Diagnostic performance of serum hepcidin, soluble transferrin receptor, and heme oxygenase-1 in metabolic-dysfunction-associated steatotic liver disease and steatohepatitis

Objective: Iron dysregulation and oxidative stress are central to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to steatohepatitis (MASH). This study evaluated the diagnostic utility of serum hepcidin, soluble transferrin receptor (sTfR), and heme oxygenase-1 (HO-1) in patients with MASLD and MASH. Methods: A case–control study enrolled 120 adults aged 30–60 years, divided equally into simple steatosis (MASLD), MASH (assessed by FibroScan), and matched healthy controls. Serum hepcidin, sTfR, and HO-1 were quantified using sandwich ELISA. Diagnostic accuracy was assessed with receiver operating characteristic (ROC) curves, and independent associations were examined using Firth penalised logistic regression adjusted for age, body mass index (BMI), HbA1c, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Results: Hepcidin, sTfR, and HO-1 concentrations increased stepwise from controls to MASLD and MASH (all p < 0.001). For discriminating MASLD from controls, sTfR and HO-1 achieved areas under the curve (AUC) of 1.000 and 0.986, respectively. For differentiating MASH from controls, HO-1 (AUC = 1.000) and sTfR (AUC = 0.999) showed excellent performance. Multivariable analysis confirmed sTfR as an independent predictor of the MASLD spectrum after adjusting for metabolic risk factors. Conclusions: Hepcidin, sTfR, and HO-1 are promising non-invasive biomarkers for MASLD and MASH, reflecting underlying iron dysregulation. However, the near-perfect diagnostic accuracy observed in this single-centre discovery cohort requires external validation before clinical application.