D-SOLVE Cohorts (Cohort A and B)

Study Overview
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Brief Summary
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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 Hepatitis D is caused by co-infection with hepatitis B virus (HBV) and hepatitis D virus (HDV). This multicenter cohort should enable a comprehensive and unbiased biomarker screening of well-defined HDV-infected patients, followed by mechanistic studies to determine the functional role of distinct molecules. Patient surveillance strategies and antiviral treatment approaches could be personalized which should reduce clinical and social disease burden, improve quality of life and save direct and indirect costs caused by HDV infection.

Detailed Description
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The D-SOLVE consortium (Understanding the individual host response against Hepatitis D Virus to develop a personalized approach for the management of hepatitis D), aims for an unbiased screening of a large multicenter cohort of well-defined HDV-infected patients to better understand individual factors determining the outcome of infection and to identify subjects benefitting from currently available treatments. The D-SOLVE cohorts will be collected retrospectively as well as prospectively with clinical and virological data and biomaterial for the biomarker analysis. The aim of the cohorts is as following: Cohort A: To define the demographic, clinical, virological, and immunological features of a large cross-sectional cohort of 750 untreated and treated HDV patients at 4 EU centers. To compare these features among patients with different origin, gender, disease severity and treatment. To collect biological material to generate translational studies, aimed to better understand pathogenesis, natural history and treatment response. Cohort B: To identify histological and immunological features that are associated with fibrosis progression and clinical complications in patients with chronic HDV infection. The D-SOLVE consortium has received funding from the Horizon 2020 EU Horizon Call Personalised medicine and infectious diseases: understanding the individual host response to viruses (e.g. SARS-CoV-2) of the European Union (grant agreement No 101057917). The consortium is coordinated by Hannover Medical School (MHH) and the Centre for Individualised Infection Medicine (CiiM). Other partners are: Helmholtz-Zentrum für Infektionsforschung (HZI), Germany Institut national de la santé et de la recherche médicale (INSERM) Karolinska Institutet (KI), Sweden Karolinska University Hospital / Region Stockholm (KUH), Sweden Policlinico of Milan (PFM), Italy National Institute for Infectious Diseases Prof Dr Matei Balș (INBIMB), Romania Helmholtz-Zentrum für Informationssicherheit (CISPA), Germany The Cohorts and the biomarker screening are part of the EU-funded D-SOLVE Consortium.

Official Title
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D-SOLVE Cohorts (Cohort A and B)

Conditions
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HDV, HDV Infection, Chronic Liver Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Anti-HDV positive ≥18 years old Sex: m/f/d Informed consent for prospective procedures Exclusion Criteria: Anti-HDV negative

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort A<br>Cohort A: Patients chronically infected with HDV. Patients with and without cirrhosis and with and without viremia will be included. | |
| Cohort B<br>Cohort B: Patients chronically infected with HDV and with available historical liver biopsies (5-20 years old biopsies) and clinical follow-up data or current patients willing to receive a core biopsy or fine-needle liver-cell aspirate (FNA). Patients with and without cirrhosis and with and without viremia will be included. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biosample Screening | Identification of biomarkers that are associated with disease control, progression and treatment response by a multiomics approach that includes the investigation of: - the genome by the Illumina Infinium Global Screening array - the transcriptome by RNA-sequencing and single-cell RNA-sequencing (subset of samples) - the proteome by the Olink technology (high throughput proximity extension assay) - the metabolome by HPLC 1H-NMR ( 2k metabolite features) - the methylome (Illumina 850k array) - immune phenotypes by high dimensional spectral flow cytometry - Spatial transcriptomics and multiplex imaging of HDV-patient liver biopsies | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Definition of the demographic, clinical and virological features of the cohort. | Identification of immunological determinants of liver disease progression, viral control and treatment response by - scRNA/ATAC sequencing of Ag-specific T cells, NK cells and MAIT cells (PBMC) - spatial multiomics with feature barcoding technology of liver core biopsies - Validation of findings by 29-color flow cytometry, hepatoma HDV infection system and respective mouse models | 3 years | 
| Identification of virological and immunological features and characteristics that relate to disease severity and treatment response. | Establishment of a computational model to predict immune responses and disease phenotype | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HDV, Hepatitis Delta, chronic liver disease, patient cohort, biomarker