Hepcidin and Iron Status in Patients With Inflammatory Bowel Disease Undergoing Induction Therapy With Vedolizumab or Infliximab

Abstract

Background Hepcidin, the systemic iron regulator, could be critical in differentiating iron deficiency (ID) from functional iron restriction in inflammatory bowel disease (IBD). We assessed hepcidin as a diagnostic ID marker and explored the relationship between hepcidin and its regulators in patients with IBD undergoing induction therapy with infliximab (IFX) or vedolizumab (VEDO). Methods Patients with active IBD receiving induction therapy with IFX or VEDO were included. Serum samples at baseline and after 6 weeks of induction therapy were analyzed for hepcidin, inflammation- and hypoxia-associated cytokines, and oxidative stress. Data were analyzed by stratifying based on the response at week 14. Results were compared with samples from age- and sex-matched healthy control subjects. Results Patients receiving induction therapy with IFX (n = 71) or VEDO (n = 51) and healthy control subjects (n = 50) were included. At baseline, hepcidin correlated positively with ferritin and negatively with soluble transferrin receptor/log ferritin index (P < .001). ID was prevalent in 96.7% of patients who had hepcidin levels below the median. Hepcidin accurately identified ID: the area under the curve (hepcidin) was 0.89 (95% confidence interval, 0.82-0.95; P < .001). In total, 75.4% of patients responded to induction therapy; inflammation, hepcidin, and ferritin decreased significantly, while transferrin increased during induction therapy. These changes were observed only in patients who responded to the therapy. Conclusions Hepcidin levels in IBD are primarily determined by ID, even in an inflammatory state. In addition, induction therapy can decrease hepcidin levels, which might lead to better bioavailability of iron supplements. Therefore, hepcidin is a potential diagnostic ID biomarker that could assist therapeutic decision making.

Potential Diagnostic Role of Hepcidin in Anemic Patients Affected by Inflammatory Bowel Disease: A Systematic Review

“…After the revision of these works based on the predetermined parameters described in the Material and Methods section (inclusion and exclusion criteria), 68 articles were evaluated as unsuitable for this systematic review, including 34 reviews, editorials and comments to articles or case reports; 16 were not in the area of interest, 12 did not provide a useful cohort of controls and 6 were pre-clinical studies. Only 12 were considered eligible for the systematic review at the conclusion of the revision process [18][19][20][21][22][23][24][25][26][27][28][29]. The analysis of the references of the selected articles did not add any additional suitable articles to the final selection.…”

“…The comprehensive analysis included 976 IBD patients and 402 Controls (the study by Stojkovic Lalosevic et al, 2020 [24] mentions the healthy controls but does not specify their number) The articles were published between 2009 and 2023 in Europe, the USA, China and Israel. A total of 10 studies were conducted with a prospective/monocentric design [18,[20][21][22][23][24][25][26]28,29], one study was cross-sectional and monocentric [19] and one study was observational and multicentric [27] (Table 1). The characteristics of the patients are described in Table 2.…”

“…Furthermore, almost all the studies classified the patients as anemic and non-anemic apart from Moran-Lev et al [20]. Hepcidin was quantified using different laboratory methods; ELISA marketed by different companies [18,20,21,23,24,29], Mass spectrometry [19,26] and RIA [22]. Three studies did not specify the analytical method used to evaluate hepcidin concentration [25,27,28] (Table 2).…”

“…Recently, different authors have studied hepcidin levels in the blood of IBD patients to verify its potential as a noninvasive biomarker able to connect inflammation and iron metabolism, especially in the presence of anemia [18][19][20][21][22][23][24][25][26][27][28][29].…”

Serum Ferritin Levels: A Clinical Guide in Patients With Hair Loss

“…49,50 Elevated Ferritin-Elevated ferritin may be difficult to interpret given the multitude of conditions that can cause it. 23,51,52 Elevated serum ferritin can be broadly characterized by increased synthesis due to iron overload, increased synthesis due to inflammation, or increased ferritin release from cellular damage. 34 Further complicating interpretation is the potential diurnal fluctuations in serum iron levels dependent on dietary intake and timing of laboratory evaluation, choice of assay, differences in reference standards, and variations in calibration procedures that can lead to analytic variability in the measurement of ferritin.…”