AIM: The aim of this study was to compare changes in serum hepcidin levels in paediatric patients with inflammatory bowel disease during therapy and correlate them with markers of iron metabolism, inflammation and type of treatment. METHODS: Children with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) were included in this longitudinal study. Blood and stool samples were collected to assess levels of serum hepcidin and markers of iron metabolism parameters and inflammation. The parameters were examined before treatment (baseline levels) and compared with levels in the follow-up period during maintenance therapy (mean follow-up of 39 months after diagnosis). RESULTS: Patients with CD (n = 30) had higher serum hepcidin levels (expressed as a median and interquartile range) at diagnosis than subjects with UC (n = 13). These levels significantly decreased during the follow-up (from 36.5 (11.5-79.6) to 2.1 (0.9-6.7) ng/mL). In contrast, no significant serum hepcidin level changes were observed in the UC patients (5.4 (3.4-16.6) vs. 4.8 (0.9-8.1) ng/mL). While hepcidin level changes correlated with disease activity and inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein), in CD patients, they correlated only with serum iron levels in patients with UC. Biological therapy was accompanied by a significant decrease in C-reactive protein and interleukin-6 compared to conventional anti-inflammatory therapy in CD patients. CONCLUSIONS: Children with CD had higher serum hepcidin levels on diagnosis compared to subjects with UC. During an anti-inflammatory therapy, serum hepcidin decreased in the CD group but remained consistently low in children with UC.

Department of Pediatrics Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc Olomouc Czech Republic

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry University Hospital Olomouc Palacky University Olomouc Olomouc Czech Republic

See more in PubMed

Sýkora J, Pomahačová R, Kreslová M, Cvalínová D, Štych P, Schwarz J. Current global trends in the incidence of pediatric-onset inflammatory bowel disease. World J. Gastroenterol. 2018; 24: 2741-63.

Wiskin AE, Fleming BJ, Wootton SA, Beattie RM. Anaemia and iron deficiency in children with inflammatory bowel disease. J. Crohns Colitis 2012; 6: 687-91.

Karaskova E, Volejnikova J, Holub D et al. Hepcidin in newly diagnosed inflammatory bowel disease in children. J. Paediatr. Child Health 2018; 54: 1362-7.

Levine A, Koletzko S, Turner D et al. ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J. Pediatr. Gastroenterol. Nutr. 2014; 58: 795-806.

Hyams JS, Ferry GD, Mandel FS et al. Development and validation of a pediatric Crohn's disease activity index. J. Pediatr. Gastroenterol. Nutr. 1991; 12: 439-47.

Turner D, Hyams J, Markowitz J et al. Appraisal of the pediatric ulcerative colitis activity index (PUCAI). Inflamm. Bowel Dis. 2009; 15: 1218-23.

Punnonen K, Irjala K, Rajamäki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 1997; 89: 1052-7.

Orkin SH, Nathan DG, Ginsburg D, Look AT, Fisher DE, Lux SE. Nathan and Oski's Hematology of Infancy and Childhood, 7th edn. Philadelphia, PA: Saunders Elsevier; 2009.

Levine A, Griffiths A, Markowitz J et al. Pediatric modification of the Montreal classification for inflammatory bowel disease: The Paris classification. Inflamm. Bowel Dis. 2011; 17: 1314-21.

Daher R, Manceau H, Karim Z. Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease. Presse Med. 2017; 46: e272-8.

Cavallaro F, Duca L, Pisani LF et al. Anti-TNF-mediated modulation of prohepcidin improves iron availability in inflammatory bowel disease, in an IL-6-mediated fashion. Can. J. Gastroenterol. Hepatol. 2017; 2017: 6843976.

Atkinson MA, Leonard MB, Herskovitz R, Baldassano RN, Denburg MR. Changes in hepcidin and hemoglobin after anti-TNF-alpha therapy in children and adolescents with Crohn disease. J. Pediatr. Gastroenterol. Nutr. 2018; 66: 90-4.

Suzuki S, Nakano S, Ando S et al. Hepcidin-25 gives an indication of the therapeutic effectiveness of tocilizumab in rheumatoid arthritis - Relationship between disease activity of rheumatoid arthritis and anemia. Rev. Bras. Reumatol. Engl. Ed. 2017; 57: 637-40.

Song SN, Iwahashi M, Tomosugi N et al. Comparative evaluation of the effects of treatment with tocilizumab and TNF-α inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients. Arthritis Res. Ther. 2013; 15: R141.

Isaacs JD, Harari O, Kobold U, Lee JS, Bernasconi C. Effect of tocilizumab on haematological markers implicates interleukin-6 signalling in the anaemia of rheumatoid arthritis. Arthritis Res. Ther. 2013; 15: R204.

Importance of Hepcidin in the Etiopathogenesis of Anemia in Inflammatory Bowel Disease