Proteomic resolution of the MASLD cardiometabolic spectrum identifies sex-driven endotypes and predicts systemic mortality

The authors aimed to elucidate the molecular heterogeneity of metabolic dysfunction-associated steatotic liver disease (MASLD) and identify distinct sub-phenotypes that influence prognostic outcomes. Through latent class analysis and large-scale proteomic profiling, they discovered clinically relevant MASLD subtypes with significant sex differences and developed a four-protein score (PS4) that outperformed existing mortality prediction methods. This research highlights the biological pathways linking hepatic dysfunction to systemic mortality, offering a new framework for understanding MASLD's impact on long-term health.