A team of researchers identified a panel of five plasma proteins that can predict the development of metabolic dysfunction-associated steatotic liver disease up to 16 years before symptom onset. This discovery could enable early intervention strategies.
The proteomic signature—which consists of CDHR2, FUOM, KRT18, ACY1, and GGT1—demonstrated 83.8% predictive accuracy 5 years prior to disease manifestation and 75.6% accuracy at 16 years prediagnosis. When combined with clinical parameters including BMI and exercise metrics, the predictive model showed improved accuracy rates of 90.4% and 82.2% at 5 and 16 years, respectively.
"Imagine if we could predict risk of metabolic dysfunction-associated steatotic liver disease (MASLD) years before it starts," said Shiyi Yu, MD, resident physician in the department of gastroenterology at Guangdong Provincial People's Hospital in China. "Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms. The field urgently needs effective biomarkers and predictive models, and our research shows that plasma proteins offer novel potential strategies for early prediction and intervention."
In their observational study, the researchers analyzed blood samples from more than 50,000 participants in the UK Biobank and tracked their health records for over 16 years. They screened more than 2,700 proteins to identify the five biomarkers associated with subsequent MASLD development.
MASLD, which has supplanted the previously used term NAFLD (nonalcoholic fatty liver disease), is associated with up to twice the mortality rate compared with the general population. The disease's prevalence continues to increase globally.
The proteomic signature's predictive capability was subsequently validated in a separate Chinese cohort, which demonstrated cross-population applicability. "We achieved similar results when we tested this predictive model in a separate cohort of people in China, further supporting the robustness of the model and showing it can be effective across diverse populations," Dr. Yu noted.
The research team acknowledged that the study design did not establish causality between the identified plasma proteins and MASLD pathogenesis. Further investigations are currently underway to explore potential mechanistic pathways.
Dr. Yu will present the complete findings in the abstract session "Plasma proteomic profiles predict metabolic dysfunction-associated steatotic liver disease up to 16 years before onset" (abstract 323) at 8 a.m. PDT on Sunday, May 4, during Digestive Disease Week 2025.
Source: DDW