In 2023, an international consensus introduced the term steatotic liver disease (SLD) as an overarching category for liver fat accumulation of various etiologies, and replaced the term non-alcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD) for the metabolic subtype. The classification also defined metabolic dysfunction-associated and alcohol-related liver disease (MetALD) and alcohol-related liver disease (ALD) as distinct subcategories. While this new framework better reflects etiology and metabolic features, the epidemiology, metabolic comorbidities, genetic susceptibility, and natural history of these subtypes remain insufficiently characterized, especially regarding gene-phenotype associations and mechanistic evidence.
Objectives!1. To describe the prevalence, demographic distribution, and metabolic comorbidity patterns of MASLD, MetALD, and ALD in the UK general population, based on MRI and clinical data. 2. To identify metabolic, genetic, and lifestyle factors associated with the onset and progression of MASLD, MetALD, and ALD. 3. To utilize multi-omics and clinical variables to identify genetic markers linked to disease development, progression, and complications. 4. To develop and validate predictive models integrating imaging, genetic, biochemical, and clinical variables for identifying high-risk individuals and predicting adverse outcomes (including cirrhosis, major adverse cardiovascular events, and mortality). 5. To combine UKB population findings with laboratory-based experiments to functionally validate key candidate genes and pathways involved in disease pathogenesis.
