sTREM2 evaluation in women with metabolic dysfunction-associated steatotic liver disease: Advancing diagnostic approaches for early MASH.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease worldwide. Some patients progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by inflammation and fibrosis. MASH diagnosis still depends on invasive liver biopsy, as accurate and validated noninvasive biomarkers are lacking. We aim to investigate the potential of sTREM2 as a noninvasive diagnostic marker for detecting early MASH. This study involved 68 Caucasian women with severe-morbid obesity undergoing bariatric surgery, during which liver biopsies and fasting blood samples were collected. Soluble TREM2 levels in plasma were measured by ELISA, while hepatic TREM2 gene expression was analyzed via qPCR. Macrophage infiltration in liver tissue was assessed through CD68 immunohistochemistry. Serum sTREM2 levels were significantly higher in patients with MASH compared to those with NL (normal liver) and SS (simple steatosis), and ROC analysis demonstrated strong diagnostic performance for identifying early MASH (AUC=0.89). sTREM2 levels increased progressively with steatosis grade, lobular inflammation, and NAS score. Similarly, hepatic TREM2 mRNA expression was significantly elevated in MASH and correlated with histological severity, including steatosis, ballooning, and inflammation. CD68+ macrophage infiltration was significantly higher in MASH, and strong correlations were observed between sTREM2, TREM2 expression, CD68+ cells, and MASLD-related biochemical and histological features. Our findings show that sTREM2 is elevated in early MASH, correlates with hepatic TREM2 expression and macrophage infiltration, and reflects key histological and biochemical features of disease progression. These results support sTREM2 as a promising non-invasive serum biomarker for identifying reversible stages of MASH.