Hepcidin as a Biomarker of Response to Antifibrotic Therapy in Idiopathic Pulmonary Fibrosis

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) may progress despite antifibrotic therapy, highlighting the need for biomarkers of early treatment-associated biological changes. This study aimed to assess the potential role of hepcidin in monitoring treatment response by evaluating pre- and post-treatment serum hepcidin levels in patients with IPF receiving antifibrotic therapy. Methods: This prospective observational cohort study included 38 clinically stable patients diagnosed with IPF according to the 2022 American Thoracic Society/European Respiratory Society (ATS/ERS)criteria between January and July 2025. Serum hepcidin was measured by ELISA at antifibrotic therapy initiation and month 3. Demographic data, pulmonary function tests, diffusing capacity for carbon monoxide (DLCO), and 6 min walk test results were recorded. Analyses were performed using SPSS 25.0. Results: Mean serum hepcidin decreased from 33.00 ± 16.74 to 24.41 ± 12.42 ng/mL (p < 0.001), with reductions observed in 30 of 38 patients (78.9%). Mean forced vital capacity (FVC) increased from 73.83 ± 18.10% predicted to 77.74 ± 15.70% predicted (p < 0.001). Median DLCO increased from 68.50 (51.00–80.50)% predicted to 72.50 (60.00–83.75)% predicted (p < 0.001). Six-minute walk distance did not change significantly (p = 0.078), nor did hemoglobin, C-reactive protein, or erythrocyte sedimentation rate. The change in hepcidin did not differ between the pirfenidone and nintedanib groups (p = 0.817). Although FVC and DLCO increased over three months, these short-term functional changes should be interpreted cautiously, as test familiarization, measurement variability, and regression to the mean cannot be excluded; therefore, they should not be considered evidence of fibrosis reversal or a direct treatment effect. Conclusions: Our study provides the first real-world data demonstrating a significant decrease in serum hepcidin following antifibrotic treatment in patients with IPF. These findings suggest that serum hepcidin may have potential clinical utility as a biomarker for assessing response to antifibrotic therapy in IPF.