Category Research project
  • Mikrobiologie

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

Project status
Completed
Project start
Mar 2019
Project end
Feb 2023
Acronym
CHED
Department
Biologische Sicherheit
Website
https://www.bfr.bund.de/

Description and Objective

The aims of the project are investigations on the (molecular) epidemiology, clinical courses and molecular/immunological mechanisms of the chonic hepatitis E. 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. The main transmission pathway of HEV is in these countries through undercooked meat products. 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. 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. The BfRshort forGerman Federal Institute for Risk Assessment is involved in WP3 and WP4. In these work packages, the HEV genome diversity and the immune reaction against HEV will be investigated, with a special focus on the differences between acute and chronic infections.

Result

The BfRshort forGerman Federal Institute for Risk Assessment was involved in sub-projects, in which questions on the HEV genome diversity and the immune response were invetigated, mainly focusing on differences between acute and chronic infections. By this, several mutations could be identified in samples from chronically diseased patients, which were mainly localized in the polymerase region of the hepatitis E virus (HEV) genome. It was shown that HEV genomes from chronic, but not from acute cases, showed insertions and deletions in the hypervariable region of the HEV genome, which influenced the replication of HEV. It could be shown that some of the insertions did not induce resistence against antiviral therapy with ribavirin, but resulted in an increased replication of the virus. As these insertions were exclusively detected in chronic hepatitis E cases, they may explain - in part - the development of chronicity. In addition, a serum neutralization assays was developed for HEV. Using this assay it was shown that non-enveloped HEV was efficiently neutralized by specific antibodies; however, the quasi-enveloped HEV particle, which is also present in blood, was not neutralized. This finding can explain, why HEV can replicate during chronic infections for months without complete elimination by the immune system. The results of the project represent an important contribution for the management of the chronic hepatitis E in diagnostics and for development of possible therapeutic options.
Type of project

Third-party funded project

Research focus

Expositionsabschätzung und Bewertung biologischer Risiken

Organisational units and partners

Lead specialist group: Viren in Lebensmitteln (46)
Contact persons: Prof. Dr. Reimar Johne
External partner: Robert Koch-Institut, Charité - Universitätsmedizin Berlin, Ruhr-Universität Bochum, Friedrich-Loeffler-Institut, Bundesforschungsinstitut für Tiergesundheit

Funding body and grant number

Bundesministerium für Gesundheit
ZMVI1-2518FSB705

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