Selenoprotein P deficiency in MASLD: association with insulin resistance and liver fibrosis: a prospective case-control study

BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally escalating health concern. Selenoprotein P (SEPP1) is a hepatokine involved in selenium transport and antioxidant defense, with conflicting data on its role in MASLD. This study investigated serum SEPP1 as a potential non-invasive biomarker for disease severity and fibrosis staging. METHODS: This prospective case-control study enrolled 160 Egyptian participants (80 MASLD, 80 healthy controls). MASLD patients were stratified by fibrosis severity using vibration-controlled transient elastography (VCTE): non-significant fibrosis (< 8 kPa, n = 40) and significant fibrosis (≥ 8 kPa, n = 40). Anthropometric, biochemical (including HOMA-IR, lipid profile, liver enzymes), and SEPP1 (ELISA) measurements were compared. RESULTS: SEPP1 levels were significantly lower in MASLD patients versus controls (p < 0.001), with the lowest levels in the significant fibrosis subgroup (p = 0.025 vs. non-significant fibrosis). SEPP1 correlated inversely with BMI (r=-0.23, p = 0.004), HOMA-IR (r=-0.25, p = 0.001), and fasting insulin (r=-0.23, p = 0.004). MASLD patients exhibited higher insulin resistance, dyslipidemia, and liver enzymes (all p < 0.001). Logistic regression identified BMI (OR = 1.4, 95% CI:1.3-1.6) and HOMA-IR (OR = 1.4, 95% CI:1.1-2.0) as independent MASLD predictors. CONCLUSIONS: Reduced SEPP1 levels are strongly associated with MASLD severity and hepatic fibrosis. Its inverse correlation with insulin resistance and stepwise decrease with advancing fibrosis position SEPP1 as a promising simple biomarker for metabolic dysfunction and non-invasive fibrosis risk stratification. This is particularly relevant in high-burden populations like Egypt, where accessible tools are urgently needed to guide early intervention, and further studies should explore whether SEPP1 modulation or selenium supplementation could mitigate liver fibrosis progression.