Serum Hepcidin Levels Research Articles

Changes in iron metabolism centered on hepcidin due to high-intensity exercise under restricted food intake

ObjectivesThe purpose of this study was to observe changes in iron metabolism of rats due to high-intensity exercise during reduced food intake. MethodsThirty-six, 4-wk-old male Wistar rats were divided into six groups after being acclimated to running: rested control, intense exercise, 80% feeding and rested, 80% feeding and intense exercise, 70% feeding diet and rested, and 70% feeding and intense exercise groups. Only three intense exercise groups underwent acute running sessions for 30 min (30 m/min) once a day for 7 d. ResultsRats did not develop anemia with exercise and food intake restriction. Serum iron levels, transferrin saturation, hepcidin-25, and hepatic iron levels in the exercise groups were lower than those in the respective resting groups. However, these values in the 70% diet groups were slightly higher than those in the 80% diet groups. Serum erythropoietin levels decreased as food intake decreased, but the serum erythropoietin level in the 70% feeding and intense exercise group was similar to that in the rested control group. Serum interleukin-6 levels were significantly lower in the groups with restricted food intake than in the free-fed group, and exercise had no effect. ConclusionsHigh-intensity exercise under restricted food intake may significantly alter the iron metabolism to maintain blood cell levels due to the strong promotion of metabolic iron utilization in response to dietary iron depletion, increased iron demand, and excretion.

Association of Serum Hepcidin Levels with Aerobic and Resistance Exercise: A Systematic Review.

Background: Prevalence of iron deficiency is commonly reported among athletic population groups. It impairs physical performance due to insufficient oxygen delivery to target organs and low energy production. This is due to the high demand of exercise on oxygen delivery for systemic metabolism by the erythrocytes in the blood. Hepcidin, the key regulator of iron homeostasis, decreases to facilitate iron efflux into the circulation during enhanced erythropoiesis. However, acute anaemia of exercise is caused by increased hepcidin expression that is induced by stress and inflammatory signal. The study aimed to systematically review changes in serum hepcidin levels during resistance and aerobic exercise programmes. Methods: A systemic literature search from 2010 to April 2020 across seven databases comprised of Cochrane library, PubMed, Web of Science, Scopus, Embase, MEDLINE, and OpenGrey. The primary outcome was increased or decreased serum hepcidin from baseline after the exercise activity. Risks of bias were evaluated by using the National Institutes of Health (NIH) for quality assessment of before and after different exercise programmes. Results: Overall, twenty-three studies met the inclusion criteria. Out of the 23 studies, 16 studies reported significantly exercise-induced serum hepcidin elevation. Of the 17 studies that evaluated serum interleukin (IL)-6 levels, 14 studies showed significant exercise-induced serum IL-6 elevation. Changes in exercise-induced serum hepcidin and IL-6 levels were similar in both resistance and endurance exercise. Significant correlations were observed between post-exercise hepcidin and baseline ferritin levels (r = 0.69, p < 0.05) and between post-exercise hepcidin and post-exercise IL-6 (r = 0.625, p < 0.05). Conclusion: Resistance and endurance training showed significant increase in serum hepcidin and IL-6 levels in response to exercise. Baseline ferritin and post-exercise IL-6 elevation are key determining factors in the augmentation of hepcidin response to exercise.

Molecular analysis of homeostatic iron regulator, transmembrane protease serine-6, and BTB domain-containing protein-9 variants and iron parameters in blood donors

Genetic variants associated with iron homeostasis have been identified, but their association with iron-related indices and variables among different ethnic populations remains controversial. We aimed to explore the genotype frequency and allelic distribution of three iron-metabolism related variants in homeostatic iron regulator gene (HFE; rs1800562 G/A), transmembrane protease, Serine-6 gene (TMPRSS6; rs855791 A/G), and BTB domain-containing protein-9 gene (BTBD9; rs9357271 C/T) among a sample of the Middle Eastern blood donors and to detect the association of these variants on blood indices, and serum hepcidin/ferritin levels. Real-Time TaqMan genotyping assay for the specified variants was applied for 197 unrelated blood donors. Complete blood picture and serum hepcidin/ferritin levels were assessed. All participants were carriers of rs1800562*G/G genotype for HFE. The frequency of A/A and A/G genotypes of TMPRSS6 rs855791 variant was 55% and 45%, and for C/C, C/T, and T/T of BTBD9 rs9357271, were 15%, 43%, and 42%, respectively. Minor allele frequencies of rs855791*G and rs9357271*C were 0.23 and 0.37. The GGC genotype combination (for HFE/TMPRSS6/BTBD9, respectively) was more frequent in male participants. Higher serum hepcidin and hepcidin/ferritin ratio were observed in TMPRSS6 (A/G) carriers. While subjects with BTBD9 C/T and TT genotypes had lower serum ferritin values and higher levels of hepcidin and hepcidin/ferritin ratio compared with C/C genotype. No significant associations were found with any other blood parameters.In conclusion, TMPRSS6 rs855791 (A/G) and BTBD9 rs9357271 (C/T) variants were prevalent in the present blood donor population and may influence the serum hepcidin and/or ferritin levels.

Relationship between serum hepcidin levels and cardiovascular disease in patients with maintenance hemodialysis.

To investigate the serum level of hepcidin and its relationship with cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients. Blood was obtained from 75 MHD patients before undergoing hemodialysis and 20 healthy controls. Serum hepcidin, advanced oxidation protein products (AOPP) and interleukin (IL)-6 were measured by enzyme-linked immunosorbant assay (ELISA). Spearman correlation, and binary logistic regression linear regression analyses were used to assess the relationship between serum hepcidin and other parameters. The serum level of hepcidin, AOPP and IL-6 was significantly up-regulated in MHD patients compared with the control (P < 0.05). Furthermore, serum hepcidin levels in patients with CVD were higher than those in patients without CVD (P < 0.05). In all MHD patients, serum hepcidin level was correlated positively with erythropoietin (EPO) dose per week (ρ = 0.251, P = 0.030), EPO resistance index (ρ = 0.268, P = 0.020), ferritin (ρ = 0.814, P < 0.001), transferin saturation (TSAT, ρ = 0.263, P = 0.023), AOPP (ρ = 0.280, P = 0.049), high sensitive C reactive protein (ρ = 0.151, P = 0.006), IL-6 (ρ = 0.340, P = 0.003) and left ventricular mass index (LVMI, ρ = 0.290, P = 0.033). Moreover, it was negatively correlated with serum pre-albumin (ρ = -0.266, P = 0.021), total iron-binding capacity (TIBC, ρ = -0.458, P < 0.001), unsaturated iron-binding capacity (UIBC, ρ = -0.473, P < 0.001) and transferrin (ρ = -0.487, P < 0.001). Linear regression analysis showed that ferritin (β = 0.708, P < 0.001), TIBC (β = -0.246, P = 0.032) and IL-6 (β = 0.209, P = 0.041) were independently associated with hepcidin. Results of binary logistic regression analysis suggested that higher serum hepcidin level (>249.2 ng/mL) was positively and independently related to CVD (OR = 1.32, 95% CI [1.20-9.56], P = 0.043). Serum hepcidin level is associated with CVD in MHD patients, indicating that hepcidin may be a novel biomarker and therapeutic target for CVD.

Perinatal and early-life cobalt exposure impairs essential metal metabolism in immature ICR mice

The objective of the present study was to assess the impact of cobalt (Co) exposure on tissue distribution of iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn), as well as serum hepcidin levels in immature mice (18, 25, 30 days). Pregnant mice were exposed to 75 mg/kg b.w. cobalt chloride (CoCl2 × 6H2O) with drinking water starting from 3 days before delivery and during lactation. At weaning (day 25) the offspring were separated and housed in individual cages with subsequent exposure to 75 mg/kg b.w. CoCl2 until 30 days postnatally. Evaluation of tissue metal levels was performed by an inductively coupled plasma-mass spectrometry (ICP-MS). Serum hepcidin level was assayed by enzyme linked immunosorbent assay (ELISA). Cobalt exposure resulted in a time- and tissue-dependent increase in Co levels in kidney, spleen, liver, muscle, erythrocytes, and serum on days 18, 25, and 30. In parallel with increasing Co levels, CoCl2 exposure resulted in a significant accumulation of Cu, Fe, Mn, and Zn in the studied tissues, with the effect being most pronounced in 25-day-old mice. Cobalt exposure significantly increased serum hepcidin levels only in day18 mice. The obtained data demonstrate that Co exposure may alter essential metal metabolism in vivo.

Relation of Serum Ferritin Level with Serum Hepcidin and Fucose Levels in Children with β-Thalassemia Major

The aim of this study was to assess serum ferritin, hepcidin, L-fucose, and protein binding fucose levels in β-thalassemia major (β-TM) patients and to correlate the serum ferritin level with hepcidin and fucose levels. A total 70 (26 males and 44 females) children with β-TM, ages ranging from 5 to 16 years (mean age 8.3 ± 2.7 years) and 50 (25 males and 25 females) apparently healthy subjects with matching age and sex were included as a control group. An especially designed questionnaire was used to collect age, gender, body mass index (BMI), hemoglobin (Hb), serum ferritin, hepcidin-25 peptide, α-L-fucose, and protein binding fucose (PBF) levels. β-Thalassemia major patients had significantly (p < 0.05) higher serum ferritin, fucose and PBF levels, but the serum hepcidin level was significantly (p < 0.05) lower when compared to the controls, and their levels were affected by the gender of the β-TM patients, as it was significantly (p < 0.05) higher in female in comparison to male patients. There was no significant (p > 0.05) correlation between serum ferritin with hepcidin and fucose levels as a marker of iron overload in β-TM. The regulation of hepcidin, and L-fucose levels in patients with β-TM is more affected by erythropoeitic activity than by iron overload, as there was no significant correlation between serum ferritin with hepcidin and fucose levels as a marker of iron overload in β-TM.

Hepcidin Levels and Pathological Characteristics in Children with Fatty Liver Disease.

PurposeHepcidin levels have previously been reported to be correlated with liver damage. However, the association between hepcidin levels and liver fibrosis in children with fatty liver disease remains unclear. This study therefore aimed to investigate the pathophysiology of fibrosis in children with fatty liver disease and its association with hepcidin levels.MethodsThis retrospective case series included 12 boys aged 6–17 years who were diagnosed with nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) at the Tokyo Medical University Hospital. Sixteen liver biopsy samples from 12 subjects were analyzed. Serum hepcidin levels were assayed using enzyme-linked immunosorbent assay. Immunostaining for hepcidin was performed, and the samples were stratified by staining intensity.ResultsSerum hepcidin levels were higher in pediatric NAFLD/NASH patients than in controls. Conversely, a significant inverse correlation was observed between hepcidin immunostaining and Brunt grade scores and between hepcidin scores and gamma-glutamyltranspeptidase, hyaluronic acid, and leukocyte levels. We observed inverse correlations with a high correlation coefficient of >0.4 between hepcidin immunostaining and aspartate aminotransferase, alanine aminotransferase, total bile acid, and platelet count.ConclusionThere was a significant inverse correlation between hepcidin immunoreactivity and fibrosis in pediatric NAFLD patients; however, serum hepcidin levels were significantly higher, suggesting that these patients experienced a reduction in the hepcidin-producing ability of the liver in response to iron levels, leading to subsequent fibrosis. Therefore, hepcidin levels can be used as markers to identify the progression of fibrosis in patients with NAFLD.

Clinical and Experimental Study of Low Molecular Weight Heparin in Patients with Chronic Anemia

Objective: To preliminary study the significance of low molecular weight heparin (LMWH) in the treatment patients of with anemia of chronic diseases (ACD), and the changes in the serum levels of BMP6, hepcidin and IL-6. To preliminary study the significance of low molecular weight heparin (LMWH) in the treatment the patients with anemia of chronic diseases (ACD), and the changes in the serum levels of BMP6, hepcidin and IL-6. Methods: Used LMWH (4000 u/day, 7 - 15 days) to therapy 61 patients with ACD, and ELISA method was used to determine Hepcidin and BMP6 before and after treatment, and the determination of IL-6 by Electro-chemi-luminescence, and to analyze its clinical significance. Results: 1) In all 61 cases, the levels of Hepcidin in post-therapy were 0.82 ± 0.24 mg/L, which were lower than 1.05 ± 3.83 mg/L in pre-therapy (t = 2.5726, P P P > 0.05). However, The levels of Hb in post-therapy were higher than in pre-therapy (t = 1.9832, P P P P P > 0.05). 5) Although Hb level increased slightly in the non-tumor anemia group, there was no statistical significance (P > 0.05), and there was no statistical difference in other indexes (all P > 0.05). 6) After treatment, the level of Hb was negatively correlated with Hepcidin and IL-6 (respectively r = -0.2809, t = 2.2490, P P P < 0.05). There was no correlation between BMP6 and Hb, Hepcidin and IL-6 levels. Conclusion: LMWH could up-regulate the levels of Hb, and better for the degree of anemia in patients with ACD. The possible mechanism is to reduce the level of Hepcidin and IL-6.

Hepcidin Status among Iron Deficient Anemic Pregnant Women in Gaza strip: A Case Control Study

Background: Hepcidin, a peptide hormone composed of 25 amino acids. Hepcidin is synthesized mainly in the liver. Iron deficiency anemia (IDA) is common during pregnancy and is associated with higher maternal morbidity and mortality in Gaza strip. Understanding of hepcidin hormone and its role in iron metabolism could lead to a new sensitive indicator for earlier detection of cases with IDA. Objective: To assess hepcidin status among IDA pregnant women and its relationship with some biochemical variables in Gaza strip. Materials and methods: A case control study comprised 45 IDA pregnant women and 45 apparently healthy pregnant women. Questionnaire interviews were applied among the study population. Serum hepcidin and ferritin were measured by Enzyme-linked immunosorbent assay (ELISA), iron and total iron binding capacity (TIBC) were determined photometrically. Complete blood count (CBC) was also performed. Transferrin and transferrin saturation were calculated. An approval was obtained from Helsinki committee and ministry of health to conduct this study. Overall data were computer analyzed using SPSS (Ver. 18). Results: The mean levels of serum hepcidin, iron, transferrin saturation, and ferritin in cases were significantly lower compared to those of controls (2.6±4 ng/ml, 63.2±25.3 µg/dl, 15.6±8.0% and 8.0±9.7 ng/ml versus 7.5±7.3 ng/ml, 77.7±22.9 µg/dl, 23.5±8.0% and 15.4±14.3 ng/ml respectively with P=0.000). The Pearson correlation test showed that positive significant correlations between hepcidin levels and serum iron, ferritin, and transferrin saturation (P&lt;0.001). On the other hand, negative significant correlations were showed with TIBC and transferrin (P&lt;0.001). Conclusions: Serum hepcidin level has a relationship with anemia among pregnant women. Therefore, monitoring of hepcidin levels can play an important role in management of anemia among pregnant women.

The Hepcidin and 25-OH-Vitamin D Levels in Obese Children as a Potential Mediator of the Iron Status.

Obesity is associated with the risk factors such as iron and vitamin D deficiencies. Increased risk of iron deficiency generally correlates with the high levels of serum hepcidin in obese children. Vitamin D deficiency was also linked to an increase in serum hepcidin levels. We aimed to compare iron parameters and investigate the hepcidin levels in obese and non-obese children. This study included 83 children and adolescents including obese (n = 35) and non-obese (n = 48). Laboratory values including serum iron levels, total iron-binding capacity, percentage of transferrin saturation, ferritin, reticulocyte parameters and high sensitivity C-reactive protein (hsCRP), hepcidin, 25-OH-Vitamin D were measured. Average levels of hepcidin, hsCRP, and ferritin were found to be similar in both study groups. Serum iron levels, total iron-binding capacity, percentage of transferrin saturation, and 25-OH-vitamin D levels were significantly lower in the obese group. There was no statistically significant difference between hepcidin and 25-OH-vi-tamin D levels. Average hepcidin levels were detected to be similar in both groups (p = 0.580) whereas, 25-OH-vi-tamin D levels were significantly lower in the obese group (p < 0.001). A statistically negative correlation was observed between average BMI (body mass index) and serum iron level (r = -0.476; p < 0.001), BMI and transferring saturation (r = -0.467; p < 0.001), and BMI and 25-OH-vitamin D levels (r = -0.474; p < 0.001). Hence, no statistically significant relation was detected between hepcidin and 25-OH-vitamin D levels (r = 0.233; p = 0.084). Being female, vitamin D deficiency, and IRF (%) (Immature Reticulocyte Fraction) were found as independent risk factors for BMI increase due to logistic regression analyses. In conclusion, observed statistical associations and correlations do not prove a causal relationship between the hepcidin levels and iron deficiency but vitamin D deficiency seems likely to cause high BMI levels or in contrast, obesity may cause vitamin D deficiency in the children. No association was found between hepcidin, ferritin, and hsCRP levels with obesity in children. However, vitamin D deficiency was detected to cause a 5.3-fold increase in BMI levels. We suggest that there may be different mechanisms in obesity-related metabolic and hematological events. One can also envision that there is not enough time for the chronic inflammation processes to develop during childhood as opposed to those frequently seen in adult obese individuals.

Assessment of Some Hematological parameters in Iraqi Women with Different Breast Cancer Stages

Breast cancer (BC) is the most commonly diagnosed cancer in women. The metabolism of iron is closely regulated by hepcidin which exerts its action by interacting with a ferroportin.&#x0D; The aim of the present study was to assess the alterations in the levels of some serum biomarkers that have a role in iron homeostasis (hepcidin and ferroportin) in addition to hematological parameters (hemoglobin, leukocyte and platelets count) in different stages of BC.&#x0D; This study included 66 women with BC. The patients were categorized as follows : group 1 includes :22 patients with stage I disease ,group 2 includes: 22 patients with stage II disease ,and group 3 include: 22 patients with stage III disease .Group 4 includes :22 apparently healthy women as control.&#x0D; Data analysis revealed a significant elevation of serum hepcidin levels of patients groups 1, 2, and 3 (437.2±26.4, 501.4±31.8 and 558.5±21.3 pg/ml respectively) ,vs (179.4±19.8 pg/ml) of control, with steady elevations from stage I to III . Furthermore, serum ferroportin levels were significantly lowered in groups 1 and 3 compared to control (0.589±0.107 and 0.733±0.1 vs 1.37±0.28 ng/ml respectively).While blood hemoglobin level of group 3 were lower (11.96±0.18 vs 12.7±0.13g/dl ) compared with controls . Blood leukocyte count of patients (all groups) (7.39±0.28 ,8.93±0.48,9.86±0.52 (^103/µl) respectively) were markedly increased compared to controls (6.06±0.23), while mean platelet count for patients in group 2&amp;3 were significantly increased compared to controls (313.9±19.3,309.2±25.3 vs 233.3±9.1 respectively).&#x0D; In conclusion, hepcidin, ferroportin and hematological markers including hemoglobin, WBC count and platelets count are altered in women with BC compared to healthy control. The changes occur mostly in accordance with disease stages.

Changes in Hepcidin Serum Levels Correlate with Clinical Improvement in Idiopathic Restless Legs Syndrome Patients

Background: Restless legs syndrome (RLS) is a common sensory motor neurological disorder that is related to iron–dopamine dysregulation and immune system alteration. We aimed to assess the effects of serum hepcidin, an iron-regulating hormone, in drug-naive RLS patients compared to healthy controls and to evaluate its role in helping to predict clinical improvement after treatment with dopamine agonist. Methods: Nonanemic and drug-naive RLS patients (n = 18) and healthy controls (n = 15) were enrolled. The serum hepcidin and iron-related values in the serum were measured upon the first visit in both groups and 12 weeks later after dopaminergic treatment in 12 patients. Information about sociodemographic characteristics, sleep-related profiles, mood and anxiety was obtained upon the first visit in all participants as well as after treatment in RLS patients. Results: Serum hepcidin levels exhibited no significant differences between patients with drug-naïve RLS and healthy controls at diagnosis (7.1 ± 2.4 vs. 7.0 ± 3.2 ng/mL, p = 0.357). Decreased hepcidin levels were significantly associated with decreased RLS severity (β = 0.002, 95% CI = 0.00−0.00, p = 0.005) and improved quality of life (β = 0.002, 95% CI = 0.00−7.01, p = 0.044) in a dose-dependent manner after 12 weeks of treatment with a dopamine agonist. This association was independent of age, sex, inflammatory markers, sleep quality, insomnia, daytime sleepiness, depression and anxiety. Conclusions: This study demonstrates the role of hepcidin in evaluating the positive therapeutic response in RLS.

Time to Start Delivering Iron Chelation Therapy in Newly Diagnosed Severe β-Thalassemia.

Background Iron overload is still a major complication of severe β-thalassemia. Indication to start iron chelation therapy is based on serum ferritin (SF) or transferrin saturation (TS) level or the amount of transfusion. The goal of this study is to analyse the pattern of iron status, the amount of transfusion regarding the time to start iron chelator, and serum hepcidin levels in newly diagnosed severe β-thalassemia. Methods A prospective cohort study was performed at Hasan Sadikin General Hospital on newly diagnosed severe β-thalassemia patients. Subjects had not received any blood transfusion with normal liver function test, CRP, and IL-6 levels who consumed normal diet according to age. The SF and TS levels indicate iron status, while hepcidin level indicates iron regulator status. Main indicator to start iron chelation therapy when SF level ≥1.000 ng/mL, TS level ≥70%, or after receiving transfusion at least 10 times. Statistical analysis used Mann–Whitney and Spearman. Results Forty-two newly severe β-thalassemia, 30 (71.4%), were diagnosed before 1 year old, mean 9.9 ± 6.4 months, range 2–24 months. Range amount of transfusion until SF level reached ≥1,000 ng/mL were 4-12 times, mean 7 ± 2 times. Mean SF and TS level at diagnosis were 365.6 ± 194.9 ng/mL and 67.3 ± 22.5%, while hepcidin level was normal, mean 242.6 ± 58 ng/mL. 36/42 patients have reached SF >1000 ng/mL with amount of transfusion less than 10 times. There was no significant difference of SF, TS, and hepcidin levels when SF >1000 ng/mL in the group with amount of transfusion 7–12 and less than 7 (p = 0.454, p = 0.084, p = 0.765), respectively. A significant positive correlation between SF and amount of transfusion was observed (p < 0.001; r = 0.781). Conclusion Iron overload in severe β-thalassemia patients might occur earlier even before they received 10 times transfusion. Hepcidin serum level tends to increase when iron overload just started.

Severity of clinical manifestation, and prognosis of patients with myelofibrosis

Introduction: Primary myelofibrosis (PMF) is a myeloproliferative disorder characterized by bone marrow fibrosis and ineffective extramedullary hematopoiesis, which presents with anemia, constitutional symptoms, and excessive splenomegaly. A number of factors are involved in the pathogenesis of the anemia in PMF, including impaired iron metabolism regulation. It was found that higher levels of the key regulator of iron metabolism - the peptide hormone hepcidin in patients with PMF, are associated with the severity of the anemia, blood transfusion dependence and decreased overall survival. Aim: The aim of the study was to analyze the serum levels of hepcidin in patients with PMF and its impact on the clinical course, prognosis, and outcome of the disease. Materials and Methods : A total of 68 patients with PMF and 12 healthy controls were analyzed. Serum hepcidin levels were measured by ELISA. The results were statistically analyzed by dispersion, comparison, and correlation methods. Results: Then mean hepcidin levels in patients with PMF were statistically significantly higher compared to healthy controls. (99.05 ng/mL; 20.57 ng/mL; F = 7.95; p = 0.006). High levels of hepcidin correlated with high risk according to DIPSS (p = 0.046), carrier of JakV617F mutation (p = 0.022), fibrotic phase according to WHO 2016 (p = 0.062), and the number of blood transfusions per month (p = 0.005). Higher hepcidin levels were not relevant to overall survival. Conclusion: Hepcidin is a biological marker the monitoring of which in the course of MF would help for a more accurate clinical and prognostic assessment of the disease.

Correlation of Maternal Serum Hepcidin, Soluble Transferrin Receptor (sTfR) and Cholecalciferol with Third Trimester Anemia: Findings from A Nested Case-control Study on A Pregnancy Cohort

BACKGROUND: Cholecalciferol, hepcidin, and soluble transferrin receptor (sTfR) interaction play an essential role in iron hemostasis. Anemia in pregnancy contributes to morbidity and mortality both for the mother and baby. In this study, we assessed the correlation between hepcidin, sTfR and cholecalciferol in third trimester maternal anemia. We aimed to find the cut-off for hepcidin and sTfR.METHODS: A case-control study involving 56 pregnant women in each anemia and healthy group was nested on a previous larger cohort study in Indonesia. Serum hepcidin, sTfR and cholecalciferol level were measured by enzyme-linked immunosorbent assay (ELISA) method.RESULTS: Serum hepcidin and sTfR level were significantly higher in case group, while serum cholecalciferol level has no difference between the two groups. New cut-off points were found for hepcidin (&lt;15.93 ng/mL) and sTfR level (&gt;2234.45 ng/mL). Low level of hepcidin (OR=5.32) and high level of sTfR (OR=8.28) increase the risk of anemia. High level of sTfR (adjusted OR=4.725; CI 95%=1.730-12.904; p=0.02) was the most important factor contributes to anemia, followed by the low level of hepcidin (adjusted OR=3.677; CI 95%=1.363-9917; p=0.01).CONCLUSION: The high level of sTfR is the most important factor related to anemia in the third trimester, followed by the low level of hepcidin. Low cholecalciferol level tends to favor the incident of anemia. The new cut-off point of third trimester sTfR and third trimester hepcidin were established in this study and may be useful for risk assessment and treatment monitoring for anemia in pregnancy.KEYWORDS: anemia, cholecalciferol, hepcidin, pregnancy, soluble transferrin receptor

Hepcidin Is a Reliable Marker of Iron Deficiency Anemia in Newly Diagnosed Patients with Inflammatory Bowel Disease.

Results There was a high statistically significant difference between IBD patients and controls in levels of hepcidin (P < 0.01). Namely, serum hepcidin levels were significantly higher in the control group. There was no statistically significant correlation of serum hepcidin with CRP, Mayo score, or CDAI, respectively (P > 0.05). However, we have found a statistically significant negative correlation of sTfR and TIBC with hepcidin (P < 0.01). Conclusion Results of our study suggest that hepcidin is a reliable marker of IDA in patients with IBD, and it could be used in routine clinical practice when determining adequate therapy in these patients.

Characterization of INCB00928, a Potent and Selective ALK2 Inhibitor for the Treatment of Anemia

A significant population of patients with myelofibrosis (MF) develop anemia and either require red blood cell (RBC) transfusions or have an inadequate response to the currently available therapies and become transfusion-dependent. In patients with MF, elevated levels of serum hepcidin, a key iron regulatory hormone, is associated with increased dependence on RBC transfusions and reduced overall survival. Elevated hepcidin expression has also been observed to cause severe functional iron deficiency anemia and is central to the pathophysiology of anemia of chronic disease. Thus, to ensure proper maintenance of iron homeostasis, hepcidin levels are tightly regulated. Specifically, the production of hepcidin is controlled by the bone morphogenetic protein (BMP) type I receptor ACVR1, a gene that encodes the serine/threonine kinase ALK2. In preclinical models, knockdown or complete loss of ALK2 decreases hepcidin production resulting in elevated serum iron levels. In this study, we report characterization of INCB00928, a novel small molecule inhibitor of ALK2 for the treatment of anemia. INCB00928 was observed to have subnanomolar activity against ALK2 and selectivity over ALK1 and ALK3 in biochemical enzyme assays. In cell-based profiling studies, INCB00928 inhibited ALK2 potently and selectively over ALK1 and ALK3 as determined by the inhibition of ligand-induced SMAD pathway signaling. Importantly, in both an immortalized human liver cell line as well as primary human hepatocytes, INCB00928 inhibited BMP-induced production of hepcidin with nanomolar activity. INCB00928 was also observed to have suitable absorption, distribution, metabolism, and excretion properties to be dosed in in vivo rodent studies. In tumor- and inflammation-induced mouse models of anemia, INCB00928 improved RBC count, hemoglobin, and hematocrit levels while decreasing hepcidin levels in a dose-dependent manner. Additionally, consistent with the improved symptoms of anemia, pSMAD1/5 inhibition was observed in a dose-dependent manner in liver tissues collected from INCB00928-treated mice. In summary, INCB00928 is a potent, selective, and orally available small molecule inhibitor of ALK2, which significantly reduces the production of hepcidin in human liver cells, primary hepatocytes, and in rodent models of anemia. For the majority of patients with MF, the management of anemia remains an unmet need. The preclinical findings from this study suggest ALK2 kinase inhibition with INCB00928 may be a promising novel treatment to reduce the production of hepcidin and improve MF-related anemia in humans, thus warranting further investigation. Disclosures Chen: Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Stubbs:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Pusey:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Wen:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Collins:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Kapilashrami:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Rupar:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Thekkat:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Lin:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Bowman:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Yang:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Diamond:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Yeleswaram:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Kim:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Koblish:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Chen:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Wee:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company.

A Phase 1/2 Study of INCB000928 As Monotherapy or in Combination with Ruxolitinib in Patients with Anemia Due to Myelofibrosis (INCB 00928-104)

A Phase 1/2 Study of INCB000928 As Monotherapy or in Combination with Ruxolitinib in Patients with Anemia Due to Myelofibrosis (INCB 00928-104)

Factors Associated with the Platelet Graft in Hematopoietic Precursor Cell Transplant Patients in a Third Level Hospital in Mexico

Factors associated with the platelet graft in hematopoietic precursor cell transplant patients in a third level hospital in Mexico Introduction The success of TCPH is affected by various factors such as graft versus host disease (GVHD), relapse, treatment-related toxicity, and infection, leading to increased morbidity and mortality. Thrombocytopenia is almost universal in the pre-graft period in patients sometimes on TCPH, delayed platelet recovery beyond the expected time occurs in 5% to 37% of patients sometimes on TCPH. Various studies have described a relationship between platelet graft delay and CD34 + cell dose, pre-transplant disease status, source of the graft, blood group, and even the development of platelet refractoriness. Male receptor gender and elevated serum hepcidin level have also been associated as risk factors for delayed platelet graft. Aims To assess the factors associated with late platelet grafting in the post-transplant patient of hematopoietic precursor cells. Methods Retrospective, cross-sectional, observational and descriptive study. From January 2018 to December 2019. Results 101 patients were included, 59.4% men and 40.6% women. The mean age was 37 years. Patients diagnosed with MM were 24.8%, ALL 22.8%, NHL 19.8%, HL 15.8%, AML 14.9%, CML 1%. 73.3% of the patients had a CR prior to transplantation and 26.7% had a PR. BUCY was used as a conditioning scheme in 27.7%, PEAM 27.7%, FLUBUCY 16.8%, BORMEL 11.9%, BUMEL 9.9%. 55.4% of the patients underwent autologous transplantation and 44.6% underwent allogeneic. During the peritransplantation period, 32.7% had some type of infection, 21.8% developed GVHD, and 12.9% had a relapse of the disease. Of the 101 patients, 85.1% were alive at the time of this study; 3 of these patients did not achieve a platelet graft, 2 of them required a thrombopoietic receptor agonist, 2 had a diagnosis of ALL and one had MM, the 3 patients died before the +100 day due to infectious complications. The mean platelet apheresis transfusion was 1.80. The mean recovery time for neutrophils was 11 days and for platelets 13 days. The mean follow-up was 25 months. The overall one-year survival is 70% in allogeneic post-transplant patients and 95% in autologous post-transplant patients Of the factors evaluated using the KM method to relate them to overall survival, statistical significance was found: relapse (p = 0.0001), GVHD (p = 0.002) and more than 5 x 106CD34 infused (p = 0.047). The recovery time for the platelet and neutrophil graft was not statistically significant, p=0.288 and p = 0.421 respectively. GVHD was the only factor associated with relapse-free survival. When performing a bivariate analysis, the factors with statistical significance (p= &amp;lt;0.05) related to the platelet graft were: allogeneic transplantation, the amount of CD34 infused, infections and GVHD. Discussion The mean time for neutrophil and platelet grafting was 11 and 13 days, respectively. According to the bivariate analysis performed, allogeneic transplantation confers 6.7 times more risk for the platelet graft to be greater than 13 days p= 0.0001. Begeman et al. have reported that there is an inverse relationship between the amount of CD34 infused and the time of platelet grafting. This observation was not reproducible in our population since we found that an amount greater than 5 x 106 CD34 conferred a 4.4-fold risk for the platelet graft to be greater than 13 days, with a p= 0.0001. This could suggest that it is probable that an amount greater than 5 x 106 could have an opposite effect and prolong the grafting time; this will have to be taken with reserve since in our multivariate a significant result was not confirmed. Overall survival and relapse-free survival were not affected by neutrophil or platelet graft time as described in some studies; probably due to the size of our sample and that in other series the follow-up time has been comparable. The median of relapse-free survival was reached at 5 months and it should be noted that relapse was the only factor that had a negative impact on the survival of our population, and was observed only in patients undergoing allogeneic transplantation; therefore, those patients who present a relapse of the disease have a poor prognosis, whose median was reached at 25 months, so perhaps it would be worthwhile to search for available rescue therapies in these patients. Disclosures No relevant conflicts of interest to declare.

Relation of serum hepcidin levels and restless legs syndrome in chronic hemodialysis patients.

Iron deficiency anemia, pregnancy, and end-stage renal disease (ESRD) are common causes of secondary restless legs syndrome (RLS). Serum ferritin is considered the most specific test associated with the total amount of body iron stores. However, due to the increase of serum ferritin secondary to inflammation in chronic hemodialysis (HD) patients, serum ferritin test results do not fully reflect decreased iron stores in these patients. The present study evaluates the serum hepcidin levels, as the main regulator of iron metabolism, and its relationship with RLS in chronic HD patients. The present cross-sectional study involved 72 patients (36 with and 36 without RLS) who received chronic HD treatment between April 2014 and April 2015. Demographic and biochemical data were evaluated in all patients, and statistical analyses were performed. The mean age and mean dialysis vintage of all patients (56% women) included in the study were 65.3 ± 11.6years and 41.5 ± 36.5months, respectively. Serum hepcidin, hemoglobin A1C (HbA1C), and ferritin levels were significantly higher in patients with RLS (p= 0.001, p =0.032, p =0.042, respectively). In addition, a positive correlation was found between International Restless Legs Syndrome Study Group severity scale score and serum hepcidin levels, HbA1C, and ferritin (r =0.387, p =0.001; r =0.426, p =0.034; r =0.240, p =0.046, respectively). A multivariate linear regression analysis revealed hepcidin and HbA1C to be independently associated with the presence of RLS. A significant relationship was detected between RLS and increased serum hepcidin levels in chronic HD patients, and uncontrolled diabetes was noted to contribute to this association.