LOS ANGELES — More than a third of the world’s population is affected by metabolic dysfunction-associated steatotic liver disease (MASLD), the most common chronic liver disease globally. This condition, characterized by fat accumulation in the liver, is linked to five key conditions: obesity, Type 2 diabetes, high blood pressure, high blood sugar, and low HDL cholesterol, often referred to as “good” cholesterol. These conditions are known as cardiometabolic risk factors due to their impact on heart health and metabolism.
MASLD can progress to severe illnesses, including advanced liver, heart, and kidney disease. However, there has been limited research on whether specific cardiometabolic risk factors are more strongly associated with mortality in MASLD patients than others.
The Deadliest Cardiometabolic Risk Factors
In a groundbreaking study published in Clinical Gastroenterology and Hepatology, researchers from Keck Medicine of USC have identified three cardiometabolic risk factors that significantly increase mortality risk for MASLD patients: high blood pressure, pre-diabetes or Type 2 diabetes, and low HDL cholesterol. According to the study, these factors raise the risk of death by 40%, 25%, and 15%, respectively.
“MASLD is a complicated disease, and this study sheds new light on where doctors may want to focus their efforts when treating patients,” said Norah A. Terrault, MD, a hepatologist with Keck Medicine and a senior author of the study. “Knowing which aspects of MASLD might lead to poorer outcomes can help us offer patients the best possible care.”
The study’s findings were consistent regardless of the number or combination of cardiometabolic risk factors present, and they held true across different genders, sexes, races, and ethnicities. Researchers were particularly surprised to find that high blood pressure posed a greater mortality risk than diabetes, challenging previous assumptions about the disease.
“Until now, it was commonly thought that diabetes was the most pressing health problem for MASLD patients, which is a key insight,” noted Matthew Dukewich, MD, PharmD, MS, a USC transplant hepatology fellow and lead author of the study.
Impact of Obesity and Additional Risk Factors
The study also highlighted the role of obesity, the most prevalent cardiometabolic risk factor for MASLD. The research indicated that mortality risk increases with a patient’s body mass index (BMI), a measure of body fat based on height and weight. The higher the BMI, the greater the association with death.
Furthermore, the study contributes to a growing body of evidence suggesting that patients with more cardiometabolic risk factors experience worse outcomes. Specifically, the research found that the risk of death in MASLD patients increased by 15% for each additional cardiometabolic risk factor.
Research Methodology and Future Directions
To conduct the study, researchers utilized data from the National Health and Nutrition Examination Survey (NHANES), which collected health information from U.S. children and adults between 1988 and 2018. Out of 134,515 participants aged 20 years or older, approximately 21,000 were identified as having MASLD. The study authors analyzed all-cause mortality rates by individual cardiometabolic risk factors to draw their conclusions.
Looking ahead, the researchers aim to explore further studies examining the genetic background, dietary habits, and alcohol use of patients in relation to MASLD outcomes. This approach seeks to provide more comprehensive risk profiles and identify those most in need of interventions.
“The more we can understand about the drivers of the disease, the more we can identify those most in need of interventions and prioritize our resources for enhanced outcomes,” said Terrault.
Liyun Yuan, MD, a transplant hepatologist with Keck Medicine, also contributed to the study. The findings underscore the importance of targeted healthcare strategies to improve the prognosis for MASLD patients worldwide.
