Neumann-Haefelin, Christoph | Meli-Lang, Julia - B 06

Background: Chronic Hepatitis B virus (HBV) infection is a major global health issue with severe complications such as cirrhosis and hepatocellular carcinoma (HCC). During the last decades, the incidence of the metabolic syndrome has rapidly increased, making metabolic dysfunction-associated steatotic liver disease (MASLD) the second-leading cause of liver disease. Comorbidity of chronic HBV and MASLD is thus frequent and affects the clinical course and outcome of chronic HBV infection. However, little is known on the underlying immunological mechanisms. We aim to address this knowledge gap.

Rates of MASLD are rising, reaching 30% in Europe. Thus, a growing number of individuals with chronic HBV infection have comorbidity, increasing the risk for severe complications (e.g. cirrhosis, HCC). Superior viral control of HBV in patients with concurrent MASLD suggests a differential regulation of HBV-specific CD8+ T cells in this condition, at the same time contributing to immunopathology. Uncovering the underlying mechanisms will foster development of urgently needed immunotherapeutics.

1. Analyse repertoire, phenotype and function of HBV-specific CD8+ T cells in overall 50 matched patients with or without concurrent MASLD
2. Rare populations of HBV-specific CD8+ T cells will be identified ex vivo by peptide/MHC-I tetramer enrichment and analysed with multi-parametric flow cytometry
3. Repertoire and function will be determined by multi-parametric flow cytometry after peptide-specific expansion of HBV-specific CD8+ T cells in vitro
4. The overall immune landscape will be analysed in serum and liver biopsy samples

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