Early Metabolic Injury – LiSym/EMI

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. In the coordinated submission from the VLN showcases, pillar I – “Early Metabolic Injury” looks into the transition from steatosis to non-alcoholic steatohepatitis (NASH) as the disease-defining moment in NAFLD: while simple steatosis has a good prognosis, patients with ensuing inflammation are at risk for liver cirrhosis and hepatocellular carcinoma. Building on the steatosis & LIAM showcases and the systems pharmacology clinical trial of VLN, a systems analysis of these early disease events will be performed to elucidate the molecular mechanisms that trigger disease progression: using the VLN biobank long-term followed patients and LiSyM animal models, we will profile the molecular pathways, including a systematic and quantitative analysis of lipids in relation to the structural alterations in liver tissue as determined by high-resolution quantitative imaging. The data will be used to generate models that integrate the molecular alterations with early morphological and pathogenetic changes, and can predict disease progression.