Conicet researchers identify molecular markers to predict severe fatty liver disease

Argentine researchers at Conicet have achieved a significant scientific breakthrough by identifying key molecular markers that can predict severe forms of fatty liver disease. The condition, known as metabolic dysfunction-associated steatohepatitis (MASH), affects approximately 30% of the global adult population.

Published in the prestigious journal GUT, the findings enable the early identification of different disease subtypes. This advancement aims to optimize early diagnoses and facilitate the design of personalized therapies for individuals at higher risk of mortality. Traditionally, diagnoses focused on local liver damage, but this new approach reveals MASH as an active metabolic engine that influences systemic health, increasing risks for cardiovascular issues and cancer.

The research team utilized proteomics, a technique that measures thousands of blood proteins simultaneously, analyzing data from 500,000 individuals in the UK Biobank. This analysis led to the development of the PS4 Index, a diagnostic tool based on measuring four specific blood proteins: FTCD, ADGRG1, FABP1, and GAST. The PS4 Index dynamically assesses metabolic stress, immune cell traffic, and vascular integrity, offering superior predictive capabilities compared to conventional methods.

Furthermore, the study highlighted biological differences in disease progression based on sex. Advanced liver fibrosis was observed in 50% of women within high-risk subgroups, compared to only 20% of men. Carlos Pirola, a Conicet researcher, explained that aggressive clinical and molecular subtypes are associated with elevated mortality rates, primarily driven by tumors and heart conditions. This discovery paves the way for more targeted and effective treatments for MASH patients.

“

After a longitudinal follow-up of more than 15 years, we demonstrated that the most aggressive clinical and molecular subtypes show high mortality rates, driven predominantly by tumors and pathologies of the heart.