Case example: Principles of Hepatitis E virus replication, resistance, and chronic persistence
Hepatitis E virus is one of the most common causes of acute viral hepatitis worldwide with an estimated 20 million infections per year. Although the mortality rate is under one per cent among the general population, pregnant woman can have a fatality rate of up to 30 %. Additionally, chronic hepatitis E has increasingly become a significant clinical problem in immunocompromised patients potentially leading to liver cirrhosis and liver failure.
Treatment options of fulminant infections are limited. Ribavirin remains the treatment of choice in non-self-limiting infections, however, should be carefully considered due to possible side effects and resistance development. Therefore, progress in the understanding of principles in HEV replication, resistance and persistence should contribute to improved control and treatment of HEV infections.
In the last years, we have established HEV cell culture systems and recently used these cell culture models to assess the effect of different interferons against HEV (Todt et al. Antimicrobial Agents and Chemotherapy 2016). Furthermore, we could demonstrate for the first time in tissue culture that HEV replication is not restricted to the liver and can potentially complete the full viral life cycle in neuronal-derived tissues explaining neurological disorders during HEV infection (Drave et al. Journal of Viral Hepatitis 2016) as well as human placenta-derived cells (Knegendorf et al. Hepatology communication 2018).
In case of ribavirin treatment, we could show that the drug applies mutagenic pressure on the viral genome, which may result in viral elimination and may also lead to the selection of resistant variants in patients who do not respond.
Finally, we could demonstrate that deep sequencing technology may in the future serve as a valuable tool to identify patients at risk of treatment failure (Todt et al. Gut 2016). Therefore, it may become an important component in the clinical management of patients with chronic hepatitis E and for personalized antiviral strategies in general.
In the future, we aim to identify novel antiviral against HEV and to uncover host factors required for HEV replication that could be new potential drug targets. In addition, mechanisms of drug resistance and viral persistence will be elucidated.
Hepatitis E virus infections are usually subclinical and are considered as an underrated disease by physicians. The number of infections worldwide is estimated at 20 million infected people per year. In our latitudes, primarily...
Hepatitis E virus infections seem to be an underrated risk - probably because the course of desease is characterised by a mild progression. The Robert-Koch-Institute estimates, that there are 300.000 people infected with that...