Pathogenesis and clinical features of severe hepatitis E virus infection

Abstract

The hepatitis E virus (HEV), a member of the Hepeviridae family, is a small, non-enveloped icosahedral virus divided into eight distinct genotypes (HEV-1 to HEV-8). Only genotypes 1 to 4 are known to cause diseases in humans. Genotypes 1 and 2 commonly spread via fecal-oral transmission, often through the consumption of contaminated water. Genotypes 3 and 4 are known to infect pigs, deer, and wild boars, often transferring to humans through inadequately cooked meat. Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms, such as jaundice. However, in immunosuppressed individuals, the disease can progress to chronic hepatitis and even escalate to cirrhosis. For pregnant women, an HEV infection can cause fulminant liver failure, with a potential mortality rate of 25%. Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection, which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease. As the prevalence of HEV infection continues to rise worldwide, highlighting the particular risks associated with severe HEV infection is of major medical interest. This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.

Keywords: Acute-on-chronic liver failure; Cirrhosis; Hepatitis E virus; Immune dysfunction; Open reading frames 1-4; Pregnancy.

Figure 1

Varying consequences of hepatitis E infection in individuals with healthy and distressed livers. HEV: Hepatitis E virus. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/Licenses/by/3.0/).

Figure 2

Overview of the impacts of acute-on-chronic liver failure resulting from hepatitis E virus infection in the context of pre-existing liver disease. HEV: Hepatitis E virus; ACLF: Acute-on-chronic liver failure. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/Licenses/by/3.0/).

Figure 3

Summary of the adverse effects of hepatitis E infection during pregnancy. HEV: Hepatitis E virus. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/Licenses/by/3.0/).

Figure 4

The effects of hepatitis E superinfection on liver health related to disease and therapeutic immunosuppression. HEV: Hepatitis E virus. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/Licenses/by/3.0/).

Figure 5

Several viral factors that increase hepatic injury induced by hepatitis E virus. The solid line with black arrows represents a direct influence, whereas the dashed line with arrows represents an indirect impact. Red lines show inhibitory processes. D29N, V27A, V239A mutations are associated with increased virulence. HEV: Hepatitis E virus; ISGs: Interferon-stimulated genes; IRF: Interferon regulatory factor; miRNA: MicroRNA; NF-κB: Nuclear factor-κB; ORF: Open reading frame; PTM: Post-translational modification; PTGS: Post-transcriptional gene silencing. Parts of the figure were drawn by using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/Licenses/by/3.0/).