Single-cell landscape of peripheral immune cells in MASLD/MASH.

Area of Science:

• Immunology
• Hepatology
• Genomics

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) can progress to metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of liver cirrhosis.
• While liver inflammation is key in MASH, peripheral immune cell roles and single-cell profiles in MASLD/MASH are not well understood.

Purpose of the Study:

• To investigate the involvement of peripheral immune cell compartments in the progression of MASLD/MASH.
• To characterize single-cell profiles of peripheral immune cells in patients with MASLD/MASH.

Main Methods:

• Prospective cross-sectional study of patients with MASLD/MASH and healthy volunteers.
• Histological stratification and liver bulk RNA sequencing (RNA-Seq) of patient biopsies.
• Comprehensive bulk and single-cell RNA-Seq profiling of peripheral immune cells from blood samples.

Main Results:

• Disease activity scores (NAS) correlated with liver damage biomarkers and increased prevalence of diabetes and obesity.
• Liver bulk RNA-seq identified gene signatures associated with NAS, including upregulated fibrosis markers.
• Single-cell analysis revealed altered immune cell populations in MASH patients, notably increased immature B cells and myeloid suppressor cells compared to controls.

Conclusions:

• MASLD/MASH pathophysiology involves peripheral immune cell alterations early in the disease process.
• These findings suggest potential new avenues for developing diagnostic biomarkers and therapeutic strategies for MASH.