Background & Rationale
Non-Alcoholic Fatty Liver Disease has been redefined as Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), highlighting the central role of cardiometabolic risk factors (CMRFs) like obesity, dyslipidemia, hypertension, and insulin resistance. While individual CMRFs are linked to poorer outcomes in MASLD, their combined and interactive effects on disease progression, mortality, and liver-related events are not well quantified. Furthermore, clinically useful models integrating multiple CMRFs and genetic data to stratify patient prognosis are lacking.
Research Questions & Objectives
This project aims to leverage the rich phenotypic, genetic, and metabolic data in the UK Biobank to:
Systematically evaluate the joint effects of CMRFs on liver fibrosis and long-term clinical outcomes (all-cause mortality, cardiovascular events, chronic kidney disease, liver-related events) in individuals with MASLD.
Identify genetic and metabolic markers that modify the association between CMRFs and MASLD progression.
Develop and validate an integrated, clinically actionable risk-stratification model that combines clinical, metabolic, and genetic data to distinguish between low- and high-risk MASLD patients.
Scientific Rationale
By clarifying the synergistic impact of CMRFs, this research will identify high-risk subgroups and potential metabolic pathways for intervention. The expected outcome is a validated risk-stratification tool to guide monitoring and therapeutic strategies for MASLD patients in clinical care, with implications for public health policy and screening programs focused on multi-morbid metabolic dysfunction.