Project Summary:
Metabolic dysfunction–associated steatotic liver disease (MASLD), previously called nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease affecting the U.S. population. The prevalence of the disease has gradually increased over the last few decades, and its estimated current prevalence is more than 50%. This disorder progresses in a significant proportion of affected patients to develop metabolic dysfunction–associated steatohepatitis (MASH). Metabolic risks, such as obesity, diabetes (DM), and hyperlipidemia, are associated with MASLD. The patients with MASH then develop cirrhosis and its complications. Most of these patients do not have any symptoms. Hence, the diagnosis occurs in a very small proportion of these patients before the onset of complications of cirrhosis. It is crucial to note that is no noninvasive, readily available diagnostic tool to diagnose this disorder or a pharmacological therapy to mitigate it. This lack of tools and therapies underscores the urgent need for research.
The prevalence of MASLD in Wisconsin population is higher than the national average. An interim analysis from the population screening of MASLD in Milwaukee suggests that more than 70% of the screened population have MASLD compared to the predicted 50% in the U.S. population, with a significant proportion appearing to have MASH (35%). The rates of obesity (38%) and DM (8%) in Wisconsin are also close to the national average (42% and 12%, respectively). Hence, with a high prevalence of MASLD locally—along with a relatively higher proportion of patients with MASH, the progressive form of MASLD—the development of a noninvasive biomarker to diagnose this disorder early before the onset of complications is essential. Understanding the disease process and considering an appropriate treatment will not only improve the quality of life of our community, but also significantly impact the health of the Wisconsin population, potentially saving lives and reducing healthcare costs.
This goal of this project is to develop an understanding of the relevant pathophysiological changes occurring in different metabolic processes, resulting in the pathological state we see in the histology. The project team aims to do this by evaluating the changes in different “omics” (proteomics, lipidomics, metabolomics, and their relevant RNA sequence variations) in different biological compartments of relevance to this disorder (blood, liver tissue, and urine).
Through this analysis, the researchers also aim to formulate a noninvasive plasma biomarker based on pathophysiological events in MASLD. The long-term goal is to characterize the biomarker by internal and external validation so that it can be used confidently and accurately in the general population.
Collaborators: University of Caliornia, Davis, Accura Science