Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia

The aim of the present study is to evaluate in an elderly hospitalized population the diagnostic value of the serum transferrin receptor (sTfR) in distinguishing IDA (iron deficiency anemia) from ACD (anemia of chronic disease) as compared to conventional laboratory tests of iron metabolism, especially serum ferritin. In a prospective study, 34 patients with IDA and 38 patients with ACD (a chronic disorder in 23 and an acute infection in 15) were evaluated using iron status tests including serum transferrin receptor assay. The iron stores were assessed by bone marrow examination. sTfR levels were elevated (>28.1 nmol/L) in 68% of the IDA patients but also in 43% of the patients with ACD-chronic inflammation and 33% with ACD-acute infection. Serum ferritin was the best test to differentiate IDA from ACD patients. We conclude that serum ferritin is a more sensitive and specific parameter than the sTfR assay to predict the bone marrow iron status in an elderly anemic population.     

Mass spectrometry evaluation of the hepcidin‐25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients

In this study, mass spectrometry was used to evaluate the hepcidin‐25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients using the absence of stainable bone marrow iron as the gold standard criterion for iron deficiency (ID). In addition, correlation coefficients for hepcidin‐25 vs. haematimetric and biochemical iron parameters, and C‐reactive protein (CRP) were determined. The optimal cut‐off for hepcidin‐25 was 31.5 ng/mL corresponding to a sensitivity and specificity of 82% and 95%, respectively, for ID. For ferritin, a sensitivity and specificity of 70% and 100%, respectively, correspond to an optimal cut‐off of 41.5 μg/L. Receiver operating characteristics curve analysis revealed that mass spectrometry analysis of hepcidin‐25 does not appear to be superior to ferritin in the diagnosis of ID in elderly anaemic patients with concurrent inflammation. Hepcidin‐25 shows a strong positive correlation with ferritin, and also correlates positively with CRP, in this patient population.     

Serumhepcidin bei Eisenmangelanämie und Anämie chronischer Erkrankungen im geriatrischen Kollektiv

Background

Iron deficiency anemia (IDA) and anemia of chronic diseases (ACD) are common in the geriatric population. However, differentiation between IDA and ACD is still problematic. Hepcidin is a key regulator of iron homeostasis: downregulation in the presence of iron deficiency allows enteral iron resorption, while upregulation in case of chronic inflammation blocks it. We aimed at studying whether serum hepcidin levels might serve as diagnostic parameter to differentiate between IDA and ACD among elderly.

Patients and methods

A total of 37 patients (age 69–97 years) were divided into 4 groups: group I (IDA), group II (ACD), group III (controls), and group IV (IDA/ACD). Serum hepcidin levels were analyzed using a commercially available ELISA kit (DRG Instruments, Marburg, Germany). Differences in hepcidin levels were tested with nonparametric methods.

Results

We could show a strong positive correlation between serum hepcidin and ferritin (Spearman rho 0.747) and a statistic significant difference of hepcidin levels among all groups (p?=?0.034). Hepcidin levels between ACD and controls differed significantly (p?=?0.003).

Conclusion

Despite the small number of patients included in this study, which reduces the strength of the study’s evidence, results conform with the current literature: it can be assumed that hepcidin will be used as a diagnostic parameter to differentiate between IDA and ACD in the future. However, more studies with larger patient groups are urgently needed to answer this question.     

铁代谢指标测定对慢性病贫血并发缺铁的诊断意义

目的 :了解血清铁蛋白 (SF)、转铁蛋白饱和度 (TS)、血清转铁蛋白受体 (sTFR)及sTFR/log(SF)等外周血铁代谢指标对缺铁性贫血 (IDA)、慢性病贫血 (ACD)和慢性病贫血并发缺铁 (ACD/ID)的鉴别诊断意义。方法 :病例为IDA患者 18例 ,ACD患者 2 0例 ,其中 10例为ACD/ID患者。SF测定采用微粒酶免疫法 ,TS测定采用化学发光法 ,sTFR测定采用双夹心抗体酶联免疫吸附法。结果 :IDA患者的SF值、TS值显著低于ACD患者 ,其sTFR、sTFR/log(SF)值显著高于ACD患者。ACD患者中 ,ACD/ID患者与无缺铁的ACD(ACD/IR)患者间SF值无显著差别 ;但ACD/ID患者的TS值明显低于ACD/IR患者 ,而sTFR和sTFR/log(SF)值则显著高于ACD/IR患者。TS<4 0 %对ACD/ID检出的敏感性为 10 0 % ,特异性为 6 7% ;sTFR >30nmol/L对ACD/ID检出的敏感性为 90 % ,特异性为 82 % ;sTFR/log(SF) >2 0对ACD/ID检出的敏感性和特异性均为 90 %。结论 :新的铁代谢指标sTFR ,尤其是sTFR/log(SF)是传统铁代谢指标的必要补充 ,联合应用上述铁代谢指标可对ACD、IDA和ACD/ID患者进行准确的鉴别诊断。     

Growth differentiation factor 15 in anaemia of chronic disease,iron deficiency anaemia and mixed type anaemia

Recently, the iron and erythropoiesis‐controlled growth differentiation factor 15 (GDF15) has been shown to inhibit the expression of hepcidin in β‐thalassaemia patients, thereby increasing iron absorption despite iron overload. To access the diagnostic and pathogenic impact of GDF15 in inflammatory anaemia the association of GDF15 expression with serum iron parameters and hepcidin was studied in patients suffering from iron deficiency anaemia (IDA), anaemia of chronic disease (ACD) and ACD subjects with true iron deficiency (ACD/IDA). GDF15 was significantly increased in both ACD and ACD/IDA, but not in IDA subjects as compared to controls. In contrast, hepcidin levels were significantly lower in IDA and ACD/IDA subjects than in ACD patients . IDA and ACD/IDA, but not ACD, showed an association between GDF15 and soluble transferrin receptor, an indicator of iron requirement for erythropoiesis. However, GDF15 did not correlate to hepcidin in either patient group. While GDF15 levels were linked to the needs for erythropoiesis and iron homeostasis in IDA, the immunity‐driven increase of GDF15 may not primarily affect iron homeostasis and hepcidin expression. This indicates that other ACD‐related factors may overcome the regulatory effects of GDF15 on hepcidin expression during inflammation.     

Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access® sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.     

Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease

Anemia of chronic disease (ACD) is frequently found in patients with chronic immune activation. Since most studies on ACD pathophysiology were performed with cell culture or animal models but not in humans, we examined 37 ACD patients suffering from autoimmune diseases or infections, 10 subjects with iron-deficiency anemia (IDA), 10 anemic patients with hereditary spherocytosis (HS), and 27 age-matched controls. Although hemoglobin concentrations were comparable between ACD and IDA patients, the latter presented with significantly higher serum erythropoietin concentrations than ACD patients. The significant negative correlation between erythropoietin and hemoglobin levels observed in IDA patients was also found in a group of anemic but not hypoferremic hereditary spherocytosis subjects, but not in ACD patients. Increased serum concentrations of the hepcidin precursor prohepcidin were paralleled by a decreased expression of the iron exporter ferroportin in circulating monocytes of ACD patients. In the latter cells, increased amounts of the iron storage protein ferritin and a reduced activity of iron-regulatory protein indicated monocyte iron accumulation. Our data indicate that hypoferremia in ACD may result from downregulation of ferroportin expression by hepcidin and cytokines with subsequent iron retention in monocytes. Together with a diminished erythropoietin formation, the impaired iron recirculation from monocytes may be central in the pathophysiology of ACD in humans.     

Serum hepcidin in clinical specimens

The hepatic antimicrobial protein, hepcidin, is implicated in duodenal iron absorption and mobilization. Overexpression of the hepcidin gene is associated with a hypoferraemic, microcytic, iron-refractory anaemia. On the basis of these observations, it has been proposed that hepcidin is a mediator of the common clinical syndrome, anaemia of chronic disease (ACD), and recent findings evaluating urinary hepcidin production in patients support this hypothesis. In the present report, serum hepcidin concentrations were measured in 55 specimens submitted for ferritin determination, and in 37 specimens collected from anaemic patients undergoing diagnostic bone marrow examination. The serum hepcidin concentration exhibited a statistically significant correlation with serum ferritin concentrations in both patient subsets. No statistically significant correlations were observed between serum hepcidin and other laboratory markers of iron status or anaemia diagnosis. Serum hepcidin does not appear to correlate as well with clinical diagnosis as urinary hepcidin, suggesting that a better understanding of the clearance and metabolism of this protein is required to understand fully its potential contribution to the pathogenesis of ACD.     

High serum transferrin receptor level in anemia of chronic disorders indicates coexistent iron deficiency

Blood transferrin receptor (TR) level is largely determined by the quantum of erythropoiesis and by intracellular iron content of the cells of the erythroid lineage. Hence, a high serum TR level has been found to be useful in distinguishing iron deficiency anemia (IDA) from anemia of chronic disorders (ACD). In order to examine its potential role in the diagnosis of concomitant iron deficiency in ACD, we determined serum TR levels in 130 cases of ACD, in 25 cases of IDA, and in 40 normal adults. As expected, all patients of IDA had significantly higher serum TR levels compared to the normal subjects (4.2-19.2 microg/dL vs. 1.3-3.0 microg/dL) (P < 0.002). In 11/25 cases of IDA, the total iron-binding capacity (TIBC) was in the normal range although bone marrow iron store was absent and serum TR levels were high, thereby highlighting the superiority of TR level in the diagnosis of iron deficiency compared to TIBC. Although 54% (70/130) patients of ACD had normal or low serum TR levels (0.9-3.0 microg/dL) as expected, in 46% (60/130) of ACD patients, serum TR levels were high (3.2-11.0 microg/dL). Mean corpuscular volume, red cell distribution width, and transferrin saturation were significantly lower (P < 0.001) in the latter group of patients compared to the former, and these parameters resembled those in IDA patients. Also, serum iron was lower and TIBC was higher in this group of ACD patients compared to those with normal or low serum TR. All these features point to an "IDA-like" profile of ACD patients with high TR and support the possibility of co-existent iron deficiency in this subgroup of ACD patients. In light of these observations it would be prudent to treat ACD patients with high serum TR levels with iron replacement therapy.     

Association between baseline serum hepcidin levels and infection in kidney transplant recipients: Potential role for iron overload

Background

The liver‐synthesized peptide hepcidin is a key regulator of iron metabolism and correlates with total iron stores. We analyzed the association between pre‐transplant hepcidin‐25 levels and infection after kidney transplantation (KT).

Methods

Serum hepcidin‐25 levels were measured at baseline by high‐sensitivity ELISA in 91 patients undergoing KT at our institution between December 2011 and March 2013. The impact of this biomarker on the incidence of post‐transplant infection (excluding lower urinary tract infection) during the first year was assessed by Cox regression.

Results

Mean hepcidin‐25 level was 82.3 ± 67.4 ng/mL and strongly correlated with serum ferritin (Spearman's rho = 0.703; P < .001). There were no significant differences in hepcidin‐25 levels between patients with or without overall infection (96.4 ± 67.5 vs 72.6 ± 66.7 ng/mL; P = .101). Such difference was evident for opportunistic (128.9 ± 75.0 vs 73.0 ± 62.3 ng/mL; P = .003) and, to a lesser extent, surgical‐site infection (107.5 ± 73.3 vs 76.5 ± 65.2 ng/mL; P = .087). Patients with hepcidin‐25 levels ≥72.5 ng/mL had higher 12‐month cumulative incidence of overall infection (51.2% vs 29.2%; P = .032). After multivariate adjustment, hepcidin‐25 ≥72.5 ng/mL acted as an independent risk factor for overall (adjusted hazard ratio [aHR] 3.86; 95% confidence interval [CI] 1.49‐9.96; P = .005) and opportunistic infection (aHR 4.32; 95% CI 1.18‐15.75; P = .027).

Conclusion

Elevated baseline serum hepcidin‐25 levels were associated with increased risk of infection after KT, suggesting a role for iron overload in the individual susceptibility to post‐transplant infection.     

Iron deficiency anemia in older adults: A review

Anemia in older adults is a risk factor for numerous negative outcomes. There is no standard definition, but in most studies, anemia is defined as a hemoglobin value <12 g/dL for women and <13 g/dL for men. Absolute iron deficiency anemia is defined as the combination of anemia and the absence of total body iron. Serum ferritin is the most frequently used diagnostic parameter, but its concentration increases with age and in the presence of inflammatory diseases. Other laboratory tests, such as transferrin saturation, soluble transferrin receptor and the soluble transferrin receptor/ferritin index might provide useful information, but there is a wide variety in the cut‐off values and interpretation of the results. Recent research regarding hepcidin as a central regulator of iron homeostasis is promising, but it has not been used yet for the routine diagnosis of iron deficiency anemia. In older iron deficiency anemia patients, an esophagogastroduodenoscopy and colonoscopy should be initiated in order to identify the underlying bleeding cause. CT colonography can replace a colonoscopy, and in specific cases, a video capsule is recommended. It remains crucial to keep in mind which potential benefits might be expected from these investigations in this vulnerable population, taking into account the comorbidity and life expectancy, and one should discuss in advance the possible therapeutic options and complications with the patient, a family member or a proxy. Oral iron administration is the standard treatment, but parenteral iron is a convenient and safe way to provide the total iron dose in one or a few sessions. Geriatr Gerontol Int 2018; 18: 373–379 .     

Hepcidin/Ferritin Ratios Differ Among Non‐Dialyzed Chronic Kidney Disease Patients,and Patients on Hemodialysis and Peritoneal Dialysis

The serum levels of hepcidin generally increase in patients with chronic kidney disease (CKD) due to inflammation or a decline in the glomerular filtration rate. However, the differences in the ferrokinetics among dialysis modalities are unclear. We investigated the relationship between serum levels of hepcidin and ferritin among non‐dialyzed CKD (ND), hemodialysis (HD), and peritoneal dialysis (PD) patients. We recruited 285 CKD patients (117 ND, 80 HD, and 88 PD patients) and measured the serum levels of hepcidin‐25, ferritin, hemoglobin, iron, transferrin saturation (TSAT), albumin, and high sensitivity C‐reactive protein (hs‐CRP). Hepcidin‐25 levels were elevated in all CKD patients and were significantly higher in PD than in ND and HD patients. The hepcidin/ferritin ratio was significantly higher in PD patients independent of TSAT, hemoglobin, hs‐CRP, and serum albumin. Hepcidin/ferritin ratio, associated with both dialysis modality and inflammation, is expected to be a useful indicator of anemia in CKD.     

Can Serum Gdf-15 be Associated with Functional Iron Deficiency in Hemodialysis Patients?

Functional iron deficiency (FID) incidence is gradually increasing in hemodialysis (HD) patients. Recently, high levels of GDF-15 supressed the iron regulatory protein hepcidin and GDF-15 expression increased in iron-deficient patients. The relationship between FID, GDF-15, and hepcidin is currently unknown. The present study aimed to evaluate the association between GDF-15, hepcidin, and FID in chronic HD patients. Serum GDF-15 and hepcidin concentrations were measured in 105 HD patients and 40 controls. FID is defined as serum ferritin >800 ng/mL, TSAT <25 %, Hb levels <11 g/dL, and reticulocyte haemoglobin content (CHr) <29 pg. Serum GDF-15 and hepcidin levels were increased significantly in HD patients with FID, compared to HD patients without anemia and controls. GDF-15 correlated with ferritin, hepcidin, and CRP in the entire cohort. GDF-15 was related to ferritin and CRP in HD patients with FID. GDF-15 is better diagnostic marker than hepcidin for detection of FID [AUC = 0.982 (0.013) versus AUC = 0.921 (0.027); P = 0.0324]. GDF-15 appears to be a promising tool for detection of FID. High levels of ferritin and CRP correlated with GDF-15. Our results support GDF-15 as a new mediator of FID via hepcidin, chronic inflammation, or unknown pathways.     

Association of Hepcidin With Anemia Parameters in Incident Dialysis Patients: Differences Between Dialysis Modalities

Hepcidin's relationships with other variables are unclear. We evaluated associations of serum hepcidin with clinical parameters in ESRD patients. Ninety‐nine incident dialysis patients, including 57 on peritoneal dialysis (PD) and 42 on HD, were prospectively followed for 6 months. Serum hepcidin levels significantly increased during initial 6 months of dialysis. In the multivariate regression model, independent predictors of serum hepcidin levels in ESRD patients before maintenance dialysis were interleukin‐6, ferritin, phosphate, iron, and aspartate transaminase. Six months after initiating dialysis, serum hepcidin levels were independently predicted by ferritin, total iron binding capacity (TIBC), and aspartate transaminase in all patients, whereas by ferritin and TIBC in PD patients, and ferritin, TIBC, and 24‐h urine volume in HD patients. Serum hepcidin levels are differentially associated with anemia parameters in PD compared with HD patients. Urine volume was an independent predictor of hepcidin levels in early HD patients.     

Single values of serum transferrin receptor and transferrin receptor ferritin index can be used to detect true and functional iron deficiency in rheumatoid arthritis patients with anemia

OBJECTIVE: To elucidate the use of serum transferrin receptor (sTfR) to distinguish between iron-deficiency anemia (IDA) and anemia of chronic disease (ACD), and to establish an improved scheme to identify functional iron deficiency (FID) in rheumatoid arthritis (RA) patients with anemia. METHODS: We studied 30 anemic RA patients whose iron status was confirmed by bone marrow examination and determination of the sTfR level, serum ferritin level, and sTfR-log ferritin index (TfR-F Index). All patients with diminished or exhausted iron stores (n = 18) received oral iron supplementation. RESULTS: Baseline values of sTfR and the TfR-F Index predicted the response correctly in all patients who received supplementation treatment and were normal in 10 of 11 patients with normal initial iron stores (ACD). CONCLUSION: The results of this study elucidate the roles of sTfR and the TfR-F Index in the differential diagnosis between IDA and ACD and provide direct evidence that these parameters are useful in detecting FID, irrespective of the concurrent iron storage status.     

Bone marrow iron distribution,hepcidin, and ferroportin expression in renal anemia

Abstract

Objectives

The hepcidin–ferroportin system is involved in both conditions associated with iron-restricted erythropoiesis in renal anemia: iron deficiency and anemia of chronic disorders. As serum hepcidin could aid diagnosis, we investigated its relationships with bone marrow iron distribution, hepcidin–ferroportin expression in bone marrow cells, and peripheral iron indices in non-dialysis chronic kidney disease (CKD) patients.

Methods

Fifty-four epoetin and iron naive CKD patients entered this prospective, observational study. According to bone marrow iron distribution (iliac crest biopsy, Perls' stain), 26 had iron deficiency anemia, 21 anemia of chronic disorders and 7 had normal iron stores. Medullar hepcidin and ferroportin expression (immunofluorescence (IF), semiquantitative scales) and serum hepcidin (Hep25 – ELISA) were the main studied parameters.

Results

Low hepcidin and high ferroportin expression by erythroblast and macrophage were seen in iron deficiency anemia, while the opposites were true in anemia of chronic disorders. In regression analysis, higher Hep25 and ferritin predicted hepcidin expression (R²=0.48; P < 0.0001), while lower ferritin and Hep25 - predicted ferroportin expression (R² = 0.29; P = 0.003) by erythroblast; inflammation had no contribution. In ROC analysis, serum hepcidin and ferritin had similar moderate utility in differentiating iron deficiency anemia from anemia of chronic disorders (AUC 0.63 95% CI 0.47–0.79 and 0.76 95% CI 0.61–0.90, respectively).

Conclusions

Thus, in anemic epoetin naive non-dialysis CKD patients, hepcidin and ferroportin expression by erythroblast and macrophage are closely related to bone marrow iron distribution. Although the hepcidin–ferroportin system seems regulated by ferritin-driven Hep25, serum hepcidin and peripheral iron indices are of little help in describing bone marrow iron status.     

Comparison of 2‐Week Versus 4‐Week Dosing Intervals of Epoetin Beta Pegol on Erythropoiesis and Iron Metabolism in Hemodialysis Patients

Epoetin beta pegol (a continuous erythropoietin receptor activator; CERA) is usually administered once in 4 weeks or once monthly. However, the optimal dosing interval remains unknown. We, therefore, compared the effect of CERA administration between dosing intervals of 2 weeks (TWICE group) and 4 weeks (ONCE group) on erythropoiesis and iron metabolism in 20 hemodialysis patients. CERA was administered intravenously at weeks 0 and 2 for the TWICE group, and at week 0 for the ONCE group. Levels of hemoglobin (Hb), reticulocyte count, ferritin, transferrin saturation, content of Hb in reticulocytes and hepcidin‐25 were monitored weekly for 4 weeks. Hemoglobin levels were significantly increased at weeks 3 and 4 in the TWICE group, while a gradual decrease after a significant increase at week 1 was observed in the ONCE group. Ferritin levels remained significantly low from week 1 to week 4 in the TWICE group. On the other hand, ferritin levels increased beyond baseline levels at week 4 in the ONCE group. Although hepcidin‐25 did not significantly increase in the TWICE group, significant increases beyond baseline levels at weeks 3 and 4 were found in the ONCE group. These results indicate that continuous erythropoiesis was achieved with biweekly administration of CERA. Moreover, CERA at a 2‐week interval led to a sustained suppression of ferritin and hepcidin‐25 levels, suggesting a favorable influence on iron metabolism.     

Serum hepcidin as a diagnostic test of iron deficiency in premenopausal female blood donors

Background

Currently used indicators of iron status have limitations. Hepcidin, a key regulator of iron metabolism, is reduced in iron deficiency. We sought to determine the properties of hepcidin as a diagnostic test of iron deficiency.

Design and Methods

Sera from female, non-anemic, whole blood donors were analyzed for hepcidin (enzyme-linked immunosorbent assay), ferritin, soluble transferrin receptor and C-reactive protein. Iron deficiency was defined as (i) serum ferritin less than 15 ng/mL or (ii) soluble transferrin receptor /log(ferritin) index greater than 3.2 if the C-reactive protein concentration was less than 10 mg/L, or greater than 2.2 if the C-reactive protein concentration was greater than 10 mg/L). Receiver operating characteristic curves were plotted to determine the overall utility and identify optimal cut-points of hepcidin as a test of iron deficiency.

Results

In 261 blood donors the prevalence of iron deficiency defined by ferritin concentration was 59/261 [22.6% (17.5, 27.7)], whereas defined by soluble transferrin receptor/log(ferritin) index it was 53/261 [20.4% (15.4, 25.2)]. The 95% reference range of hepcidin concentration in the iron-replete population was 8.2–199.7 ng/mL. The area under the receiver operating characteristic curve for hepcidin compared with ferritin concentration less than 15 ng/mL was 0.87 (0.82, 0.92), while that compared with the soluble transferrin receptor /log(ferritin) index was 0.89 (95% CI 0.84, 0.93). For a diagnosis of iron deficiency defined by the soluble transferrin receptor/log(ferritin) index, hepcidin less than 8 ng/mL had a sensitivity of 41.5% and a specificity of 97.6%, while hepcidin less than 18 ng/mL had a sensitivity of 79.2% and a specificity of 85.6%.

Conclusions

Serum hepcidin concentration may be a useful indicator of deficient iron stores. Further studies are required to evaluate the role of hepcidin in the diagnosis of iron deficiency in other groups of patients.     

Impaired regulation of serum hepcidin during phlebotomy in patients with chronic hepatitis C

Aim: This study was conducted to determine the clinical relevance of hepcidin, a recently identified key iron regulatory hormone, in patients with chronic hepatitis C virus (C‐HCV). Methods: Serum hepcidin levels were measured in 9 C‐HCV patients by surface‐enhanced laser desorption/ionization time of flight mass spectrometry (SELDI‐TOF‐MS), and compared to those of healthy controls. Sequential changes of hepcidin were also investigated during phlebotomy. Results: Serum hepcidin and ferritin were significantly higher in C‐HCV than in controls (P = 0.0002), these two variables were strongly related to each other (r = 0.658; P < 0.01), and phlebotomy significantly decreased serum hepcidin in C‐HCV (P = 0.0007); all these results recollect the hepcidin response to iron signal. Hepcidin/ferritin ratio, an index of the appropriateness of hepcidin expression relative to iron overload, was significantly lower in C‐HCV than in controls (0.33 ± 0.41 vs. 0.73 ± 0.36, P = 0.0068). This relative impairment of hepcidin expression was not reversible after phlebotomy (P = NS). Conclusions: Although the hepcidin expression responds to iron conditions in C‐HCV, this response is relatively limited. This relative impairment of hepcidin expression may be relevant to disease progression, and thus correction of its regulation may be beneficial for these iron‐overloaded C‐HCV patients.     

Serum hepcidin levels are innately low in HFE-related haemochromatosis but differ between C282Y-homozygotes with elevated and normal ferritin levels

HFE C282Y-homozygosity has been associated with low hepcidin expression, leading to increased ferritin levels. However, serum hepcidin protein levels have not been documented in humans. In the current study, we compared serum hepcidin levels of newly diagnosed HFE C282Y-homozygotes with ( N  = 15) and without ( N  = 7) elevated serum ferritin levels to levels of 40 controls (20 heterozygotes and 20 wild types). In addition, hepcidin levels of four C282Y homozygotes were investigated during the course of all phlebotomy treatment phases. Serum hepcidin levels were lower in HFE C282Y-homozygotes (median; 25th–75th percentile: 1·88; 0·78–2·77 nmol/l) compared to controls (2·74; 1·45–5·39). Hepcidin/ferritin ratios were also lower in homozygotes. Homozygotes with an elevated serum ferritin had a higher serum hepcidin but a lower hepcidin/ferritin ratio than those with normal ferritin (2·28; 1·62–3·23 nmol/l hepcidin vs. 0·80; 0·60–1·29 and 3·63; 2·72–7·59 pmol hepcidin/μg ferritin vs. 13·2; 5·15–14·2). Serum hepcidin decreased during the depletion phase of phlebotomy and remained low during maintenance. This study showed that serum hepcidin is innately low in HFE -related haemochromatosis. Elevated ferritin levels were associated with increased hepcidin levels while erythropoiesis lead to lower hepcidin levels. During depletion, therefore, hepcidin levels are decreased, which may exacerbate intestinal iron absorption.