Identification of novel biomarkers for the diagnosis of alcohol-associated liver diseases using metabolomics.

Alcohol abuse is a major cause of liver disease worldwide and is the most common cause of acute-on-chronic liver failure. Despite the high prevalence of alcohol-associated liver disease (AALD), there is currently a lack of sensitive and specific early biomarkers, resulting in diagnosis at late (irreversible) stages of disease progression. The objective of this research project is the identification of (a panel of) small-molecule biomarkers to diagnose early stages of AALD through an advanced metabolomics workflow. Identification of mechanistic biomarkers for AALD will be performed in an in vitro experimental setup, using HepaRG® liver cells exposed to ethanol. A unique and ultra-performant analytical system (two dimensional liquid chromatography-ion mobility spectrometry-quadrupole time-of-flight mass spectrometry) will be used to identify possible biomarkers. An in vivo proof-of-concept study will be performed to extrapolate the applicability of the in vitro identified biomarkers to an in vivo situation. For this purpose, plasma and liver tissue samples of patients suffering from alcoholic fatty liver disease and steatohepatitis, will be investigated. Obtained data will help to improve the current knowledge on the mechanisms of action of alcohol-induced hepatoxicity and to provide new input for adverse outcome pathways. The results of this research project can be used as a lead for a clinical cohort-study to diagnose different stages of AALD.

Keywords:METABOLOMICS, ETHANOL, BIOMARKERS

Disciplines:Medical metabolomics, Biomarker discovery, In vitro testing, Analytical toxicology, Clinical toxicology

Project type:Collaboration project