Description du projet
Mécanismes de la réponse de l’hôte à l’infection par l’hépatite D
L’hépatite D est le résultat de la co-infection de patients atteints d’hépatite B avec le virus de l’hépatite D (VHD). Il s’agit de la forme la plus grave de l’hépatite virale qui entraîne souvent une insuffisance hépatique ou un carcinome hépatocellulaire. Environ 20 millions de personnes sont infectées par le VHD dans le monde, mais les connaissances sur la physiopathologie de la maladie et l’interaction hôte-virus, qui expliquent la variabilité individuelle dans l’évolution de la maladie, sont limitées. Le projet D-SOLVE, financé par l’UE, vise à organiser un dépistage d’une grande cohorte de patients infectés par le VHD, suivi d’études visant à déterminer les mécanismes moléculaires et l’issue de l’infection afin d’identifier des approches personnalisées de surveillance et de traitement antiviral avec les traitements actuellement disponibles pour réduire la charge de la maladie et améliorer la qualité de vie des patients.
Objectif
Hepatitis D is by far the most severe form of chronic viral hepatitis frequently leading to liver failure, hepatocellular carcinoma and death. Hepatitis D is caused by coinfection of hepatitis B patients with the hepatitis D virus (HDV). Up to 20 Million individuals are infected with HDV worldwide including about 250.000 patients in the European Union. There is very limited knowledge on disease pathophysiology and host-virus interactions explaining the large interindividual variability in the course of hepatitis D. It is in particular unknown why 20-50% are spontaneously able to control HDV replication, why the majority but not all patients progress to advanced stages of liver disease and why only some patients show off-treatment responses to antiviral treatment with either pegylated interferon alpha or the novel HBV/HDV entry inhibitor bulevirtide. As HDV is an orphan disease, no multicenter cohorts of HDV infected patients are available with appropriate biobanking. There is also no reliable animal model available allowing to study host responses. Thus, there is an urgent clinical, social and economic need to better understand individual factors determining the outcome of infection and to identify subjects benefitting from currently available treatments. Hepatitis D is a protype infection which could hugely benefit from a novel individualized infectious medicine approach. We here aim to perform an unbiased screening of a large multicenter cohort of well-defined HDV-infected patients followed by mechanistic studies to determine the functional role of distinct molecules. Identified specific parameters could have an immediate impact on the personalized surveillance strategies and antiviral treatment approaches. D-SOLVE aims to reduce disease burden, improve patient?s quality of life and safe direct and indirect costs caused by HDV infection by combining exceptional clinical, immunological, bioinformatical and virological expertise from leading centers in Europe.
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HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinateur
30625 Hannover
Allemagne