SAN DIEGO—A handful of protein biomarkers accurately predicted the onset of metabolic dysfunction–associated steatotic liver disease years in advance of diagnosis, potentially opening the door to targeted early intervention, according to new research presented at DDW 2025.

“[MASLD] is the most common form of liver disease in the world, and it’s continuing to increase,” said investigator Shiyi Yu, MD, a resident in the Department of Gastroenterology at Guangdong Provincial People's Hospital, in China, during a media briefing before the conference. “Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms.” 

In their study, Dr. Yu and her co-investigators found that five protein biomarkers in the plasma proteomic blood profiles can predict MASLD up to 16 years ahead of diagnosis with 76% accuracy (abstract 323). 

The researchers collected 52,952 blood samples from participants in the UK Biobank and then assessed the participants’ health records over at least 16 years. They examined more than 2,700 different types of proteins for an eventual correlation with liver disease. 

Five plasma proteins—CDHR2 (AUC, 0.825), FUOM (AUC, 0.815), KRT18 (AUC, 0.810), ACY1 (AUC, 0.803), and GGT1 (AUC, 0.797)—were found to be associated with an increased risk for MASLD diagnosis. Participants with higher baseline levels of these proteins faced markedly increased risks of MASLD (hazard ratios, 7.05-9.81). 

These proteins indicated disease progression at an 84% accuracy rate five years before a diagnosis. The accuracy rate decreased to about 76% 16 years before onset. When using additional data points, such as body mass index and clinical biomarkers, accuracy increased to 90% five years before diagnosis and 82% at 16 years.

The researchers performed external validation using cohorts from different regions, which showed minimal AUC variation and further supported the strength of the model.

“These findings could be a game changer in how we screen and intervene for liver disease,” Dr. Yu said. “[This study shows] the power of proteomics to show biomarkers for liver disease.”

Based on these findings, Dr. Yu said, high-risk individuals with these proteins could receive preventive treatment or intervention well in advance of a diagnosis. Clinicians could draw a protein-based risk score from a patient’s blood and determine intervention strategies related to diet, physical activity and weight management.

“The field urgently needs effective biomarkers and predictive models,” Dr. Yu noted in a press release, “and our research shows that plasma proteins offer novel potential strategies for early prediction and intervention.”

—Karen Fischer