What Can Hepcidin Levels Reveal About Absolute Iron Deficiency in IBD?

Hepcidin levels can help distinguish between absolute iron deficiency and iron restriction in patients with inflammatory bowel disease (IBD) prior to initiating induction therapy. Therefore, hepcidin may be helpful in determining which induction therapy is optimal based on initial patient presentation, according to study findings published in Inflammatory Bowel Diseases.

Hepcidin systemically regulates iron. Elevated serum hepcidin levels are associated with iron malabsorption and iron restriction. Anti-inflammatory therapies used in the treatment of IBD may reduce hepcidin levels, increasing iron bioavailability.

Researchers conducted a retrospective study to determine the relationship between hepcidin, iron indices, biomarkers for inflammation and oxidative stress, and hypoxia during induction therapy in patients with IBD. They questioned whether hepcidin could be used as a diagnostic biomarker for iron deficiency in this patient population.

Researchers examined data on 130 adult patients with Crohn disease (CD), ulcerative colitis (UC), or unclassified IBD (IBD-U).

A total of 122 patients — 66 with CD, 48 with UC, and 8 with IBD-U — completed induction therapy with either vedolizumab (n=51) or infliximab (n=71) for 14 weeks. Results were compared with those obtained from 50 healthy control participants.

Researchers recorded serum levels of hepcidin, iron, ferritin, transferrin, total iron binding capacity, transferrin saturation, c-reactive protein (CRP), and fecal calprotectin as well as specific elements from a complete blood count (CBC) and comprehensive metabolic panel including estimated glomerular filtration rate at baseline and weeks 6 and 14 following induction therapy initiation. They also assessed baseline data determining disease activity levels according to the Montreal classification and endoscopic, radiologic, clinical, or biochemical findings.

Compared with the healthy control participants, patients with IBD demonstrated decreased hemoglobin (P <.01) and iron indices including ferritin and soluble transferrin receptors (P <.001 forboth).

In contrast, patients with IBD had higher CRP levels (P <.001), white blood cells (P <.01), and interleukins 1-beta (IL-1β) and 6 (IL-6;P <.001 for). Median hepcidin levels between the 2 groups did not differ significantly (21.19 ng/mL vs 13.52 ng/mL;P =.14).

Hepcidin levels correlated significantly with iron indices (positively with ferritin and negatively with soluble transferrin receptors; P <.001 for both). Weaker associations existed between hepcidin levels and hypoxia-related and inflammatory biomarkers, suggesting that hepcidin predominantly reflected systemic iron status over inflammation or hypoxia.

Researchers divided the patients into 4 quartiles based on baseline hepcidin levels. They observed that patients with hepcidin levels below the median were more likely to have iron deficiency (93.5% prevalence). Iron deficiency prevalence decreased to 33.3% in the fourth quartile among patients with highest hepcidin levels.

At baseline prior to induction therapy, hepcidin levels demonstrated the discriminative capacity to differentiate between patients with IBD who had and did not have absolute iron deficiency (area under the curve (AUC), 0.89; 95% CI, 0.82-0.95; P <.001). This differentiation was even more accurate for patients with CD (AUC =0.95) compared with patients with UC (AUC =0.87).

Researchers also noted that hepcidin levels and inflammatory and hypoxia-related biomarkers decreased more in patients receiving infliximab compared with vedolizumab. In general, patients who successfully responded to induction therapy exhibited significantly decreased hepcidin, potentially indicating increased iron bioavailability.

“Inflammation affects hepcidin levels,” the study authors wrote. “However, ID [iron deficiency] is the primary determinant of low hepcidin levels, even in an inflammatory

state. Hepcidin accurately differentiates between patients with and without absolute ID.”

Study limitations include the retrospective design, missing data on endoscopic disease activity for all patients, treatment with local or systemic steroids in a third of the cohort, lack of information on over-the-counter or prescription iron therapy supplementation, a relatively small sample size, potential lower accuracy on biomarker measurement testing, and lack of control over dietary iron intake (whether patients were vegan or vegetarian).

Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for full list of authors’ disclosures.