The new TRR 412 Metabolic Dysfunction-Associated Steatotic Liver Disease: From Pathophysiological Mechanisms to Translation into Tailored Therapeutic Concepts (Berlin / Dresden).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting around 30% of the population. It represents the hepatic manifestation of the metabolic syndrome and can progress to severe complications such as cirrhosis and hepatocellular carcinoma, with fibrosis as the key determinant of outcome. Current treatments, including the first liver-targeted pharmacotherapies, show limited efficacy in reversing fibrosis. The multidisciplinary consortium of the newly established transregional collaborative research center TRR 412 at the Charité Berlin and Dresden University of Technology aims to achieve a deeper mechanistic understanding of MASLD, promoting a holistic view that integrates pathogenic pathways of metabolic injury, inflammation, and fibrosis. MASLD is a complex and heterogeneous disease involving multiple liver cell types, and pathomechanisms are not (always) hierarchical, but intertwined across disease stages. In depth definition of the liver-specific molecular and cellular mechanisms driving MASLD progression will enable the development of innovative, mechanism-based therapies as well as improved patient stratification and personalized treatment approaches.