HOFER Benedikt

Characterisation of the Liquid Fingerprint of Distinct Clinical Stages of Advanced Chronic Liver Disease (ACLD)

The main aim of this project is to characterise the liquid fingerprint of pro- and anti-inflammatory signalling in advanced chronic liver disease (ACLD) via a combined experimental and translational approach. The experimental part will use established rodent models of ACLD to conduct a detailed assessment of inflammatory biomarkers, including TNF-alpha, IL-1b, IL-6, IL-10, MCP1(CCL2) and TLR4, as well as of hepatic haemodynamic parameters. Via a subsequent induction of acute-on-chronic liver failure (ACLF), a complication characterised by further deterioration of hepatic function and extrahepatic organ failure [1], the relative impact of pro-/anti-inflammatory cytokines as potential pathophysiological drivers of this process will be investigated. Histological stainings and molecular analyses of the liver tissues harvested from ACLF animal models will provide valuable insight into the molecular mechanisms. The experimental results obtained from the study of animal models will be validated in a prospective cohort of ACLD patients that is linked to a biobank containing blood, faecal matter and ascitic fluid samples, as well as liver tissue samples. Based on this biobank, our research project aims to characterise inflammatory processes in different stages of ACLD and distinct stages of portal hypertension. The prospective character of the human ACLD study will additionally enable us to monitor the dynamics of pro- and anti-inflammatory biomarkers over time and to evaluate the impact of aetiologic treatments on this liquid fingerprint in patients with ACLD.

Methods and Skills:

Animal studies; heamodynamic measurements in rats; immunohistochemistry; histological staining; translational research; polymerase chain reaction (PCR); enzyme-linked immunosorbent assay (ELISA)