Klinik für Innere Medizin IIGastroenterologie, Hepatologie, Endokrinologie und Infektiologie

Virus- and vaccine-induced adaptive immune responses in patients with chronic liver diseases

Chronic liver diseases, such as metabolic-associated steatohepatitis (MASH), autoimmune liver diseases or viral hepatitis are associated with immune dysfunction, which contributes to both disease progression and increased susceptibility to infections. This immune dysfunction is particularly relevant in patients with liver cirrhosis, where the immunological imbalance, termed cirrhosis-associated immune dysfunction (CAID), is characterized by a paradoxical state of systemic inflammation coexisting with immune suppression.

A main focus of the group is the characterization of this immune dysfunction in patients with viral hepatitis. T cells play an important role in the control of viral infections, as strong and multi-specific T cell responses are required to eliminate viral pathogens. However, viral escape mutations and T cell exhaustion are two mechanisms that can lead to impaired T cell responses and thus viral persistence. T cell impairment occurs frequently in individuals chronically infected with the Hepatitis B Virus (HBV), the Hepatitis C Virus (HCV), and in patients co-infected with both HBV and Hepatitis D Virus (HDV). Importantly, chronic viral hepatitis causes liver fibrosis and cirrhosis, which is associated with serious complications such as hepatocellular carcinoma. So far, the mechanisms underlying T cell failure are not yet fully understood, and therapeutic approaches for long-term restoration of impaired T cell functionality remain elusive. We are therefore interested in deciphering mechanisms of T cell failure in chronic HBV, HCV and HBV/HDV coinfection in order to develop novel strategies to achieve viral clearance.

Another focus of the group is the characterization of adaptive immune responses to viral infections and prophylactic vaccinations in patients with chronic liver disease as they are at higher risk of viral infection and a more severe course of infection, for example in pandemic viral infections such as SARS-CoV-2 or influenza infection. We therefore aim to decipher the adaptive immune response in these vulnerable patients following infection and vaccination, as this may have implications for future vaccine strategies.

We work in close collaboration with the TRANSLATIONAL EXPERIMENTAL IMMUNOLOGY LAB.