HFE hemochromatosis: an overview about therapeutic recommendations

Abstract Hemochromatosis is currently characterized by the iron overload caused by hepcidin deficiency. Large advances in the knowledge on the hemochromatosis pathophysiology have occurred due to a better understanding of the protein of the iron metabolism, the genetic basis of hemochromatosis and of other iron overload diseases or conditions which can lead to this phenotype. In the present review, the main aims are to show updates on hemochromatosis and to report a practical set of therapeutic recommendations for the human factors engineering protein (HFE) hemochromatosis for the p.Cys282Tyr (C282Y/C282Y) homozygous genotype, elaborated by the Haemochromatosis International Taskforce.

Effect of active component compound of Epimedii Folium,Astragali Radix,and Puerariae Lobatae Radix on expression of ADAM17 in HT22 cells by mediating hepcidin / 中国中药杂志

Alzheimer's disease(AD) patients in China have been surging, and the resultant medical burden and care demand have a huge impact on the development of individuals, families, and the society. The active component compound of Epimedii Folium, Astragali Radix, and Puerariae Lobatae Radix(YHG) can regulate the expression of iron metabolism-related proteins to inhibit brain iron overload and relieve hypofunction of central nervous system in AD patients. Hepcidin is an important target regulating iron metabolism. This study investigated the effect of YHG on the expression of a disintegrin and metalloprotease-17(ADAM17), a key enzyme in the hydrolysis of β amyloid precursor protein(APP) in HT22 cells, by mediating hepcidin. To be specific, HT22 cells were cultured in vitro, followed by liposome-mediated siRNA transfection to silence the expression of hepcidin. Real-time PCR and Western blot were performed to examine the silencing result and the effect of YHG on hepcidin in AD cell model. HT22 cells were randomized into 7 groups: control group, Aβ25-35 induction(Aβ) group, hepcidin-siRNA(siRNA) group, Aβ25-35 + hepcidin-siRNA(Aβ + siRNA) group, Aβ25-35+YHG(Aβ+YHG) group, hepcidin-siRNA+YHG(siRNA+YHG) group, Aβ25-35+hepcidin-siRNA+YHG(Aβ+siRNA+YHG) group. The expression of ADAM17 mRNA in cells was detected by real-time PCR, and the expression of ADAM17 protein by immunofluorescence and Western blot. Immunofluorescence showed that the ADAM17 protein expression was lower in the Aβ group, siRNA group, and Aβ+siRNA group than in the control group(P<0.05) and the expression was lower in the Aβ+siRNA group(P<0.05) and higher in the Aβ+YHG group(P<0.05) than in the Aβ group. Moreover, the ADAM17 protein expression was lower in the Aβ+siRNA group(P<0.05) and higher in the siRNA+YHG group(P< 0.05) than in the siRNA group. The expression was higher in the Aβ+siRNA+YHG group than in the Aβ+siRNA group(P<0.05). The results of Western blot and real-time PCR were consistent with those of immunofluorescence. The experiment showed that YHG induced hepcidin to up-regulate the expression of ADAM17 in AD cell model and promote the activation of non-starch metabolic pathways, which might be the internal mechanism of YHG in preventing and treating AD.

Hepcidin and Erythroferrone Levels in Child-Bearing Women with Iron Deficiency Anemia / 中国实验血液学杂志

OBJECTIVE@#To detect serum hepcidin and erythroferrone levels in child-bearing women with iron deficiency anemia (IDA), and to investigate the association between them and iron status parameters.@*METHODS@#The study consisted of 65 child-bearing women (35 with iron deficiency anemia and 30 age-matched healthy women). The levels of serum iron were detected by using automated chemistry analyzer, the contents of serum ferritin were detected by electrochemiluminescence immunoassay, and the levels of serum erythroferrone and hepcidin were detected by specific enzyme-linked immunosorbent assay (ELISA) kit. The quantitative variables between two groups were compared and analyzed by SPSS22.0 software. Spearman correlation was used to detect correlation between the parameters.@*RESULTS@#The levels of Hb, serum iron, ferritin and transferrin saturation were significantly decreased in IDA patients as compared with in control group (P0.05). In IDA patients, serum hepcidin concentrations were positively correlated with hemoglobin concentration, serum iron, serum ferritin and transferrin saturation (r=0.448, r=0.496, r=0.754, r=0.491). But, serum erythroferrone concentrations showed no correlation with hemoglobin concentration, serum iron, serum ferritin, transferrin saturation and hepcidin (P>0.05).@*CONCLUSION@#Serum hepcidin levels were significantly decreased in child-bearing women with IDA, but the serum erythroferrone levels were not obviously different between two groups, suggesting that serum erythroferrone may be not involved in the regulation of iron metabolism in child-bearing women with mild and moderate IDA.

Urine hepcidin, netrin-1, neutrophil gelatinase-associated lipocalin and C-C motif chemokine ligand 2 levels in multicystic dysplastic kidney / Níveis de hepcidina, netrina-1, lipocalina associada a gelatinase neutrofílica e ligante de quimiocina C-C motif na urina do rim displásico multicístico

ABSTRACT Introduction: Glomerular hyperfiltration may lead to proteinuria and chronic kidney disease in unilateral multicystic dysplastic kidney (MCDK). We aimed to investigate the urine neutrophil-gelatinase-associated lipocalin (NGAL), netrin-1, hepcidin, and C-C motif chemokine ligand-2 (MCP-1/CCL-2) levels in patients with MCDK. Methods: Thirty-two patients and 25 controls were included. The urine hepcidin, netrin-1, NGAL, and MCP-1/CCL-2 levels were determined by ELISA. Results: The patients had higher serum creatinine (Cr) levels, urine albumin, and netrin-1/Cr ratio with lower GFR. There were positive correlations between urine protein/Cr, MCP-1/CCL-2/Cr, and netrin-1 with NGAL (r = 0.397, p = 0.031; r = 0.437, p = 0.041, r = 0.323, p = 0.042, respectively). Urine netrin-1/Cr was positively correlated with MCP-1/CCL-2/Cr (r = 0.356, p = 0.045). There were positive associations between the presence of proteinuria and netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr [Odds ratio (OR): 1.423, p = 0.037, OR: 1.553, p = 0.033, OR: 2.112, p = 0.027, respectively)]. ROC curve analysis showed that netrin-1/Cr, MCP-1/CCL-2/Cr, and NGAL/Cr had high predictive values for determining proteinuria p = 0.027, p = 0.041, p = 0.035, respectively). Urine hepcidin/Cr was negatively correlated with tubular phosphorus reabsorption and was positively correlated with urine NGAL/Cr (r = -0.418, p = 0.019; r = 0.682, p = 0.000; respectively). Conclusions: MCP-1/CCL-2 may play a role in the development of proteinuria in MCDK. Netrin-1 may be a protective factor against proteinuria-induced renal injury. Urine hepcidin/Cr may reflect proximal tubule damage in MCDK. Urine NGAL/Cr may be a predictor of tubule damage by proteinuria.

Resumo Introdução: A hiperfiltração glomerular pode causar proteinúria e doença renal crônica no rim displásico multicístico unilateral (RDM). Nosso objetivo foi investigar os níveis de lipocalina associada à gelatinase neutrofílica na urina (NGAL), netrina-1, hepcidina e quimiocina C-C com ligante-2 (MCP-1/CCL-2) em pacientes com RDM. Métodos: Trinta e dois pacientes e 25 controles foram incluídos. Os níveis urinários de hepcidina, netrin-1, NGAL e MCP-1/CCL-2 foram determinados por ELISA. Resultados: Os pacientes apresentaram níveis séricos mais elevados de creatinina (Cr), albumina na urina e relação netrina-1/Cr com menor TFG. Houve correlação positiva entre proteína na urina/Cr, MCP-1/CCL-2/Cr e netrina-1 com NGAL (r = 0,397, p = 0,031; r = 0,437, p = 0,041, r = 0,323, p = 0,042, respectivamente). A netrina-1/Cr na urina foi correlacionada positivamente com MCP-1/CCL-2/Cr (r = 0,356, p = 0,045). Houve associações positivas entre a presença de proteinúria e netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr [Odds ratio (OR): 1,423, p = 0,037, OR: 1,553, p = 0,033, OR: 2,112, p = 0,027, respectivamente) ]. A análise da curva ROC mostrou que netrina-1/Cr, MCP-1/CCL-2/Cr e NGAL/Cr apresentaram altos valores preditivos para determinar a proteinúria p = 0,027, p = 0,041, p = 0,035, respectivamente). A hepcidina/Cr na urina foi correlacionada negativamente com a reabsorção tubular de fósforo e positivamente com a NGAL/Cr na urina (r = -0,418, p = 0,019; r = 0,682, p = 0,000; respectivamente). Conclusões: MCP-1/CCL-2 pode ter participação no desenvolvimento de proteinúria no RDM. A Netrina-1 pode ser um fator protetor contra lesão renal induzida por proteinúria. Hepcidina/Cr na urina pode refletir danos em túbulos proximais no RDM. O valor de NGAL/Cr urinário pode ser um preditor de danos nos túbulos por proteinúria.

The effect of hepcidin on components of metabolic syndrome in chronic kidney disease: a cross-sectional study

SUMMARY BACKGROUND Hepcidin is an important regulator of iron homeostasis. OBJECTIVES This cross-sectional study was conducted to evaluate the association between hepcidin and components of metabolic syndrome in patients with chronic kidney disease (CKD). DESIGN AND SETTING 103 CKD patients and 59 healthy volunteers were included in the study from the University Hospital. METHODS Serum hepcidin levels were measured by enyzme-linked immunosorbent assay (ELISA) test. As for the study parameters, age, sex, body mass index, renal diseases, serum biochemistry, complete blood count, iron and total iron-binding capacity, ferritin, high-sensitive C-reactive protein (hsCRP), C- reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were evaluated. RESULTS The mean age of the patients was 58.63 ± 11.8 years. Hepcidin level was significantly associated with hypertension and higher uric acid levels (P < 0.05). There was a positive correlation between hepcidin and urea, uric acid, creatinine, ferritin, CRP, ESR, phosphorus, triglyceride, low-density lipoprotein (LDL), proteinuria and albuminuria in 24-hour urine collection. A negative correlation was found between hepcidin and estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, calcium, 25 OH vitamin D, pH, and bicarbonate levels. CONCLUSION Hepcidin, a well-known hormone regulator of iron metabolism, may play an important role in the pathogenesis of metabolic syndrome in patients with CKD, and further studies might delineate in-depth its potential as a promising early marker in these patients.

RESUMO FUNDAMENTO A hepcidina é um importante regulador da homeostase do ferro. OBJETIVOS Este estudo transversal foi realizado para avaliar a associação entre hepcidina e componentes da síndrome metabólica em pacientes com doença renal crônica (DRC). PROJETO E LOCAL Cento e três pacientes com DRC e 59 voluntários saudáveis foram incluídos no estudo no Hospital Universitário. MÉTODOS Os níveis séricos de hepcidina foram medidos pelo teste imunoenzimático (Elisa). Quanto aos parâmetros do estudo, idade, sexo, índice de massa corporal, doenças renais, bioquímica sérica, hemograma completo, capacidade de ligação total de ferro e ferro, ferritina, proteína C reativa altamente sensível (hsCRP), proteína C reativa (PCR) e taxa de sedimentação de eritrócitos (VHS) foram avaliados. RESULTADOS A idade média dos pacientes foi de 58,63±11,8 anos. Número de pacientes em cada estágio da DRC, do estágio I ao estágio V (não em terapia renal substitutiva). O nível de hepcidina foi significativamente associado à hipertensão e níveis mais altos de ácido úrico (P <0,05). Houve correlação positiva entre hepcidina e ureia, ácido úrico, creatinina, ferritina, PCR, VHS, fósforo, triglicerídeo, lipoproteína de baixa densidade (LDL), proteinúria e albuminúria na coleta de urina de 24 horas. Foi encontrada correlação negativa entre hepcidina e taxa de filtração glomerular estimada (TFGe), hemoglobina, hematócrito, cálcio, 25 OH de vitamina D, pH e níveis de bicarbonato. CONCLUSÃO A hepcidina é um hormônio bem conhecido que regula o metabolismo do ferro, mas também pode ser um importante contribuinte para os componentes da síndrome metabólica em pacientes com DRC.

Change of Hepcidin in Patients with Iron Overload at the Tibet Plateau / 中国实验血液学杂志

OBJECTIVE@#To explore the possible etiological factors of iron overload through detecting plasma hepcidin level of adult males at Tibet plateau.@*METHODS@#81 Tibetan male adult patients hospitalized in our department during January 2017 - December 2018 were selected, and divided into iron overload group and non-iron overload group. The difference in serum ferritin, serum iron, total iron binding capacity, hemoglobin, HBSAg, ALT, AST, albumin, creatinine and hepcidin of patients in each group were tested. To analyze the differences between groups. The regression analysis was applied to analyze the relationship between laboratory index and hepcidin.@*RESULTS@#The plasma hepcidin of iron overload group was significantly higher than that of the non-iron overload group [93.69 (65.57-133.92) ng/ml vs 63.93 (40.01-90.65) ng/ml] (P=0.005). And there was a positive correlation between plasma hepcidin and ferritin (β=0.03 ng/ml，95%CI 0.01-0.05) (P<0.01) and BMI (β=5.71 ng/ml，95%CI 0.54-10.88) (P<0.05）.@*CONCLUSION@#Iron overload at Tibet plateau can not be attributed to hepcidin deficiency in Tibetan adult male patients. Iron metabolism disorders in Tibetan population may be associated with metabolic syndrome.

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

Hepcidin as a Biomarker of Cardiorenal Syndrome

No abstract available.

Hepcidin and Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for Acute Kidney Injury Linked Iron Metabolism

No abstract available.

Urinary Biomarkers may Complement the Cleveland Score for Prediction of Adverse Kidney Events After Cardiac Surgery: A Pilot Study

BACKGROUND: The ability of urinary biomarkers to complement established clinical risk prediction models for postoperative adverse kidney events is unclear. We assessed the effect of urinary biomarkers linked to suspected pathogenesis of cardiac surgery-induced acute kidney injury (AKI) on the performance of the Cleveland Score, a risk assessment model for postoperative adverse kidney events. METHODS: This pilot study included 100 patients who underwent open-heart surgery. We determined improvements to the Cleveland Score when adding urinary biomarkers measured using clinical laboratory platforms (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-6) and those in the preclinical stage (hepcidin-25, midkine, alpha-1 microglobulin), all sampled immediately post-surgery. The primary endpoint was major adverse kidney events (MAKE), and the secondary endpoint was AKI. We performed ROC curve analysis, assessed baseline model performance (odds ratios [OR], 95% CI), and carried out statistical reclassification analyses to assess model improvement. RESULTS: NGAL (OR [95% CI] per 20 concentration-units wherever applicable): (1.07 [1.01–1.14]), Interleukin-6 (1.51 [1.01–2.26]), midkine (1.01 [1.00–1.02]), 1-hepcidin-25 (1.08 [1.00–1.17]), and NGAL/hepcidin-ratio (2.91 [1.30–6.49]) were independent predictors of MAKE and AKI (1.38 [1.03–1.85], 1.08 [1.01–1.15], 1.01 [1.00–1.02], 1.09 [1.01–1.18], and 3.45 [1.54–7.72]). Category-free net reclassification improvement identified interleukin-6 as a model-improving biomarker for MAKE and NGAL for AKI. However, only NGAL/hepcidin-25 improved model performance for event- and event-free patients for MAKE and AKI. CONCLUSIONS: NGAL and interleukin-6 measured immediately post cardiac surgery may complement the Cleveland Score. The combination of biomarkers with hepcidin-25 may further improve diagnostic discrimination.

Predicting hepcidin level using inflammation markers and iron indicators in patients with anemia of chronic disease

ABSTRACT Background: Recently, a small peptide called Hepcidin, was found to have an important role in regulating the iron metabolism in anemia of chronic disease (ACD) patients. Hepcidin is regulated by a variety of conditions at the transcriptional level. Therefore, our study aims to predict the level of hepcidin serum using inflammation markers and iron indicators in patients afflicted with ACD and observe how this severity of inflammation separated the level of interleukin-6 (IL-6), as well the as hepcidin level. Methods: A cross-sectional data analysis was conducted on 80 ACD adult patients treated at the Sanglah Teaching Hospital in Bali, Indonesia. We used hepcidin serum and several markers, such as the hemoglobin level, inflammation markers, renal function tests, IL-6, and iron indicators, to predict the hepcidin level. Results: This study recruited 80 ACD patients, comprising 45 men (56.3%) and 35 women (43.7%). The mean age of the participants was 43 ± 16.5 years. Only IL-6, ferritin and serum creatinine correlate significantly with serum hepcidin from seven variables that were previously eligible to enter the analysis. This study found the model to predict the hepcidin level using IL-6 ferritin and the creatinine level as the hepcidin level (predicted) = −23.76 + 0.396 (IL 6) + 0.448 (ferritin) + 0.310 (creatinine). Conclusion: This study has revealed that the creatinine level, ferritin and IL-6 can be used to predict the hepcidin level in patients with anemia of chronic disease. It is to be hoped that further cohort studies can validate our formula to predict the hepcidin level.

Increased Serum Hepcidin Levels in Children and Adolescents with Attention Deficit Hyperactivity Disorder

OBJECTIVE: In this study, we aimed to evaluate the serum hepcidin levels in attention deficit hyperactivity disorder (ADHD) patients that were newly diagnosed with no history of psychotropic drugs. METHODS: A total of 70 ADHD patients and 69 healthy controls were enrolled in our study. During the diagnosis, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version were applied. The sociodemographic data form, Turgay DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale, and Conners’ Rating Scales-Revised: Long Form were used for the clinical evaluation. Serum hepcidin levels were measured and compared between the groups. RESULTS: No significant difference between the groups in terms of age (p=0.533) and gender (p=0.397) was determined. In addition, the groups did not differ significantly for the other sociodemographic variables recorded. Serum hepcidin levels were found to be significantly higher in the patients with ADHD than healthy controls (p=0.019). CONCLUSION: To the best of our knowledge, this study is the first to evaluate the total serum hepcidin levels in ADHD patients. Our study findings may suggest that high levels of hepcidin may cause iron dysregulation in ADHD patients. However, further studies are required to establish a definite conclusion.

The effect of nonsurgical periodontal therapy on hepcidin and on inflammatory and iron marker levels

Abstract Serum hepcidin levels may increase in response to infection and inflammation. The present study investigated the effect of nonsurgical periodontal therapy (NSPT) on levels of serum hepcidin, inflammatory markers, and iron markers. An interventional study was conducted on 67 patients (age 30-65 years) without other diseases, except for chronic periodontitis (CP). Patients were allocated to either CP or control groups. The CP group received supragingival and subgingival scaling and root planing procedures, whereas the control group received supragingival scaling. Probing depth (PD), bleeding on probing, clinical attachment level (CAL), visible plaque index (VPI), serum hepcidin and interleukin-6 (IL-6) levels, high-sensitivity C-reactive protein (hs-CRP), hematological markers, and iron markers were measured at baseline and at 90 days after NSPT. The CP group had statistically significant lower mean values for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) (p ≤ 0.05). The control group had statistically significant reductions in hemoglobin, hematocrit, MCV, and MCH (p ≤ 0.05). Serum hepcidin, IL-6, and erythrocyte sedimentation rate (ESR) levels were significantly decreased in both groups after NSPT. Periodontal markers were more markedly reduced in the CP group compared with the control group (p ≤ 0.05). These findings suggest that NSPT may reduce the serum levels of IL-6, hepcidin, and periodontal parameters.

Hepcidin-orchestrated Hemogram and Iron Homeostatic Patterns in Two Models of Subchronic Hepatic injury / 生物医学与环境科学（英文）

OBJECTIVE@#This study was designed to evaluate hematological disorders and the orchestrating roles of hepcidin and IL-6 in rat models of thioacetamide (TAA) and carbon tetrachloride (CCl4) hepatotoxicity.@*METHODS@#Rats were intraperitoneally injected with TAA (10 mg/100 g rat weight dissolved in isosaline) or CCl4 (100 μL/100 g rat weight diluted as 1:4 in corn oil) twice weekly for eight consecutive weeks to induce subchronic liver fibrosis. Blood and tissue samples were collected and analyzed.@*RESULTS@#CCl4 but not TAA significantly decreased the RBCs, Hb, PCV, and MCV values with minimal alterations in other erythrocytic indices. Both hepatotoxins showed leukocytosis, granulocytosis, and thrombocytopenia. By the end of the experiment, the erythropoietin level increased in the CCl4 model. The serum iron, UIBC, TIBC, transferrin saturation%, and serum transferrin concentration values significantly decreased, whereas that of ferritin increased in the CCl4 model. TAA increased the iron parameters toward iron overload. RT-PCR analysis revealed increased expression of hepatic hepcidin and IL-6 mRNAs in the CCl4 model and suppressed hepcidin expression without significant effect on IL-6 in the TAA model.@*CONCLUSION@#These data suggest differences driven by hepcidin and IL-6 expression between CCl4 and TAA liver fibrosis models and are of clinical importance for diagnosis and therapeutics of liver diseases.

Role of redox iron towards an increase in mortality among patients: a systemic review and meta-analysis

An increase in biochemical concentrations of non-transferrin bound iron (NTBI) within the patients with an increase in serum iron concentration was evaluated with the following objectives: (a) Iron overloading diseases/conditions with free radicle form of ‘iron containing’ reactive oxygen species (ROS) and its imbalance mediated mortality, and (b) Intervention with iron containing drugs in context to increased redox iron concentration and treatment induced mortality. Literature search was done within Pubmed and cochrane review articles. The Redox iron levels are increased during dys-erythropoiesis and among transfusion recipient population and are responsive to iron-chelation therapy. Near expiry ‘stored blood units’ show a significant rise in the ROS level. Iron mediated ROS damage may be estimated by the serum antioxidant level, and show reduction in toxicity with high antioxidant, low pro-oxidant levels. Iron drug therapy causes a significant increase in NTBI and labile iron levels. Hospitalized patients on iron therapy however show a lower mortality rate. Serum ferritin is a mortality indicator among the high-dose iron therapy and transfusion dependent population. The cumulative difference of pre-chelation to post chelation ROS iron level was 0.97 (0.62; 1.32; N=261) among the transfusion dependent subjects and 2.89 (1.81–3.98; N=130) in the post iron therapy ‘iron ROS’ group. In conclusion, iron mediated mortality may not be mediated by redox iron among multi-transfused and iron overloaded patients.

New Oral Agent for Treatment of Anemia in Patient with Chronic Kidney Disease: Prolyl Hydroxylase Inhibitor / 대한내과학회지

Hypoxia inducible factor (HIF)-stabilizers are being developed for the renal anemia treatment. This small molecules inhibit prolyl hydroxylase domain (PHD)-containing enzymes, causing HIF activation instead of degradation under the state of normoxia, finally increase production of intrinsic erythropoiesis. Current treatment guidelines suggest that renal anemia should be treated mainly with iron and erythropoiesis stimulating agents (ESAs). But there are several complications and concerns such as hypertension, ESA refractory anemia and increased cardiovascular mortality in using ESAs. Advantages of HIF stabilizers over ESAs are orally available, no dose-up requirement for inflammation. So far new HIF stabilizers showed efficacy and safety in renal anemia treatment. This new therapeutic agent may emerge as a standard treatment option for renal anmia treatment.

Hepcidin serum levels in HCV chronically mono-infected naïve patients, compared to healthy individuals

Introduction: Metabolism of iron is altered in patients infected with chronically Hepatitis C. The aim of this study is to compare compare the hepcidin levels in between individuais chronically infected with HCV and uninfected individuals. The aim of this study is to compare the hepcidin serum levels between individuals chronically infected with HCV and uninfected individuals. Methods: A cross-sectional study evaluating hepcidin serum levels of mono-infected HCV (n=29), naive, non-diabetic, non-cirrhotic and non-obese patients by means of ELISA, compared to uninfected patients (n=9) with the same characteristics. The degree of liver fibrosis, according to the METAVIR scale on liver biopsies, the lipid profile, the resistance insulin level, as calculated on HOMA-IR (homeostatic model assessment for insulin resistance), the interleukin-6 (IL-6) and the ferritin serum levels were also measured. Results: The levels of hepcidin were significantly lower in HCV patients compared to controls (8.4 pg/mL (±4.94) vs. 19.51 pg/mL (±5.51)) with p<0.001. The levels of ferritin and hepcidin did not show any relation. There was no difference between hepcidin levels in relation to viral genotype, viral load, IL-6 and degrees of fibrosis within HCV infected individuals. Conclusion: It is possible that hepatic iron overload in this population is explained by suppressed levels of hepcidin in patients with HCV. (AU)

Basic Understanding of Iron Metabolism / 임상소아혈액종양

Iron is critical for almost all living organisms because it serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism. Disruption of iron homeostasis is associated with a wide range of diseases. Thus mammals have developed sophisticated mechanisms to maintain optimal range of iron concentration. Iron regulation involves processes at the systemic and cellular levels. These processes are regulated by hepcidin and iron regulatory proteins. Hepcidin modulates systemic iron homeostasis with ability to impede cellular iron export via interaction with the iron export protein, ferroportin. Whereas, iron regulatory proteins control cellular iron homeostasis by translational regulation of proteins which involve iron metabolism. Recent advances in the study of iron metabolism have shown promising results that hepcidin-targeted strategies may help to improve the diagnosis and treatment of iron related diseases. Although these strategies are now under development, ongoing studies can help to elucidate its application possibilities.

Hepcidina: la llave del metabolismo del hierro / Hepcidin: the key of iron metabolism / Hepcidina: a chave do metabolismo do ferro

En las últimas décadas se ha avanzado en el conocimiento de la regulación del metabolismo del Hierro (Fe). La Hepcidina (Hp), producida por los hepatocitos, regula la absorción de hierro desde el tubo digestivo y la liberación desde los depósitos del sistema macrofágico y del hígado. En caso de deficiencia de Fe, la Hp está disminuida entregando Fe a la transferrina (Tf). El aumento de Fe y de las citoquinas de la inflamación estimulan la producción de Hp. El ejecutor de la Hp es la Ferroportina (FP), único exportador de Fe. Hay reguladores naturales de la Hp, como la Matriptasa 2. Las mutaciones que limitan su expresión inducen dificultades en la disponibilidad de Fe (IRIDA, sobrecarga de Fe). En los últimos años se ha identificado la Eritroferrona, producida por los eritroblastos activos en la eritropoyesis. Inhibe la síntesis de Hp, permitiendo la liberación del hierro de los depósitos y su absorción por el tubo digestivo, para facilitar la disponibilidad de Fe para la eritropoyesis. Aún no está definido cómo se podrán utilizar estos elementos en el campo diagnóstico, su estandarización y su aplicación terapéutica, pero es probable que resulten de gran utilidad.

In the last decades, a lot of progress has been made on the knowledge of iron (Fe) metabolism regulation. Hepcidin (Hp) is produced by hepatocytes and it regulates the iron absorption from the duodenum and the liberation from macrophages and from the liver. When there is iron deficiency, Hp, which delivers iron to transferrin (Tf), is low. Iron overload and inflammation cytokines stimulate Hp production. The Hp natural executor is Ferroportin (FP), which is the only iron exporter from the cells. One of the natural regulators of Hp is Matriptasa 2, which down regulates Hp. Mutations that limit their expression induce iron overload and anemia (IRIDA). In the last few years, Erythroferrone (ERFE) was discovered. ERFE is produced by active erythroblasts: it inhibits Hp synthesis, allowing the iron liberation from deposits and its duodenal absorption, and also the iron release from macrophages facilitating the erythroid production. The erythroblastic activity, even ineffective, acts as a stimulus of ERFE synthesis. Until now, it has not been defined yethow these different variables could be used for diagnosis, its standardization, or for therapeutic applications, but it is highly probable that they will improve our knowledge and managements kills in this field.

Nas últimas décadas háavanços no conhecimento da regulação do metabolismo do Ferro (Fe). A Hepcidina (Hp), produzida pelos hepatócitos, regula a absorção do ferro desde o tubo digestivo e a liberação desde os depósitos do sistema macrofágico e do fígado. Em caso de deficiência de Fe, a Hp está diminuída entregando Fe à transferrina (Tf). O aumento de Fe e as citoquinas da inflamação estimulam a produção de Hp. O executor da Hp é a Ferroportina (Fp), único exportador de Fe. Há reguladores naturais da Hp, como a Matriptase 2. As mutações que limitam sua expressão induzem dificultades na disponibilidade de Fe (IRIDA, sobrecarga de Fe). Nos últimos anos se identificou que a Eritroferrona, produzida pelos eritroblastosativos na eritropoiese inibe a síntese de Hp, permitindo a liberação de ferro dos depósitos e a absorção pelo tubo digestivo, para facilitar a disponibilidade de Fe para a eritropoiese. Ain da não sedefiniu como poderãoser utilizadosestes elementos no campo diagnóstico, sua padronização e sua aplicação terapêutica, mas é provável que sejam de grande utilidade.

Prohepcidina y estado del hierro e inflamación en escolares sanos o H. pylori positivos asintomáticos / Prohepcidine iron status and inflammation in healthy and asymptomatic H. pylori school children / Pró-hepcidina estado de ferro e inflamação em estudantes saudáveis ou H. pylori positivos assintomáticos

El eje hepcidina-ferroportina es determinante en la homeostasis del hierro. Niveles elevados de hepcidina reducen la capacidad de absorción intestinal del hierro, así como su movilización entre tejidos. Una condición que produce valores séricos elevados de hepcidina es la infección. Como la infección con Helicobacter pylori (Hp) predispone a una deficiencia de hierro, en este estudio se evaluaron los niveles séricos de Pro-Hepcidina (PH), un precursor de la hepcidina, en un grupo de escolares asintomáticos, infectados con Hp (80 niños) y se los comparó con un grupo similar de niños sanos (59 niños). Los resultados mostraron que los niños infectados en los que se detectó la presencia de Hp (test de aire espirado) tenían valores de proteína C reactiva (PCR) significativamente más altos que los niños sanos. Ambos grupos presentaron valores similares de: adecuación de la ingesta de hierro, ferritina sérica (Fs), hemoglobina, hematocrito, receptores solubles de transferrina. La prevalencia de anemia y deficiencia subclínica de hierro en el grupo total (infectados + no infectados) fue de 10 y 60%, respectivamente sin diferencias entre los grupos. Sin embargo, en el grupo de niños sanos la PH sérica correlacionó significativamente (r=0,730/p<0,001) con los niveles de Fs, mientras que en los niños infectados, los niveles de PH no correlacionaron con la Fs, pero correlacionaron con la severidad de la infección (r=0,52/p<0,001). Esta tendencia de la PH a aumentar con la severidad de la infección podría explicar la mayor prevalencia de deficiencia de hierro en pacientes infectados con Hp.

The hepcidin-ferroportin axis is crucial in iron homeostasis. High serum hepcidine reduces iron intestinal absorption and tissue iron mobilization. Infection and inflammation increase serum hepcidin, predisposing to iron deficiency. Since Helicobacter pylori (Hp) infection has been associated to iron deficiency, the serum levels of prohepcidin PH (a precursor of hepcidin) were evaluated in 80 school children infected with Hp but without gastric symptoms. This was compared with PH levels in a group of 59 non Hp infected children. The results showed that infected children (exhaled air method) had higher levels of protein C reactive protein (CRP) than the non-infected group. Both groups had similar levels of iron consumption, serum ferritin (Fs), hemoglobin, hematocrit, soluble transferrin receptors and PH. The prevalence of anemia and of subclinical iron deficiency in the whole group (infected + non-infected) reached 10 and 60% respectively with no differences between groups. However, in the group of non-infected children, serum PH correlated (r=0.730/ p<0.001) with Fs levels whereas in the infected children, PH did not correlate with Fs but it correlated with the severity of the infection (r = 0.52/p<0.001). The tendency of PH to increase with the severity of infection could explain the higher prevalence of iron deficiency seen in Hp infection.

O eixo hepcidina-ferroportina é determinante na homeostase do ferro. Níveis elevados de hepcidina reduzem a capacidade de absorção intestinal do ferro, bem como sua mobilização entre tecidos. Uma condição que produz valores séricos elevados de hepcidina é a infecção. Como a infecção pelo Helicobacter pylori (Hp) predispõe a uma deficiência de ferro, neste estudo foram avaliados os níveis séricos de Pro-hepcidina (PH), um precursor da hepcidina em um grupo de estudantes assintomáticos infectados com Hp (80 crianças) e foram comparados com um grupo similar de crianças saudáveis (59 crianças). Os resultados mostraram que as crianças infectadas em que se detectou a presença de Hp (método de ar exalado) tinham valores de proteína C-reativa (PCR) significativamente mais elevada do que as crianças saudáveis. Ambos os grupos tiveram valores semelhantes de adequação da ingestão de ferro, ferritina sérica (Fs), hemoglobina, hematócrito, receptores solúveis de transferrina. A prevalência de anemia e deficiência subclínica de ferro no grupo total (infectados + não infectados) foi de 10 e 60%, respectivamente, sem diferenças entre os grupos. No entanto, no grupo de crianças saudáveis a PH sérica correlacionou significativamente (r=0,730/p<0,001) com os níveis de Fs, ao passo que em crianças infectadas, os níveis de PH não correlacionaram com a Fs, mas correlacionaram com a gravidade da infecção (r=0,52/p<0,001). Esta tendência da PH a aumentar com a gravidade da infecção poderia explicar a elevada prevalência de deficiência de ferro em pacientes infectados com Hp.