Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, is now recognized as one of the most common chronic liver conditions worldwide. Recent research using data from the All of Us Research Program provides new insight into how metabolic risk factors and clinical outcomes vary across different populations in the United States.
This large-scale study, published in the Journal of Clinical and Translational Hepatology, analyzed more than 250,000 individuals and compared over 15,000 MASLD cases with a matched control group. The findings highlight how conditions such as obesity, diabetes, hypertension, and sleep apnea contribute to disease development and how these risks differ by age and ethnicity.
The research used electronic health record data from the NIH All of Us Research Program, one of the most diverse health databases in the United States. The study aimed to:
Participants included 15,060 MASLD cases and 75,300 matched controls.
The study confirmed that several metabolic conditions are strongly associated with MASLD. The most significant risk factors include:
Obesity emerged as the strongest risk factor overall. About 66 percent of MASLD patients had obesity compared with 41 percent of controls. This association was especially strong in younger individuals and Asian populations.
Type 2 diabetes was present in nearly 40 percent of MASLD patients, more than double the rate seen in controls. This reinforces the close relationship between insulin resistance and liver fat accumulation.
High blood pressure was also highly prevalent in MASLD patients, affecting over 64 percent of cases. Interestingly, hypertension was the strongest risk factor among Black participants.
Elevated cholesterol and triglycerides were common, affecting nearly 60 percent of MASLD patients.
Sleep apnea showed a significant association with MASLD, affecting about 29 percent of patients.
Thyroid dysfunction was less common but still independently associated with MASLD.
Type 1 diabetes was rare in both groups but still showed a statistically significant association.
One of the most important findings was that risk factors are not uniform across populations.
These differences suggest that MASLD is not a single-pathway disease but rather a condition influenced by genetics, lifestyle, and environmental factors.
The study also examined major health complications associated with MASLD.
Patients with MASLD had significantly higher rates of:
This supports the well-established link between fatty liver disease and cardiovascular risk.
MASLD was strongly associated with severe liver outcomes, including:
Although these outcomes were less common, they were significantly more frequent in MASLD patients compared with controls.
The study found higher levels of liver enzymes in MASLD patients, including:
Notably, a large portion of MASLD patients still had normal or only mildly elevated liver enzymes, suggesting that standard lab tests may miss early disease.
This research is important because it uses one of the largest and most diverse datasets available in the United States. It confirms that MASLD is closely linked to metabolic health and that risk profiles vary across different groups.
Key implications include:
The findings also highlight the need for personalized approaches to prevention and treatment.
The authors note several limitations:
Despite these limitations, the large sample size strengthens the reliability of the findings.
This large population-based study provides strong evidence that MASLD is closely linked with metabolic disorders such as obesity, type 2 diabetes, hypertension, and dyslipidemia. It also shows that these risk factors vary depending on age and ethnicity, which may help guide more personalized screening and prevention strategies.
MASLD is not only a liver disease but also a systemic metabolic condition associated with serious cardiovascular and hepatic complications. Early identification of metabolic risk factors remains essential for reducing long-term health consequences.
Hu KQ, Payrovnaziri SN, Ziogas A, et al. Metabolic Risk Factors and Clinical Presentations of Metabolic Dysfunction-associated Steatotic Liver Disease Using Data from the All of Us Research Program. Journal of Clinical and Translational Hepatology. 2026;14(2):137-145. doi:10.14218/JCTH.2025.00393
This article is for informational and educational purposes only. It is based on published research and is not intended to provide medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional for medical concerns or before making health-related decisions.
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