Soluble CD14 Levels Predict Liver Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Independently of Obesity and Type 2 Diabetes

Increased intestinal permeability has been implicated in metabolic dysfunction-associated steatotic liver disease (MASLD), but its relationship with liver fibrosis independent of metabolic risk factors remains unclear. The aim of this study was to investigate the relationship between markers of gut-derived immune activation and liver fibrosis in individuals with metabolic disease. We enrolled 139 adults (48.8 ± 11 years; BMI 33.7 ± 9.5 kg/m2; 50% type 2 diabetes); liver steatosis and fibrosis were estimated using the Hepatic Steatosis Index (HSI) and Fibrotic NASH Index (FNI); liver biopsies were available in a bariatric subgroup. Plasma soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP) levels were measured by ELISA kits, and the LBP/sCD14 ratio was calculated. MASLD was present in 78% of participants; in these individuals, sCD14 levels correlated with HSI and FNI (both p < 0.01). In multivariable analysis adjusting for age, sex, BMI, waist circumference, and type 2 diabetes, sCD14 was independently associated with advanced fibrosis (OR: 3.16, 95% CI 1.32–7.55; p = 0.010). This association was confirmed by histology (p = 0.02). Overall, these findings point to a link between gut-derived immune activation and fibrotic burden in MASLD and provide insight into the pathophysiological relevance of the gut–liver axis in metabolic disease.