Hepcidin In Children Research Articles

Hepcidin in Children and Adults with Acute Leukemia or Undergoing Hematopoietic Cell Transplantation: A Systematic Review.

Simple SummaryIn this systematic review, we summarized the observational studies on hepcidin in patients treated for acute leukemia or undergoing hematopoietic cell transplantation (AL/HCT). Thanks to the rigorous methodology used, we were able to trace the available literature conscientiously and draw the following conclusions: (1) in both children and adults with AL and qualified for HCT, hepcidin levels are high regardless of the phase of the disease or iron resources;, (2) AL therapy, and HCT in particular, may affect hepcidin levels, but the data, especially for children, are fragmented; (3) pre-HCT hepcidin levels may help predict post-HCT outcomes; (4) there is a need to standardize the determination of hepcidin levels in the clinical setting. We find a very large discrepancy in the reported mean and median hepcidin levels, both in healthy subjects and in AL. This significantly hinders the interpretation and comparison of the results.Objectives: The association between hepcidin and acute leukemia (AL) or hematopoietic cell transplantation (HCT) in children and adults remains obscure. We aimed to assess this potential relationship through a systematic review of observational studies. Methods: An electronic search of three databases, including PubMed, Scopus, and Web of Science Core Collection, was performed up to 31 March 2022. Two independent reviewers assessed the search results according to predetermined inclusion and exclusion criteria, following PRISMA guidelines. Results: Of the 3607 titles identified, 13 studies published between 2008 and 2021 met the inclusion criteria. Most studies included a moderate number of participants and controls and used enzyme-linked immunosorbent assay (ELISA) to determine serum hepcidin levels. The principal findings: (1) serum hepcidin levels in patients with AL or undergoing HCT are increased compared to controls, regardless of the patient’s age and the phase of disease treatment; (2) AL therapy and HCT significantly influence serum hepcidin levels; (3) serum hepcidin may predict a worse outcome in patients with AL and post-HCT. Conclusions: This systematic review provides an overview of observational studies that deal with the association of hepcidin with AL and HCT. Although disturbances in iron metabolism are common in AL and HCT, and hepcidin seems to play a cardinal role in their modulation, more extensive research is needed.

Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia.

Malaria and invasive non-typhoidal Salmonella (NTS) are life-threatening infections that often co-exist in African children. The iron-regulatory hormone hepcidin is highly upregulated during malaria and controls the availability of iron, a critical nutrient for bacterial growth. We investigated the relationship between Plasmodium falciparum malaria and NTS bacteremia in all pediatric admissions aged <5 years between August 1998 and October 2019 (n=75,034). We then assayed hepcidin and measures of iron status in five groups: (1) children with concomitant severe malarial anemia (SMA) and NTS (SMA+NTS, n=16); and in matched children with (2) SMA (n=33); (3) NTS (n=33); (4) cerebral malaria (CM, n=34); and (5) community-based children. SMA and severe anemia without malaria were associated with a 2-fold or more increased risk of NTS bacteremia, while other malaria phenotypes were not associated with increased NTS risk. Children with SMA had lower hepcidin/ferritin ratios (0.10; interquartile range [IQR]: 0.03-0.19) than those with CM (0.24; IQR: 0.14-0.69; P=0.006) or asymptomatic malaria (0.19; IQR: 0.09-0.46; P=0.01) indicating suppressed hepcidin levels. Children with SMA+NTS had lower hepcidin levels (9.3 ng/mL; IQR: 4.7-49.8) and hepcidin/ferritin ratios (0.03; IQR: 0.01-0.22) than those with NTS alone (105.8 ng/mL; IQR: 17.3-233.3; P=0.02 and 0.31; IQR: 0.06-0.66; P=0.007, respectively). Since hepcidin degrades ferroportin on the Salmonella-containing vacuole, we hypothesize that reduced hepcidin in children with SMA might contribute to NTS growth by modulating iron availability for bacterial growth. Further studies are needed to understand how the hepcidin-ferroportin axis might mediate susceptibility to NTS in severely anemic children.

Serum Hepcidin in Children with Inflammatory Bowel Disease.

Hepcidin is a major regulator of iron homeostasis and a mediator of innate immunity. To date, the role of hepcidin in inflammatory bowel disease (IBD) children is not clearly established. We aimed to assess serum hepcidin concentration in IBD children and correlate hepcidin with iron status parameters and inflammatory markers. The study group included 46 pediatric patients with ulcerative colitis and 29 with Crohn's disease. In control group, there were 21 children with functional gastrointestinal disorders. The complete blood count, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, iron, ferritin, transferrin, hepcidin, soluble transferrin receptor, transferrin saturation, and interleukin-6 were measured. The study was approved by the local bioethical committee (KE-0254/22/2013). Mean serum hepcidin concentration was significantly decreased in IBD children (5.98 ng/mL) compared with controls (10 ng/mL) (P = 0.03). Hepcidin did not differ significantly between patients with Crohn's disease (6.9 ± 4.5 ng/mL) and ulcerative colitis (5.4 ± 5.3 ng/mL) (P = 0.07). Hepcidin was significantly decreased in IBD children with iron deficiency (4.9 ± 3.2 ng/mL) compared with healthy controls (10.5 ± 10 ng/mL) (P = 0.02). In anemic children with IBD, serum hepcidin (5.3 ± 4.4 ng/mL) was significantly reduced compared with healthy controls (10.5 ± 10 ng/mL) (P = 0.04), but comparable to nonanemic IBD children (6.6 ± 5.6 ng/mL) (P = 0.62). In IBD, children hepcidin was correlated solely with ferritin (P = 0.007; R = 0.3). In our study, serum hepcidin concentration was significantly decreased in IBD children compared with controls. Hepcidin correlated positively with ferritin, but not with any of inflammatory markers. It may suggest that in our cohort, hepcidin was regulated predominantly by iron storage level.

Pilot study of the effect of cholecalciferol supplementation on hepcidin in children with chronic kidney disease: Results of the D-fense Trial.

Hepcidin is a key mediator of the anemia of chronic kidney disease (CKD). There is emerging evidence that 25-hydroxyvitamin D (25D) regulates hepcidin production. A randomized controlled trial of daily vitamin D supplementation for 12weeks was performed with the aim to test the effects of 4000 versus 400IU of cholecalciferol on serum hepcidin levels in children with non-dialysis CKD recruited at a tertiary care children's hospital. Hepcidin was quantified using a validated competitive enzyme-linked immunosorbent assay. 25D levels were measured using the chemiluminescence Liaison 25(OH)D assay system. Co-variables included hemoglobin, C-reactive protein, ferritin, and serum calcium and phosphorus for safety monitoring. A total of 34 subjects were randomized to either the intervention or control group, of whom 26.5% were female and 23.5% were African American. The mean age of the study cohort was 10.9 [standard deviation (SD) 5.8] years, the mean baseline glomerular filtration rate was 60 (SD 17.6) ml/min/1.73m2, and mean baseline 25D level was 29.7 (SD 11.5) ng/ml. At baseline, 50% of subjects were 25D deficient. There were no significant differences in baseline characteristics between the intervention and control groups. Treatment with 4000IU cholecalciferol was not associated with significant change in hepcidin level at 4 or 12weeks, and multivariable generalized estimating equation regression demonstrated no significant difference in change in hepcidin over the treatment period in either arm. The median C-reactive protein level decreased significantly at 12weeks in the intervention group. These results do not suggest that daily nutritional vitamin D supplementation modifies serum hepcidin levels in children with CKD. Further study will be required to determine whether supplementation may be effective in children with more advanced CKD or those on dialysis.

High-Dose Aspirin is Associated with Anemia and Does Not Confer Benefit to Disease Outcomes in Kawasaki Disease.

BackgroundKawasaki disease (KD) is also known as multiple mucocutaneous lymph node syndrome of systemic vasculitis and is a leading cause of coronary artery lesions (CAL) in childhood. Intravenous immunoglobulin (IVIG) has been proven to effectively reduce the incidence of CAL, but the role and effect dose of aspirin in KD is still unclear. Moreover, overt bleeding and anemia are associated with the use of aspirin, and anemia is common in patients with KD. Thus, the aim of this study was conducted to compare the treatment efficacy, degree of anemia and inflammation, and changes in serum hepcidin in children who received a combination of high-dose aspirin and IVIG in the acute stage of KD, and those who received IVIG alone.Materials and MethodsKD patients from two medical centers were retrospectively analyzed from 1999–2009. All patients were initially treated with a single dose of IVIG (2 g/kg) as the standard care of treatment. In group 1, high-dose aspirin was prescribed (> 30 mg/kg/day) until the fever subsided, and then low-dose aspirin (3–5 mg/kg/day) was prescribed until all the inflammation signs had resolved. In group 2, low-dose aspirin was prescribed without high-dose aspirin. Laboratory data were collected for analysis in both groups.ResultsA total of 851 KD patients (group 1, N = 305, group 2, N = 546) were enrolled in this study. There were no significant differences between group 1 and group 2 in terms of gender (p = 0.51), IVIG resistance rate (31/305 vs. 38/546, p = 0.07), CAL formation (52/305 vs. 84/546, p = 0.67), and duration of hospitalization (6.3 ± 0.2 vs. 6.7 ± 0.2 days, p = 0.13). There were also initially no significant differences in total white blood cell count, hemoglobin level, platelet count, and CRP before IVIG treatment between groups (all p>0.1). After IVIG treatment, group 1 had significantly lower levels of hemoglobin (p = 0.006) and higher CRP (p<0.001) as well as a smaller decrease in CRP level (p = 0.012). Furthermore, there was also a higher serum level of hepcidin and a delayed decrease in hepcidin level after receiving IVIG in group 1 (p = 0.04 and 0.02, respectively).ConclusionsThese results provide evidence demonstrating that high-dose aspirin in the acute phase of KD does not confer any benefit with regards to inflammation and it does not appear to improve treatment outcomes. Therefore, high-dose aspirin is unnecessary in acute phase KD.

Serum hepcidin: indication of its role as an “acute phase” marker in febrile children

BackgroundHepcidin is classified as a type II acute phase protein; its production is a component of the innate immune response to infections.ObjectiveTo evaluate the alterations of serum hepcidin in children during and following an acute febrile infection.Materials and methods22 children with fever of acute onset (< 6 hours) admitted to the 2nd Department of Pediatrics-University of Athens. Based on clinical and laboratory findings our sample formed two groups: the viral infection group (13 children) and the bacterial infection group (9 children). Hepcidin, ferritin and serum iron measurements were performed in all subjects.ResultsSerum hepcidin values did not differ notably between children with viral and bacterial infection, but a significant reduction of hepcidin was noted in both groups post-infection.ConclusionOur study provides clinical pediatric data on the role of hepcidin in the face of an acute infection. In our sample of children, hepcidin was found to rise during the acute infection and fall post-infection.

772 Serum Hepcidin in Children with Beta-Thalassemia

BackgroundHepcidin, first described about 10 years ago, is a key iron - regulatory hormone. However, hepcidin measurement in a variety of human disease states are still lacking.AimTo study serum level...

Increased Serum Hepcidin in Children with Infection and Correlation with Ferritin Level.

Background and aims: Hepcidin is a recently discovered peptide produced by hepatocytes and macrophages in response to inflammatory stimuli. It is markedly induced during inflammation. There are only limited data on hepcidin regulation during systemic acute inflammation in children. The aim of this study was to assess the serum concentration of hepcidin in children with bacterial and viral infection and to correlate it with ferritin levels. Methods: 69 children (43 boys) (mean age 28.94 ±29.69 months) were enrolled into the study. Blood was drown for the measurement of hepcidin in 50% of patiens on the first and second day of fever and in 50% on the third day. 69 healthy children were used as control population. Hepcidin was measured using Elisa method. Results: A significant increase in serum hepcidin was observed in children with acute infection (85.25± 43.42 pg/ml ) compared with serum hepcidin of contrlols (50.11± 28.71 pg/ml), P< 0.001. Concentrations of hepcidin correlated positively with serum ferritin levels ( P< 0.01). Conclusions: Hepcidin is a new peptide that increases during inflammation. In children with infections, hepcicin production is increased. Its correlation with ferritin levels could propose a new role for hepcidin, the one of acute phase reactant protein although further investigation is needed in order to clarify whether there is difference between bacterial and viral infections.