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.