Proteomic profiling of circulating EVs revealed key proteins associated with disease progression, including cathepsin B (Ctsb) and prosaposin (Psap) in early MASLD, and coagulation factor XIII A chain (F13a1) and polymeric immunoglobulin receptor (Pigr) in early MASH. Here, PIGR is linked to metabolic dysfunction-associated steatohepatitis.