Integrated Evaluation of Iron Metabolism, Hepcidin, and Red Cell Indices in Patients with Celiac Disease-associated Anemia

BACKGROUND: Anemia associated with celiac disease (CD) is a complex iron metabolism, inflammatory regulation, and erythropoiesis disorder. Measurement of hepcidin, iron markers, and red cell indices could enhance the diagnosis. AIMS OF THE STUDY: The aim of this study was to examine the levels of blood hepcidin, iron metabolism markers, and red cell indices in individuals with CD-related anemia and determine their significance for diagnosis and treatment. METHODOLOGY: This case–control study was performed at the Hematology Center in Nasiriyah, Iraq, from June 10, 2025, to March 1, 2026, in which a total of 90 patients with CD-associated anemia and 45 healthy matched controls were enrolled. Anemia was defined as associated with iron deficiency (CD-associated iron deficiency anemia [CD-IDA]) when the patient had both the anemia and a serum ferritin level of <15 ng/mL and with mixed or noniron deficiency (CD-associated mixed/noniron deficiency anemia (when the patient had anemia but did not meet the iron deficiency criteria. CD diagnosis was made on the basis of clinical presentation, anti-tissue transglutaminase serology, and consultation with a specialist. Standard biochemical assays, enzyme-linked immunosorbent assay, and automated hematology analyzers were used to evaluate serum iron biomarkers, hepcidin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), complet blood count (CBC), and red cell distribution width (RDW). RESULTS: Hematological indices, inflammatory markers, and iron metabolism were altered significantly in celiac patients with anemia when compared to controls. Hemoglobin, ferritin, transferrin saturation (TS), and hepcidin were significantly decreased, while transferrin, CRP, ESR, and RDW were significantly elevated in CD-IDA patients ( P < 0.001). Serum iron, ferritin, TS, and hepcidin levels were significantly decreased, whereas total iron binding capacity, transferrin, CRP, ESR, and RDW were significantly increased in CD-IDA patients ( P < 0.001). Hepcidin was significantly related to iron parameters and negatively to RDW. The diagnostic biomarker that was best identified by receiver operating characteristic analysis was ferritin (area under the curve = 0.921), followed by TS, hepcidin, and RDW. CONCLUSIONS: In CD-associated anemia, the iron metabolism is disturbed, the regulation of hepcidin is imbalanced, and the red cell indices are abnormal. Ferritin, hepcidin, TS, and hematological parameters could be combined to better evaluate and understand the anemia pathogenesis in CD.