in large-scale outbreaks originating from contaminated water supplies. They are also responsible for severe hepatitis in pregnant patients and infants. In contrast, HEV3 and HEV4 are zoonotic, and the transmission of these genotypes to humans occurs mainly through the fecal contamination of water and consumption of contaminated meat from infected animals. Their main reservoir is the pig, and they are mostly encountered in developed countries. The major risk groups for HEV infection and its ensuing adverse consequences are pregnant women, infants, older people, immunocompromised individuals, patients with underlying chronic liver diseases, and workers that come into close contact with HEV-infected animals. In the clinical perspective, HEV infections have diverse clinical manifestations including acute and self-limiting hepatitis, acute-on-chronic liver disease, chronic hepatitis, cirrhosis, and liver failure. Although HEV mainly results in acute self-limiting infection, chronic HEV infection may occur among immunocompromised patients (e.g., solid-organ transplant recipients). Additionally, HEV-associated extrahepatic manifestations involving various organs have been reported in the last decade, although the causal link for many of them still needs to be proven. Ribavirin and interferon-alpha are the most widely used agents for the treatment of HEV infections with a certain level of success. However, ribavirin is contraindicated in pregnant patients, and interferon-alpha cannot be used in most transplant recipients. Therefore, there is an urgent need for novel antiviral compounds that are safe and effective particularly for patients having contraindications for ribavirin or interferon-alpha and infected by the ribavirin-resistant HEV. In this review article, a literature search using PubMed and MEDLINE databases was performed, up to March 2020. Only the articles published in English were reviewed.

Keywords: Hepatitis E, Hepatitis E virus, Extrahepatic manifestations, Zoonotic infection, Chronic hepatitis, Acute hepatitis

Core Tip: The hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. To date, four main genotypes of the HEV infecting humans have been described. While HEV1 and HEV2 cause only acute hepatitis, HEV3 or HEV4 can become chronic in immunocompromised patients. Extrahepatic manifestations have also been defined for these genotypes. Acute infections are generally self-limiting and do not require special treatment. For chronic hepatitis, ribavirin is the drug of choice. Nevertheless, novel drugs are required for patients in whom ribavirin treatment fails. We herein reviewed the epidemiology, diagnosis, clinical manifestations, and treatment of HEV infections.