Surprising study reveals what really kills fatty liver disease patients
University of Southern California - Health Sciences
More than a third of the world's population is affected by
metabolic dysfunction-associated steatotic liver disease, or MASLD, the most
common chronic liver disease in the world.
MASLD occurs when fat builds up in the liver and is
associated with one or more of five conditions: obesity, Type 2 diabetes, high
blood pressure, high blood sugar and low HDL cholesterol, known as
"good" cholesterol. These conditions are characterized as
cardiometabolic risk factors because they affect the heart or metabolism.
MASLD can lead to serious illness, such as advanced liver,
heart and kidney disease, but little research has been done to examine if
certain cardiometabolic risk factors for those with MASLD are more associated
with death than others.
The deadliest cardiometabolic risk factors
Now, a new study from Keck Medicine of USC published
in Clinical Gastroenterology and Hepatology reveals that three
of the cardiometabolic risk factors carry the greatest risk of death for those
with MASLD: high blood pressure, pre-diabetes or Type 2 diabetes, and low HDL,
which raise the risk of death by 40%, 25% and 15%, respectively.
These results were independent of how many or which
combination of cardiometabolic risk factors patients had, and held steady
despite individuals' gender, sex, race or ethnicity.
"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."
Researchers were especially surprised to discover that high
blood pressure was associated with a higher chance of death than diabetes, said
Matthew Dukewich, MD, PharmD, MS, a USC transplant hepatology fellow and lead
author of the study. "Until now, it was commonly thought that diabetes was
the most pressing health problem for MASLD patients, which is a key
insight."
The study also found that obesity, the most common
cardiometabolic risk factor of MASLD, can substantially raise the risk of
mortality depending on a patient's body mass index (BMI), which is a formula
used to estimate body fat percentage based on an individual's height and
weight. The higher a patient's BMI, the higher the association with death.
Additionally, the research adds to the growing body of
research that patients with more cardiometabolic risk factors have poorer
outcomes. The study found that the risk of death in MASLD patients increased by
15% for each additional cardiometabolic risk factor present.
How the study was conducted
Researchers used data from the National Health and Nutrition
Examination Survey (NHANES), which collected health information about children
and adults in the United States from 1988-2018, the most current year for which
data was available for their study. Out of 134,515 participants 20 years or
older, some 21,000 patients qualified as having MASLD.
The study authors tracked all-cause mortality rates by
individual cardiometabolic risk factors to reach their conclusions.
Looking ahead, the study authors hope to conduct further
studies examining patients' genetic background, dietary habits and alcohol use
in relation to MASLD outcomes to provide more comprehensive risk profiles.
"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, is also a study author.
Journal Reference:
- Matthew
Dukewich, Jennifer L. Dodge, Liyun Yuan, Norah A. Terrault. Differential
Effects of Cardiometabolic Risk Factors on All-Cause Mortality in US
Adults with Metabolic Dysfunction-Associated Steatotic Liver Disease
(MASLD). Clinical Gastroenterology and Hepatology, 2025;
DOI: 10.1016/j.cgh.2025.09.003
