Despite the high
prevalence and serious clinical implications of metabolic associated
steatohepatitis (MASH) in patients with type 2 diabetes (T2D), MASH is usually overlooked in clinical practice, due to the lack of accurate biomarkers. The inventors evaluated the ability of
plasma large
extracellular vesicles (lEVs) to serve as noninvasive biomarkers for the diagnosis of MASH, in particular in T2D patients. Proteomic analysis identified Transferrinreceptor on lEVs (TFRC-lEVs) as associated with MASH. The inventors thus measured TFRC- lEVs on
plasma samples from patients included in the derivation cohort. The proportion of patients with TFRC-lEVs concentration > 61 ng / mL was significantly higher in patients with MASH than in those with
steatosis. TFRC-lEVs > 61 ng / mL remained associated with MASH after adjustment on either usual laboratory variables, or on the NASH-Test or on the Fibroscan FAST-
score. When combining TFRC-lEVs with available methods the
population suspected of having MASH was 32% and 29%, versus 22% and 16% for NASH-test or FAST
score alone, without decreasing specificity. In conclusion, TFRC-lEVs, a marker of
hepatocyte ballooning, is a promising biomarker for MASH. It could be used for patients' screening to enlarge recruitment of patients with MASH in clinical trials.