A large-scale study published in the Journal of Clinical and Translational Hepatology has identified several common health conditions—including obesity, hypertension, hyperlipidemia, obstructive sleep apnea, and hypothyroidism—as independent metabolic risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD), a condition increasingly recognised as one of the most prevalent chronic liver disorders globally.
The research team, led by Ke-Qin Hu of the University of California, Irvine, analysed electronic health record data from the “All of Us” cohort, one of the largest and most diverse health databases in the United States. The study evaluated 15,060 individuals diagnosed with MASLD and compared them with 75,300 frequency-matched controls to assess the relationship between metabolic risk factors and disease development.
Findings showed that MASLD affected about 6.0% of the study population. Individuals with the condition displayed markedly higher rates of multiple metabolic disorders compared with the control group. Obesity was present in 66.1% of MASLD patients versus 41.3% of controls. Similarly elevated differences were observed for type 2 diabetes (39.5% vs 16.9%), hypertension (64.3% vs 38.6%), hyperlipidemia (59.8% vs 37.3%), obstructive sleep apnea (28.9% vs 13.4%), and hypothyroidism (21.2% vs 13.4%).
The study also found that the influence of these risk factors varied across demographic groups. Obesity emerged as the strongest independent risk factor among Asian, White, and Hispanic populations, particularly in individuals under 50 years of age. In contrast, hypertension was identified as the most significant risk factor among Black participants.
Beyond metabolic associations, MASLD was also linked to a higher likelihood of serious clinical complications. Patients with the condition showed increased rates of cardiovascular events such as coronary artery disease and myocardial infarction, as well as severe liver outcomes including cirrhosis and hepatocellular carcinoma. Elevated liver enzymes—markers of liver injury such as alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase—were also more common among affected individuals.
According to the authors, the variation in risk profiles across race, ethnicity, and age groups may reflect a combination of genetic susceptibility and environmental influences. They suggested that these differences could help shape more targeted prevention and treatment strategies for MASLD in the future.
One of the study authors disclosed a financial relationship with Madrigal Pharmaceuticals, though the research itself was based on population-level data analysis.
As MASLD continues to gain recognition as a major global health concern, the findings underscore the importance of early identification and management of metabolic conditions, particularly in high-risk populations where multiple risk factors often overlap.