New Research Identifies Key Biomarkers of Hepatic Steatosis and Liver Disease Progression
A team of researchers co-led by TGen, part of City of Hope, have uncovered important molecular signatures that could help predict the progression of hepatic steatosis, a liver condition linked to obesity and other metabolic disorders. The finding, published in Cell Reports Medicine, offer new insights into the biology of liver disease, providing a more detailed and dynamic understanding of how fatty liver disease develops and progresses.
Hepatic steatosis, commonly known as fatty liver, is a hallmark of metabolic-associated steatotic liver disease (MASLD). As obesity rates rise globally, the condition has become more prevalent, affecting over 30% of the population worldwide. It is a key contributor to serious liver diseases, including cirrhosis, liver cancer, and other systemic health issues such as cardiovascular disease and diabetes.
The study, which included data from nearly 5,000 individuals across several international cohorts, found that certain proteins are strongly associated with the early stages of hepatic steatosis. Importantly, these proteins were circulating biomarkers—proteins found in the blood. These biomarkers could serve as non-invasive indicators of liver health, potentially allowing for earlier detection and monitoring of disease progression in at-risk populations.
“By looking at blood-based markers, we can detect changes that reflect the liver’s condition, potentially reducing the need for biopsies,” said Ravi Shah, M.D., director of clinical and translational research in the Division of Cardiovascular Medicine at Vanderbilt University Medical Center and co-senior author on the study. “This approach may open up new possibilities for screening for and tracking metabolic liver disease, particularly in large populations where invasive biopsies are clinically risky.”
To gain deeper insights into the biology driving these blood-based markers, the research team turned to advanced genomics technologies.
“Our team used single cell and spatial transcriptomics approaches to localize the steatosis-associated genes within primary liver tissue and examine how they differ between healthy and steatotic livers,” said Nicholas Banovich, Ph.D., an associate professor at TGen and co-senior author on the study.
By mapping gene expression directly within liver tissue at a cellular and spatial level, the study revealed which liver cells—and where within the liver—these molecular changes were occurring.
“By contextualizing these changes, we are able to shift from predictors of disease to potential mechanisms,” said TGen’s Niran Hadad, Ph.D., a co-first author on the study.
The results are part of a growing body of research aimed at understanding how metabolic diseases like MASLD develop and how they can be managed more effectively. This study represents a significant step forward in identifying functional biomarkers that could inform both diagnostics and treatment strategies for liver diseases.
This research underscores the importance of combining clinical data with advanced molecular technologies to improve our understanding of complex diseases and develop more effective tools for prevention and treatment.
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