Serum Hepcidin Levels In Patients Research Articles

ALK2 and JAK2 Inhibition for Improved Treatment of Anemia in Myelofibrosis Patients: Preclinical Profile of an ALK2 Inhibitor Zilurgisertib in Combination with Ruxolitinib

Introduction: Anemia is a common occurrence in patients with myelofibrosis (MF) and is associated with the need for red blood cell transfusion and poor clinical prognosis. JAK inhibitors such as ruxolitinib are used extensively to treat symptoms of MF and improve quality of life and overall survival. However, JAK inhibitors may also contribute to myelosuppression. Therapeutic interventions that allow for optimization of JAK inhibition with no concern of anemia would benefit patients with MF and potentially lower the rate of treatment discontinuation or suboptimal dosing. Recent studies have demonstrated that inhibition of ACVR1/ALK2, a bone morphogenetic protein receptor that is upstream of the transcriptional regulation of hepcidin, could reduce serum hepcidin levels in patients with MF and improve anemia (Verstovsek S et al. Lancet 2023; Oh S et al. Clin Lymphoma Myeloma Leuk 2022). Reducing levels of hepcidin, a key regulator of plasma iron levels, and restoring erythropoiesis would broadly benefit patients with MF. Based on these recent data, we developed zilurgisertib, a potent and selective ALK2 inhibitor that could be administered in combination with ruxolitinib at doses titrated to the needs of patients with MF. Methods and Results: In biochemical and cellular assays, zilurgisertib inhibited ALK2 kinase activity and SMAD1/5 phosphorylation with IC 50 values of 15 nM and 63 nM, respectively. In Huh-7 cells stimulated with BMP-6, zilurgisertib inhibited hepcidin production with an IC 50 of 20 nM, demonstrating the compound is a potent ALK2 inhibitor capable of regulating iron homeostasis via hepcidin. To assess possible off-target effects of zilurgisertib, kinome profiling at 10 μM ATP was performed at Reaction Biology (Malvern, PA) to determine the overall specificity across 356 kinases (see Figure). At 200 nM, zilurgisertib only inhibited ALK2, ALK1 (to 50%), and ALK6 (to 48%). In addition, zilurgisertib at 20 μM did not affect viability of HEK293 cells, a human cell line commonly used to assess general cell health and compound toxicity. Similarly, zilurgisertib did not affect viability of human fibroblasts or endothelial cells at concentrations up to 5 μM. To test whether the combination of ruxolitinib and zilurgisertib could suppress hepcidin and restore erythropoiesis in an in vivo mouse model of cancer-induced anemia, B16F10 cells were injected intraperitoneally, mimicking a metastatic tumor that leads to anemia 1 week after injection. In a dose-dependent manner, zilurgisertib improved hemoglobin by 2 to 3 g/dL and red blood cell counts, while reducing both liver pSMAD and circulating hepcidin levels by 50% or more compared with vehicle control. The combination of zilurgisertib with ruxolitinib had no effect on this activity, suggesting that inhibition of JAK2 does not inhibit erythropoiesis restored following ALK2 inhibition. Conclusion: Taken together, the potent and selective on-target activity of zilurgisertib suggests that ALK2 inhibition could reduce hepcidin and improve anemia, and that the combination of zilurgisertib with ruxolitinib is a rational and attractive approach to mitigate anemia in patients with MF. The combination of ruxolitinib and zilurgisertib is currently being evaluated in a phase 1 clinical trial in patients with anemia due to myeloproliferative disorders (NCT04455841).

Correlation between serum hepcidin level and stages of chronic kidney disease: A cross sectional study

Introduction: Chronic Kidney Disease (CKD) has been associated with significant mortality and morbidity. Despite significant numbers of cases, biomarkers related to iron status and development of anaemia in these patients has not been looked upon extensively. Few biomarkers have been studied, one of which is serum hepcidin levels. We aimed to estimate the serum hepcidin levels in patients with CKD and its correlation with its successive stages. Materials and Methods: The study design was cross-sectional observational study. 51 patients of CKD KDIGO stage II to V were included and patients of obstructive uropathy or malignancy or transplant recipient were excluded from the study. The aim of the study was to evaluate the association between serum hepcidin levels and Stages of CKD in terms of eGFR. Results: The mean serum hepcidin levels which were found in Stage II, III, IV and V of CKD patients was 65.48, 116.03, 136.61 and 160.37 ng/ml respectively. There was a strong negative correlation between eGFR and serum hepcidin level, and this correlation was statistically significant (r = -1.0, p = <0.001). The Krushkal-Wallis Test also provided p value of <0.001 when stages of CKD and serum hepcidin levels were correlated. Conclusion: There was significant positive correlation of serum hepcidin with the stages of CKD (P < 0.001) and the levels of serum hepcidin were found to be significantly higher as the stage increased. Thus, serum hepcidin may be used as a marker of iron metabolism, prognosis and progress of disease in the CKD patients.

Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis.

Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels. PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups. Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD-1.6 (95 % CI:-2.66 to-0.54), p<0.01] and alcoholic liver disease (3 studies) [MD-0.84 (95 % CI:-1.6 to-0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD-0.65 (95 % CI:-1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD-1.02 (CI:-1.59 to-0.45), p<0.01] vs. controls (CI: confidence interval). Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.

Low Serum Hepcidin Levels in Patients with Ulcerative Colitis - Implications for Treatment of Co-existent Iron-Deficiency Anemia.

Ulcerative colitis (UC) is often associated with anemia. Hepcidin, the central regulator of iron homeostasis, is known to be induced by inflammation and suppressed by anemia. It is not clear how hepcidin is affected in those with UC, when both inflammation and anemia may co-exist.Such knowledge may hold implications for treatment. Hematological and iron-related parameters, C-reactive protein (CRP), growth differentiation factor 15 (GDF-15) and erythroferrone (ERFE) (erythroid regulators of hepcidin) levels were estimated in blood from those with UC and in control subjects. Values for hematological and iron-related parameters showed evidence of iron-deficiency and resultant anemia, in patients with UC. The presence of UC was significantly associated with inflammation. Serum levels of ERFE, but not of GDF-15, were significantly higher in patients with UC than in control patients, while hepcidin levels were significantly lower. Serum hepcidin concentrations in patients with UC correlated positively with serum iron, ferritin and GDF-15, and negatively with serum ERFE. The iron status and serum hepcidin levels in UC patients with co-existent anemia were significantly lower and serum ERFE values significantly higher than in those with UC without anemia. The effect of anemia on hepcidin predominated over that of inflammation in patients with UC, resulting in suppressed hepcidin levels. This effect is possibly mediated through erythroferrone. We suggest that a serum hepcidin-guided approach may be useful to guide use of oral iron supplements to treat co-existent iron-deficiency anemia in patients with UC and other chronic inflammatory diseases.

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.

Study of serum hepcidin level and its relation to recombinant human erythropoietin resistence, markers of iron status and C-reactive protein in patients with end stage renal disease on maintenance hemodialysis.

Background: Anemia represents a significant problem to deal with in patients with chronic kidney disease (CKD) on hemodialysis (HD). This work aimed to determine the usefulness of measuring serum hepcidin level in patients with end stage renal disease (ESRD) on maintenance hemodialysis and anemia, and assess the possible correlation between serum hepcidin level and markers of iron status (serum iron, serum ferritin, total iron binding capacity and iron saturation), erythropiotin resistence and inflammatory markers (C-reactive protein). Methods: The study was performed on (50 patients) with end stage renal disease on maintainance hemodialysis. Patients were divided into two groups: group (I): 40 patients who have anemia responsive to erythropoietin therapy and group (II): 10 patients who have anemia resistant to erythropoietin therapy. All patients were subjected to thorough history taking, clinical examination, and laboratory investigations. Results: serum hepcidin level was higher in all patients with erythropoietin resistence index (ERI) 15. There was a highly significant positive correlation between serum hepcidin level and ERI and significant negative correlation between serum hepcidin level and serum iron, ferritin and transferrin saturation. But no significant correlation between serum hepcidin level and C-reactive protein. Conclusion: Hepcidin is associated with anemia, markers of iron status and erythropoietin resistence. If used as a diagnostic tool, it might improve iron therapy in patients with functional iron deficiency due to reticuloendothelial blockage of iron transport. This is important to avoid iron overload and to improve erythropoietin (EPO) response in patients with ESRD.

Clinical significance of serum hepcidin in the diagnosis and treatment of patients with anemia of chronic disease: a meta-analysis

Objective To systematically evaluate the value of serum hepcidin in the diagnosis of Anaemia of Chronic Disease (ACD) in order to provide appropriate treatment. Methods Literature search was performed in PubMed, EMbase, Cochrane Library, CNKI, CBMdisc and CSPD till Jan, 2020. Studies using hepcidin assay for the diagnosis of ACD were included. Two researchers selected the literature according to the pre-defined inclusion and exclusion criteria. Meta-analysis was performed using Stata 15.0. Results A total of 10 studies were included, including 739 patients with 402 ACD patients. Heterogeneity test results suggest that there is no statistical heterogeneity between the included studies and Meta- analysis was performed using a fixed-effects model. Results showed that serum hepcidin levels in patients with ACD combined with SEN, SPE, PLR, NLR, and Diagnostic OR were 0.94 [95% CI (0.90, 0.96)], 0.85 [95% CI (0.81, 0.88)], 6.1 [95% CI (4.8, 7.6)], 0.08 [95% CI (0.05, 0.12)] and 81 [95% CI (47, 139)] respectively. The area under the SROC curve (AUC) value was 0.91. Conclusion Serum hepcidin assay is a valuable method to diagnose ACD in patients. However, due to the limitations of the quantity and quality of the research, the above conclusions need more research to verify.

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.

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.

Iron Deficiency Anemia and Serum Hepcidin Level in Children with Typhoid Fever: A Case–Control Study

Abstract Objective Typhoid fever is a common systemic bacterial infection in children with a complex interplay between serum hepcidin and iron. We investigated the relationship between iron deficiency anemia (IDA) and serum hepcidin level in children with acute typhoid fever. Methods We conducted a preliminary case–control study in Mansoura University Children's Hospital, Egypt from April 2017 to May 2019 including 30 children aged 5 to 15 years with confirmed acute typhoid fever. We recruited 15 healthy nonanemic children, of comparable ages and sex as controls from the same hospital while attending for nonfebrile complaints. Typhoid fever cases were subdivided according to IDA existence into 16 cases with IDA and 14 non-IDA cases. We excluded all children having diseases which may affect serum iron and hepcidin levels, for example, liver, blood, gastrointestinal, and kidney diseases, and patients receiving drugs interfering with iron metabolism. All participants were subjected to complete blood count, serum ferritin, iron, hepcidin levels, and total iron-binding capacity (TIBC). Results In non-IDA typhoid fever group, serum iron level was significantly low, while serum hepcidin level was significantly high when compared with controls (p &lt; 0.001 and p = 0.02, respectively). In IDA typhoid fever group, no statistically significant difference existed as regards serum hepcidin level when compared with controls (p = 0.53). No significant correlations were detected between serum hepcidin levels and hemoglobin, serum iron, ferritin, and TIBC values in each group. Conclusion Preexisting iron status could affect serum hepcidin level in patients with acute typhoid fever. Coexistence of IDA might oppose the up-regulatory effect of acute typhoid fever on serum hepcidin level.

Serum Hepcidin Level in Patients with Acute Lymphoblastic Leukemia (ALL) during The Treatment Phase: Their Effects on Erythropoisis Activity and Iron Reserves

Hepcidin levels increased significantly with increased of iron stores in early phase of acute leukemia patients when erithropoisis pressed by blast cells in bone marrow, then decreased significantly with acute leukemia remission. The study aimed to determine role of hepcidin in activity of erythropoisis and serum iron reserves in acute lymphoblastic leukemia (ALL) patients during phase of therapy. This study used an observational analytic design. Serum hepcidin examination used ELISA methods. Erythropoisis activity was determined by complete blood and reticulocyte percentage. Iron reserves was determined by serum iron and ferritin levels by ECLIA. Result shows a total of 48 patient subjects were divided into groups of induction, consolidation and maintenance phase with an average age of 6.81 years (induction), 9.7 years (consolidation) and 7.8 years (maintenance). In the normality test with Shapiro-Wilk data showed abnormal distribution (p <0.05). Analysis by the Kruskal-Wallis test showed there were differences between the three treatment phases in the examination of hemoglobin, reticulocytes, serum iron, ferritin and hepcidin (p <0.05). In statistical analysis with Spearman's rank correlation shows there is a significant correlation between hemoglobin with ferritin (r = -0.416, p = 0.003), hemoglobin with hepcidin (r = -0.305, p = 0.035), reticulocytes with hepcidin (r = -0.496), p = 0.000) and serum iron with hepcidin (r = -0.302, p = 0.037). We concluded that the higher levels of hepcidin indicate lower levels of hemoglobin, reticulocytes and serum iron in patients with acute lymphoblastic leukemia during treatment phase.

Hepcidin and MELD-XI score as markers of multiple organ failure in patients with heart failure with preserved and reduced ejection fraction

Data on the changes in hepcidin levels in heart failure (HF) patients are contradictory and do not give an answer about its effect on the progression of multiple organ failure. Since the model of end-stage liver disease excluding INR (MELD-XI) reflects the severity of liver and kidney dysfunction, these markers have been suggested to be associated with decompensated HF.Aim. To assess the MELD-XI score and serum hepcidin levels in patients with decompensated HF with different values of left ventricular ejection fraction (EF).Material and methods. The study included 68 patients (29 women, 39 men; mean age 72,3±11,7 years) hospitalized due to decompensated HF. Patients were divided into three groups: reduced (HFrEF) (n=20), mid-range (HFmrEF) (n=23), and preserved EF (HFpEF) (n=24)). Upon admission, along with standard diagnostic tests, all patients were examined for hepcidin-25 levels by enzyme-linked immunosorbent assay. MELD-XI score was calculated. Statistical processing was carried out using the software package Statistica 8.0.Results. Hepcidin levels in the HFrEF group (31,63 ng/ml [22,0; 71,6]) were significantly higher than in the HFmrEF (23,89 ng/ml [21,1; 27,9]) (p&lt;0,05) and HFpEF (26,91 ng/ml [18,6; 31,1]) (p&lt;0,05) groups. In HFpEF, there was a correlation of hepcidin level with body mass index (r=0,47, p&lt;0,05) and chronic obstructive airway diseases (r=0,44, p&lt;0,05). A correlation of hepcidin level with significant cardiac arrhythmias (r=0,61, p&lt;0,05) was revealed in HFmrEF patients. MELD-XI score were significantly increased from 9,44±3,96 for HFpEF and 11,53±3,82 for HFmrEF to 14,3±4,3 for HFrEF (p&lt;0,005). We also revealed correlation of MELD-XI score with hepcidin levels (r=0,3, p&lt;0,05) and EF (r=-0,43, p&lt;0,0003). Patients with a MELD-XI score of &gt;10,4 were more likely to have NYHA class III-IV HF, HFrEF and significantly higher levels of hepcidin (p&lt;0,05 for all) These patients were also more likely to have chronic kidney disease (p&lt;0,05).Conclusion. Hepcidin level and MELD-XI score in patients with decompensated HF are inversely related to left ventricular EF. There is a direct relationship between hepcidin levels and other clinical parameters: body mass index, the presence of chronic obstructive airway diseases and cardiac arrhythmias.

Serum Levels of Hepcidin in Rheumatoid Arthritis and Its Correlation with Disease Activity and Anemia: A Meta-analysis

ABSTRACT Present studies on serum hepcidin levels in patients with rheumatoid arthritis (RA) are inconsistent. We aimed to synthetically evaluate the relationship between hepcidin and RA, and the correlation of serum hepcidin levels and RA disease activity as well as anemia associated with RA. Multiple electronic databases were searched. Pooled standard mean difference (SMD) with 95% confidence interval (CI) and correlation coefficients between hepcidin levels and rheumatoid factor (RF), disease activity for 28 joints (DAS28), and erythrocyte sedimentation rate (ESR) were calculated. Totally, 13 articles were available for this meta-analysis. The results revealed that serum levels of hepcidin were higher in RA patients compared to healthy controls (SMD = 0.573, 95% CI = 0.317 to 0.829, p < .001); RA patients with anemia had higher serum hepcidin levels than RA patients without anemia (SMD = 0.400, 95% CI = 0.080 to 0.720, p = .014); RA patients with pure ACD had higher serum hepcidin levels than RA patients with ACD and IDA (SMD = 0.658, 95% CI = 0.018 to 1.299, p = .044). Moreover, the result of correlation coefficients identified a significant positive correlation between hepcidin levels and RF, DAS28 as well as ESR. Serum hepcidin levels may be closely associated with the development of RA.

Serum markers of iron metabolism in chronic hepatitis C virus infections

Background Hepatitis C virus (HCV) infection is a common cause of chronic hepatitis, which leads to cirrhosis of the liver and hepatocellular carcinoma. Chronic hepatitis can cause iron buildup in the liver and result in liver injury. The major iron metabolism regulator, the hepatic hormone hepcidin, inhibits iron absorption and recycling, and as hepcidin is suppressed by the virus, it contributes to the pathogenesis of the liver. Aim To assess serum iron markers in patients with chronic hepatitis C (CHC) as opposed to people who are healthy and a summary of interactions of HCV and iron overload. Patients and methods This case–control study was performed on 30 hepatitis C-infected Egyptian patients (group I) and 15 apparently healthy control (group II). Routine laboratory investigations, as well as serum hepcidin and iron marker assessments were performed. Results Throughout this study, the serum hepcidin level in patients significantly decreased relative to the control group (P&lt;0.001). The patients showed significantly higher serum iron, transferrin saturation, alanine aminotransferase, and aspartate aminotransferase compared with the control group (P&lt;0.001). Serum albumin in patients’ group was considerably decreased in comparison with the control (P&lt;0.05). There was a highly statistically significant lower platelet count value in patients compared with the control group (P&lt;0.001). The interaction between hepcidin and iron, transferrin, and alanine aminotransferase is significantly negative. Conclusion Hepatic iron deposition is a joint feature in patients with CHC. Chronic HCV infection may reduce serum hepcidin, which may lead to iron overload in these patients. So hepcidin is a surrogate marker for evaluation of iron overload in patients with CHC.

Relationship between Cardiac Geometry and Serum Hepcidin in Chronic Kidney Disease: Analysis from the KNOW-CKD Study.

BackgroundFew studies have examined the relationship between cardiac function and geometry and serum hepcidin levels in patients with chronic kidney disease (CKD). We aimed to identify the relationship between cardiac function and geometry and serum hepcidin levels.MethodsWe reviewed data of 1,897 patients in a large-scale multicenter prospective Korean study. Logistic regression analysis was used to identify the relationship between cardiac function and geometry and serum hepcidin levels.ResultsThe mean relative wall thickness (RWT) and left ventricular mass index (LVMI) were 0.38 and 42.0 g/m2.7, respectively. The mean ejection fraction (EF) and early diastolic mitral inflow to annulus velocity ratio (E/e′) were 64.1% and 9.9, respectively. Although EF and E/e′ were not associated with high serum hepcidin, RWT and LVMI were significantly associated with high serum hepcidin levels in univariate logistic regression analysis. In multivariate logistic regression analysis after adjusting for variables related to anemia, bone mineral metabolism, comorbidities, and inflammation, however, only each 0.1-unit increase in RWT was associated with increased odds of high serum hepcidin (odds ratio, 1.989; 95% confidence interval, 1.358–2.916; P < 0.001). In the subgroup analysis, the independent relationship between RWT and high serum hepcidin level was valid only in women and patients with low transferrin saturation (TSAT).ConclusionAlthough the relationship was not cause-and-effect, increased RWT was independently associated with high serum hepcidin, particularly in women and patients with low TSAT. The relationship between cardiac geometry and serum hepcidin in CKD patients needs to be confirmed in future studies.

The effect of anemia on serum hepcidin levels in patients with heart failure

The effect of anemia on serum hepcidin levels in patients with heart failure

Expression and influencing factors of hepcidin in classical paroxysmal nocturnal hemoglobinuria

目的研究铁调素在经典型阵发性睡眠性血红蛋白尿症（PNH）患者血清中的表达及其影响因素。方法以2016年3月至2017年3月36例经典型PNH患者为研究对象，采用ELISA方法检测血清铁调素水平，并结合患者铁稳态状况和临床资料，分析经典型PNH患者血清铁调素水平与血清铁蛋白（SF）、可溶性转铁蛋白受体、C反应蛋白、EPO、网织红细胞绝对值、网织红细胞血红蛋白等血液学参数的相关性。结果36例经典型PNH患者血清铁调素水平为32.03（23.11，118.48）µg/L，明显低于正常对照组的181.42（106.80，250.53）µg/L（z=−5.107，P<0.001）。其中，铁蛋白正常经典型PNH患者血清铁调素水平为56.41（44.60，95.06）µg/L，经典型PNH伴缺铁组血清铁调素水平为23.75（21.77，30.35）µg/L，均低于正常对照组；而经典型PNH伴铁蛋白升高组血清铁调素水平为336.19（304.19，375.08）µg/L，高于正常对照组、铁蛋白正常经典型PNH组及经典型PNH伴缺铁组。多重线性回归分析显示SF、转铁蛋白饱和度和血清白蛋白水平是经典型PNH患者血清铁调素水平的独立影响因素。结论经典型PNH患者血清铁调素水平减低，其表达主要受铁代谢因素影响。

Serum hepcidin levels and erythropoietin resistance in hemodialysis patients

Introduction Erythropoietin (EPO) resistance is an important cause of anemia in patients with chronic kidney disease. Enhancement of erythropoiesis by EPO requires intact EPO signaling and effective mobilization of iron stores. Enhanced synthesis of hepcidin leads to reduction of iron absorption in the small intestine and sequestering of iron in macrophages. Hepcidin may contribute to EPO resistance through a direct inhibitory effect on erythroid progenitor proliferation and survival. Objective To assess serum hepcidin levels in patients undergoing hemodialysis (HD) treatment and to distinguish its analogous association with anemia parameters and EPO resistance. Patients and methods A cross-sectional study was carried out among HD patients at Nephrology Unit of the Zagazig University Hospital from 2017 to 2018. The study included 90 participants, meeting our inclusion criteria, who had end stage renal disease (ESRD) and were on regular HD three times weekly. All patients were subjected to full history taking and clinical and laboratory assessment. It included routine investigations, with complete blood picture, calcium, phosphorus, parathyroid hormone (PTH), lipid profile, iron panel, and c reactive peptide (CRP). Specific investigations included the EPO resistance index and serum hepcidin measurement. Results Hepcidin is positively related to EPO resistance index. EPO resistance index as well as ferritin were significant determinants of hepcidin in HD patients. Conclusion Hepcidin is associated with anemia, iron status, and microinflammation in HD patients. If used as a diagnostic tool, it might improve iron therapy during periods of reticuloendothelial blockage of iron transport. This is important to avoid iron overload and to improve EPO response in patients with ESRD.

Serum Hepcidin Detects Iron Deficiency Anemia in HIV Infected Patients with Anemia of Inflammation

INTRODUCTION: The etiology of HIV- associated anemia is multifactorial. We previously found a high prevalence of anaemia of inflammation and anemia due to micronutrient deficiencies in HIV patients (Eur J Pediatr 2012, 17:531). Inflammatory disease confounds the value of standard diagnostic markers, posing a challenge to the detection of iron deficient and iron-restricted erythropoiesis. Using serum hepcidin as a biomarker, we tested the hypothesis that total body iron stores like inflammatory signals would also influence serum hepcidin levels in patients with HIV infection.METHODS: Healthy subjects, patients with pure iron deficiency anemia (IDA) andpatients with HIV infection were prospectively enrolled after obtaining informed consent. Using sex adjusted WHO values for anemia diagnosis, ferritin <12µg/L, and CRP values, subjects were categorized into healthy and IDA groups (N Engl J Med 2015, 373:485). Using age adjusted WHO values for anemia, patients with HIV were divided into anemic and non-anemic groups. Using the soluble transferrin receptor (sTfR)/log ferritin (F) index, we defined those subjects with an sTfR-F index < 1.03 as having anemia of inflammation (AI) and those subjects with an sTfR-F index ≥1.03 as having IDA superimposed on AI (Am J Hematol. 2011, 86:923). All laboratory analytes were measured using standard commercial assays.RESULTS: The demographic characteristics of the different groups in the study population are shown in table 1. Compared with healthy controls, mean hemoglobin was significantly lower in patients with pure IDA, HIV patients with anemia, and HIV patients without anemia (p<0.001). The serum soluble transferin receptor (sTfR) levels and serum erythropoietin levels were significantly elevated in pure IDA patients (p<0.001) and HIV patients with anemia (p<0.001) compared with healthy controls, reflecting erythropoietic stress. Compared with healthy controls, serum hepcidin levels were markedly lower in pure IDA patients (p<0.01) and HIV patients with anemia suggesting that iron status influenced hepcidin levels more profoundly than inflammation in HIV infected patients. We also measured erythrocyte ZPP levels and found them to be significantly higher in pure IDA patients (p<0.001) and HIV patients with anemia (p<0.001) compared to healthy controls. All HIV patients with anemia had an sTfR-F index ≥1.03 suggesting the presence of IDA superimposed on AI. Interestingly, serum hepcidin levels correlated inversely with the sTfR-F index in both patients with pure IDA (ρ=-0.76; p<0.001) and in HIV patients with anemia (ρ=-0.4; p<0.02). Similarly, ZPP levels correlated linearly with the sTfR-F index in pure IDA patients (ρ=0.6; p<0.002) and in HIV patients with anemia (ρ=0.5; p<0.001).CONCLUSION: Our data shows significant differences in serum hepcidin and erythrocyte ZPP levels in healthy, IDA and HIV patients. These two biomarkers could be included in the panel of diagnostic tests used to detect iron deficiency anemia superimposed on anemia of inflammation. Further studies are needed to provide the appropriate cut-off values with which IDA can be detected with appropriate sensitivity and specificity in patients with anemia of inflammation. Such data may also be helpful in monitoring therapeutic responses to iron.Table 1Haematological and biochemical parametersHealthy(n = 45)Pure IDA(n=33)HIV with anemia(n=46)HIV without anemia(n=46)Age ± SD31±7.525±3.635±11.939±12Hemoglobin ± SD(g/dl)15.2±1.210.1±1.3a,c,d11±1.1a,d13.8±1.3aMCV ± SD85±4.274±7.780±8.785±4.6Biochemical parametersSerum Ferritin*(ng/mL)57 (43, 83)4.5a,c,d (3.1, 7)14a,d (7, 34)47 (32, 130)Serum sTfR*(mg/L)1.7b,c (1.3, 2)4.3 (3, 6.3)2.5 (2, 3.7)1.8b,c (1.3, 2.1)Serum Erythropoietin*(mU/mL)6.5b,c (4.9, 9.8)40 (28, 61)20b (13, 32)10b,c (5, 14)BiomarkersSerum Hepcidin*(ng/mL)20.6 (14.2, 25.6)0.5a (0.1, 3.3)11.6b (2.9, 29.8)Erythrocyte ZPP*(μmol/mol heme)50b,c (40, 58)200 (117, 247)101b (69, 131)56b,c (42, 75)*All non Gaussian distributed data are presented as median (25th percentile, 75th percentile); ap < 0.05 compared with healthy subjects, bp < 0.05 compared with pure IDA patients, cp < 0.05 compared with HIV anemia patients, dp < 0.05 compared with HIV without anemia patients. DisclosuresNo relevant conflicts of interest to declare.

Assessment of serum hepcidin levels in patients with non-ST elevation myocardial infarction

OBJECTIVE Hepcidin is an acute-phase reactant produced in the liver displaying intrinsic antimicrobial activity. There are few studies about hepcidin considered to be acute and chronic inflammatory marker in acute coronary syndromes patients. We investigated in our study whether the level of hepcidin has increased in the acute phase of non-ST elevation myocardial infarction patients (NSTEMI) known as acute inflammatory aggravation of chronic atherosclerotic process. METHODS Seventy patients with NSTEMI and twenty healthy people were recruited as controls in this observational cross-sectional study. Serum hepcidin levels were determined by ELISA, and troponin levels were measured by standard laboratory methods. Levels of hepcidin and troponin were measured at admission and 6 hours later. Mean values of continuous variables were compared between groups using the Student t-test or Mann-Whitney U test, according to whether normally distributed or not, as tested by the Kolmogorov-Smirnov test. Serum troponin and hepcidin levels measured at admission and after 6th hours were compared using paired t-test. RESULTS Hepcidin level was similar between NSTEMI and controls at admission (24.55±32.13, 23.67±33.62 ng/mL, p>0.05, respectively). Also, serum hepcidin levels did not change significantly from baseline in blood samples taken after 6 hour from admission in NSTEMI patients (24.55±32.13 ng/mL, 29.75±31.48 ng/mL, p=0.62, respectively). However, serum troponin levels were increased significantly compared to baseline (0.29±3.56, 2.92±7.2 ng/mL, p<0.01). CONCLUSION Our findings suggest that hepcidin could not be use as a marker of myocardial necrosis in acute phase such as troponin in patients with NSTEMI.