Circulating lipocalin-2 as a potential biomarker for MASLD: a systematic review and meta-analysis

Lipocalin-2 (LCN2), an adipokine involved in inflammatory responses, lipid metabolism, and insulin resistance, has emerged as a potential biomarker for metabolic dysfunction-associated steatotic liver disease (MASLD). The present meta-analysis aimed to clarify the association between circulating LCN2 levels and MASLD and examine its association across different disease stages. A systematic search was performed in Scopus, Embase, PubMed, Web of Science, and Google Scholar through May 2026. Observational studies comparing circulating LCN2 concentrations between patients with MASLD and healthy controls or between simple steatosis and metabolic dysfunction-associated steatohepatitis (MASH) were eligible. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Thirteen studies comprising 18 datasets were included in the meta-analysis. The studies involved 2,716 participants, including 1,623 individuals with MASLD and 1,093 control subjects. The pooled analysis demonstrated significantly higher circulating LCN2 levels in patients with MASLD than in control subjects (SMD = 1.190, 95% CI: 0.358–2.023; p = 0.005). Furthermore, LCN2 concentrations were slightly but significantly higher in patients with MASH than in those with simple steatosis (SMD = 0.370, 95% CI: 0.049–0.690; p = 0.024). Subgroup analyses suggested that geographic region, study design, sample type, and assay technique may contribute to the observed variability in effect estimates. The findings suggest that LCN2 may represent a potential candidate biomarker for the noninvasive detection and characterization of MASLD. Further studies should determine its diagnostic and prognostic performance, establish clinically relevant cutoff values, and clarify its role in MASLD pathogenesis. PROSPERO registration number CRD420261438172.