Understanding the individual host response against Hepatitis D Virus to develop a personalized approach for the management of hepatitis D

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.