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Characterization of chronic hepatitis E in Germany: molecular epidemiology, pathophysiology and clinical aspects (CHED)

03/2019-02/2022

This third-party funded project is conducted in the framework of the BfR research programme on human, animal and environmental health (One Health)

Support programme of the Federal Ministry of Health (BMG): Zoonotic infectious diseases and pathogens with specific resistances

BMG grant number: ZMVI1-2518FSB705

Project homepage: -

Project description:

Hepatitis E virus (HEV) infection is the leading cause of acute viral hepatitis worldwide. In industrialized countries, HEV infection is endemic, largely underdiagnosed and underestimated public health problem. Newer data for Germany assume > 400,000 new infections/ year. Although the HEV infection is usually acute and self-limiting or clinically asymptomatic, it has been observed that the infection may persist in specific patient populations. Chronification of HEV is often life threatening. The mechanisms leading to chronic hepatitis E infection (CHE) are poorly understood. Accordingly, interdisciplinary studies are needed to better understand this zoonotic infectious disease with a chronic course. The aim of the project is to investigate the (molecular) epidemiology, clinical progression and molecular and immunological mechanisms of CHE. Specific questions to be answered within the project are:

(1) What is the epidemiology, incidence and frequency as well as demography of CHE?

(2) What are the clinical histories of CHE? Are there any risk factors / risk groups?

(3) What is the genetic diversity of HEV in CHE. Do HEV variants of CHE show a replication advantage and an altered pathogenicity through adaptation, immunodeficiency or drug treatment?

(4) What is the immune response in CHE patients and how does it contribute to the prognosis?

The translation of the newly gained insights will feed into diagnostics, patient management and the evaluation of CHE in the healthcare system.

BfR part of the project:

The BfR is involved in WP4 (Immune Reaction). In this work package, the immune reaction against HEV will be investigated, with a special focus on the differences between acute and chronic infections. In this context the question should be answered if differences in the immune reaction against HEV can explain the differences in severity of disease courses. To this end, assays will be developed, which can investigate the neutralizing (protecting) activity of antibodies against HEV. A cell culture system, which has been established at the BfR, will further be optimized and used for the measurement of the neutralizing activity of patient sera. The results should help tu explain the reasons for the different clinical outcomes of HEV infections in humans and also to identify immunological parameters, which can be used to estimate the prognosis of the disease.  

Project partners:

• Robert Koch-Institut
• Charité Universitätsmedizin Berlin
• Ruhr Universität Bochum
• Friedrich Löffler-Institut

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