DIFFERENT LIPIDOMIC SIGNATURE IN EXTRACELLULAR VESICLES IN PATIENTS WITH MASLD- HCC: ANALYSIS OF DIFFERENT STAGES OF MASLD

Introduction and Objectives

MASLD ranges from isolated steatosis (STE) to steatohepatitis (MASH), cirrhosis (CIR) and hepatocellular carcinoma (HCC). Non-invasive markers have limited ability to identify different stages. Extracellular vesicles (EVs) could be a useful tool. This study aims to evaluate EVs lipid signature in disease progression.

Patients and Methods

EVs were isolated from patients with STE (n=25), MASH without fibrosis (MASH; n=25), CIR (n=25) and HCC (n=18), and compared to controls (CON; n=25). Lipidomics was performed by mass spectrometric analysis of sphingolipids, oxysterols and bile acids.

Results

Figure 1 shows a heatmap of lipid profiles. C24DHC was lower in MASLD vs CON, suggesting early alterations in membrane lipid homeostasis. C18-SM, C20-SM, C22-SM and Cer24-0 decreased in CIR and HCC vs others, indicating progressive disruption of sphingolipid metabolism with progression. C17-SM and C261-SM were significantly reduced in HCC vs CON, reflecting extensive lipid remodeling in late-stage. 7KC levels were significantly increased in HCC vs others, consistent with enhanced oxidative stress specifically associated with hepatocarcinogenesis. Bile acids TCA and CA were higher in HCC vs others, pointing to dysregulation of bile acid pathways in late-stage disease. All differences, p<0.05.

Conclusions

Lipid composition of EVs may reflect key molecular changes during MASLD progression. The reduction of sphingolipids and accumulation of oxysterols and bile acids in advanced stages suggest disrupted lipid metabolism, oxidative stress, and hepatocellular dysfunction. These findings support the potential of EV lipidomics as a non-invasive tool for disease staging and mechanistic insight.

Conflict of interest: None

Lipidomics heatmap