Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment

Abstract

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: Acute hepatitis; Chronic hepatitis; Extrahepatic manifestations; Hepatitis E; Hepatitis E virus; Zoonotic infection.

Figure 1

Diagnostic algorithm of hepatitis E virus infection. For diagnosis of acute hepatitis E virus (HEV) infection in immunocompetent patients, both serologic assays and nucleic acid amplification tests (PCR) should be used in combination. Negative PCR results can be seen in early period of acute infection. On the other hand, serologic tests are not reliable tools in immunosuppressed patients. Therefore, PCR results are much more important in diagnosis of acute infection among these patients. In addition, HEV RNA positivity that is lasting at least 3 mo is accepted as a diagnostic marker for chronic HEV infection in some immunocompromised patients (e.g., solid-organ transplant recipients, allogeneic hematopoietic stem cell transplant recipients). HEV: Hepatitis E virus; RNA: Ribonucleic acid; Ig: Immunoglobulin.