Genetic Study of Advanced Metabolic Dysfunction-Associated Steatotic Liver Disease MASLD Using Whole-Genome Sequencing to Understand Disease Progression and Risk

What this Trial Is About

Metabolic Dysfunction-Associated Steatotic Liver Disease MASLD is a common cause of chronic liver disease affecting over 30% of people globally. It is linked to insulin resistance and cardiometabolic issues, and in some cases, it can progress to steatohepatitis MASH, leading to serious liver damage, fibrosis, cirrhosis, or liver cancer. The condition has a strong genetic component, but many genetic factors remain unknown, especially rare variants and somatic mutations that may influence disease progression. This study focuses on understanding these genetic aspects to improve disease management. The research involves analyzing genetic profiles through Whole-Genome Sequencing WGS of blood samples from 800 patients with advanced MASLD and 2000 control individuals with metabolic risk factors but no MASLD. Additionally, 80 liver tissue samples from MASLD patients will be sequenced to identify somatic mutations. The study aims to discover new genetic variants, develop polygenic risk scores for better risk prediction, and find potential targets for treatment. Participants will provide blood samples for DNA sequencing, and patients with advanced MASLD may also provide liver tissue samples. Researchers will assess genetic information to identify risk factors and mechanisms behind disease progression. The primary outcome is identifying genetic risk for advanced MASLD within 11 months. The study will enhance understanding of MASLD biology and may lead to improved risk stratification and therapeutic options. The study runs from September 2025 to August 2026.

DEFINITION OF THE GENOMIC LANDSCAPE OF MASLD