Distinct hepcidin patterns in Crohn’s disease and ulcerative colitis: links to iron homeostasis and inflammatory activity

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Abstract
Background and Aims: Hepcidin, the master regulator of systemic iron metabolism, is influenced by iron availability and inflammation. In inflammatory bowel disease (IBD), the interplay between iron deficiency and inflammatory activity remains incompletely understood. This study aimed to characterize hepcidin regulation in ulcerative colitis (UC) and Crohn’s disease (CD) in relation to iron status and inflammatory markers. Methods: In this cross-sectional multicenter study, 589 individuals were enrolled: 178 controls, and 130 UC and 281 CD patients. Patients were stratified by iron status and disease activity. Serum hepcidin, iron parameters, and inflammatory and clinical data were collected. Iron deficiency was defined using the ECCO criteria and a combined ferritin and transferrin saturation definition. Group comparisons, correlations, and multivariable linear regressions were performed. Results: Hepcidin correlated positively with C-reactive protein in CD (r = .125; P = .038) and negatively with fecal calprotectin in UC (r = −.311; P < .001). Using the ECCO definition, hepcidin levels in CD were higher than in controls within comparable iron-status categories (iron deficiency: 4.359 [IQR 2.094-8.906] ng/mL vs 2.300 [IQR 1.375-4.950] ng/mL, P = .019; normal iron stores: 10.402 [IQR 6.398-17.683] ng/mLvs 8.500 [IQR 5.300-12.150] ng/mL, P = .023). In UC, no significant differences from controls were observed, under the same criteria. In correlation analyses, ferritin showed the strongest association with hepcidin across groups (P < .001). Conclusions: Ferritin showed the strongest association with hepcidin across IBD, but regulation differed by disease. In UC, lower hepcidin levels were associated with intestinal inflammatory activity measured by fecal calprotectin, whereas in CD, higher hepcidin levels were associated with systemic inflammation despite iron deficiency. These findings highlight hepcidin’s potential as a biomarker linking iron status and inflammatory type in IBD.
Funding Information
  • Portuguese Inflammatory Bowel Disease Study Group (GEDII) and Vifor Pharma

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