P0463Distinct Hepcidin Dynamics in Crohn’s Disease and Ulcerative Colitis: Links to Iron Homeostasis and Inflammatory Activity

Background Hepcidin, the master regulator of systemic iron metabolism, is influenced by iron availability and inflammation.1 In inflammatory bowel disease (IBD), iron deficiency and anaemia are common, yet how hepcidin is regulated in relation to disease phenotype, iron status and inflammatory burden remains incompletely understood.2 We aimed to characterise hepcidin regulation in ulcerative colitis (UC) and Crohn’s disease (CD) according to iron status and inflammatory markers. Methods In this cross-sectional multicentre study, 589 individuals were enrolled (178 healthy controls, 130 UC, 281 CD). Patients were stratified by iron status and activity. Serum hepcidin, iron parameters, and inflammatory and clinical data were collected. Iron deficiency was defined using the ECCO criteria2, which focuses on ferritin, 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 (CRP) in CD (r = 0.125; p = 0.038) and negatively with faecal calprotectin (FCAL) in UC (r=-0.311; p < 0.001) (Figure 1). Using the ECCO definition, median hepcidin levels in CD were higher than in controls within comparable iron-status categories (iron deficiency: 4.359 ng/mL [2.094-8.906] vs 2.300 [1.375-4.950], p = 0.019; normal iron stores: 10.402 [6.398-17.683] vs 8.500 [5.30012.150], p = 0.023). In UC, no significant differences from controls were observed, under the same criteria (Figure 2). In multivariable regression, ferritin was the strongest independent determinant of hepcidin in all groups (UC β = 0.569; CD β = 0.526; p < 0.001). Additional predictors included FCAL in UC (β=-0.153; p = 0.052), and in CD, CRP (β = 0.197; p < 0.001), age at diagnosis (β = 0.155; p = 0.002), and transferrin saturation (β = 0.140; p = 0.007). Conclusion Ferritin was the main driver of hepcidin in IBD, but regulation differed by phenotype. In UC, hepcidin suppression associated with active disease measured by FCAL, whereas in CD, systemic inflammation may have sustained hepcidin expression despite iron deficiency. These findings highlight hepcidin’s potential as a biomarker linking iron status and inflammatory phenotype in IBD. References: 1. Bergamaschi G, Di Sabatino A, Albertini R, et al. Serum hepcidin in inflammatory bowel diseases: biological and clinical significance. Inflamm Bowel Dis. Sep 2013;19(10):2166-72. doi:10.1097/MIB.0b013e31829a6e43 2. Dignass AU, Gasche C, Bettenworth D, et al. European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases. J Crohns Colitis. Mar 2015;9(3):211-22. doi:10.1093/ecco-jcc/jju009 Conflict of interest: Prof. Dr. Magro, Fernando: Fernando Magro served as speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor. Ministro dos Santos, Maria Paula: Received fees from AbbVie, Ferring, Janssen, Pfizer, Takeda, and Tillots. Tavares de Sousa, Helena: Personal Fees: Takeda, AbbVie, Janssen, Pfizer, Ferring, Biogen, Lilly - for presenting or advisory board Non-financial Support: Abbvie, Takeda, Janssen, Ferring, Faez Pharma, Tillots, Falk Pharma Roseira, Joana Selas: Received a speaking fee from AbbVie and Janssen Fernandes, Samuel Raimundo: None to declare Crespo, Ricardo: No conflict of interest Dias, Sandra: No conflict of interest Beatriz, Domingues: No conflict of interest Dias, Cláudia Camila: No conflict of interest Miranda, Rita: I declare that I have no conflicts of interest. Santiago, Mafalda: No conflicts of interest Portela, Francisco: consulting fees and support from the following companies: Abbvie, Falk, Ferring, Janssen, Lilly, Pfizer, Pharmakern, Takeda and Tillots.