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Serum Hepcidin in Inflammatory Bowel Diseases: Biological and Clinical Significance

Bergamaschi, Gaetano MD*; Di Sabatino, Antonio MD*; Albertini, Riccardo MD; Costanzo, Filippo MD*; Guerci, Marco MD*; Masotti, Michela MD*; Pasini, Alessandra PhD*; Massari, Alessandro MD*; Campostrini, Natascia MD; Corbella, Michela MD; Girelli, Domenico MD; Corazza, Gino Roberto MD*

doi: 10.1097/MIB.0b013e31829a6e43
Original Clinical Articles

Background: Hepcidin, a peptide produced by hepatocytes, regulates body iron homeostasis. Inflammation increases serum hepcidin, and its determination can be useful in the differential diagnosis of anemias during inflammatory diseases.

Methods: We measured serum hepcidin-25 and hepcidin-20 isoforms in 54 patients with inflammatory bowel diseases (IBD) and 54 reference subjects (36 healthy controls and 18 anemic patients without inflammation or renal failure). Disease activity, blood counts, iron status, and erythropoiesis-related parameters were obtained for all study subjects.

Results: In IBD hepcidin-25, the peptide bioactive isoform correlated positively with C-reactive protein and serum ferritin; an inverse correlation was observed with transferrin, the soluble transferrin receptor, and the soluble transferrin receptor to Log(ferritin) ratio. Similar correlations were found in reference subjects. Patients with anemia of inflammation had higher hepcidin-25 levels than those with iron deficiency anemia or a combination of iron deficiency anemia and inflammation (P = 0.0061). In patients with inflammation and serum ferritin concentration 100 to 200 ng/mL, hepcidin-25 was low, suggesting that these patients had iron deficiency. A serum hepcidin-25 concentration below 2.0 nM differentiated 85% of patients with iron deficiency anemia (with or without inflammation) from patients with anemia of inflammation. In IBD, hepcidin-20 correlated with both hepcidin-25 and C-reactive protein.

Conclusions: In IBD, iron stores, inflammation, and iron requirement for erythropoiesis influence serum hepcidin-25. Hepcidin-25 determination can be useful in the differential diagnosis of IBD-associated anemias. Serum hepcidin-20 is linked to hepcidin-25, but inflammation has an independent regulatory role on its concentration, indicating that hepcidin-20 may have a biological function.

Article first published online 17 July 2013

*Department of Internal Medicine, University of Pavia Medical School and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;

Clinical Chemistry Laboratory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; and

Section of Internal Medicine, Department of Medicine, University of Verona, Italy.

Reprints: Gaetano Bergamaschi, Clinica Medica I, Fondazione IRCCS Policlinico San Matteo, Piazzale Golgi, 27100 Pavia, Italy (e-mail:

Supported by a grant from Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

The authors have no conflicts of interest to disclose.

Received April 15, 2013

Accepted May 06, 2013

© Crohn's & Colitis Foundation of America, Inc.
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