Hepatitis E Virus (HEV) Infections

Dear Colleagues

Hepatitis E virus (HEV) is the predominant cause of an enterically acquired acute viral hepatitis with an estimated 20 million infections worldwide and 44,000 associated deaths each year. HEV is highly endemic in resource limited countries where the virus is spread through the fecal-oral route during large waterborne outbreaks. Current HEV outbreaks of 2018/2019 were reported to the World Health Organisation (WHO) from West-Africa. HEV is increasingly recognized as an emerging disease in industrialized nations since an increasing number of locally acquired (autochthone) human hepatitis E cases has been recognized raising considerable concern. In addition to the water-/food borne associated transmission pattern there is clear evidence indicating that HEV is a zoonotic pathogen, which can infect humans through consumption of undercooked meat of infected domestic pigs and wild animals. Therefore, it has become evident that the disease may represent a significant global health burden.

However, the understanding of the zoonotic potential and detailed epidemiological data of HEV infections is still improvable.

The course of HEV infection in immunocompetent individuals is most often asymptomatic. When presenting with symptoms, hepatitis E usually manifests as a mild and self-limiting disease; however, the overall mortality rate may be 1-3% in general populations. Certain risk populations such as persons with pre-existing liver diseases and pregnant women may develop severe complications including fulminant hepatic failure, pre-term labor and increased incidence of fetal and maternal death with a fatality rate of up to 30%.

The mechanisms leading to different clinical outcome of HEV infection especially in pregnant is not well understood and needs further input and investigation.

In immunocompromised persons, such as solid organ and hematopoietic stem cell transplant recipients, HEV infections can develop into a chronic progression and affected patients may have worse prognoses. Although the antiviral drug ribavirin (RBV) is used as an off-label treatment to a degree of success in treated patients, side effects often pose limitations. Prolonged treatment can select viral mutants that are less susceptible to RBV. Predicting chronicity of HEV infection, i.e., with characteristic biomarkers, and thus administering antiviral therapy as early as possible would pose a valuable opportunity for increased patient care and control of disease outcome.

Thus new insights into mechanisms leading to chronic hepatitis E and innovative antiviral treatment options are still needed.

Extrahepatic manifestation of HEV infection has been reported most commonly of the nervous system and the kidney while, e.g., Guillain-Barre syndrome, neuralgic amyotrophy, glomerulonephritis, meningitis, encephalitis, or myopathy could be associated with hepatitis E.

However, underlying mechanisms of the different manifestation and clinical outcome of extrahepatic HEV infection are still underreported but is of high interest.

Although HEV replication is thought to be controlled by the host immune system, viral factors (genotypes and mutants, virus diversity, virus evolution) can modulate HEV replication, infection and pathogenesis.

Limited knowledge exists on the contribution of virus-host interaction and HEV genome variants towards pathogenesis, immunological response, replication control and susceptibility to antiviral drugs; however, this limitation has to be reduced incrementally.  

In this Special Issue, we will summarize the current knowledge answering the many open questions albeit in part on HEV infection in terms of virological, immunological, one health (zoonosis) and global health level, in order to improve our knowledge on HEV pathogenesis, immunology, epidemiology and factors that influence HEV replication, chronification and risk assessment in humans and animals.

We thus invite submission of research and review manuscripts that cover any aspect of the pathogenesis, immunology, epidemiology, diagnosis, treatment and prevention of hepatitis E. I look very forward to your contributions which will give without any doubt a valuable and high ranking edition that will promote further developments in the exciting field of hepatitis E.

Thank you for your collaboration.

Prof. Dr. C. Thomas Bock
Guest Editor

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