Hepcidin is a key mediator of anemia of inflammation in Crohn's disease

Basseri, Robert J.; Nemeth, Elizabeta; Vassilaki, Maria; Basseri, Benjamin; Enayati, Pedram; Shaye, Omid; Bourikas, Leonidas A.; Ganz, Tom; Papadakis, Konstantinos A.

doi:10.1016/j.crohns.2012.10.013

Cited by 62 publications

(46 citation statements)

References 29 publications

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“…31 Increased hepcidin levels have been detected in patients with anemia associated with chronic inflammatory diseases, such as inflammatory bowel disease, chronic kidney disease, and hematologic cancers. [32][33][34][35] Our data showed that hepcidin was inversely correlated with Hb, particularly in patients with advanced cancer. High hepcidin levels were associated with higher ferritin, lower serum iron, and lower transferrin saturation levels.…”

Section: Discussionmentioning

confidence: 50%

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The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study

Macciò

Madeddu

Gramignano³

et al. 2014

Haematologica

190

144

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ABSTRACTfore, essential to analyze all these factors that cause anemia, particularly before beginning any form of therapy that may worsen anemia.The aim of this work was to document the prevalence of anemia in a large cohort of patients with solid tumors before any exposure to antineoplastic treatment, and to assess the possible correlation between Hb levels and the commonly used indices of inflammation, malnutrition, and metabolic stress. We hypothesized that inflammation and malnutrition are independent predictors of the development and severity of anemia and that a better knowledge of CRA may enable its more adequate treatment. MethodsThis study was a prospective, observational trial performed in accordance with the Helsinki declaration after approval by the Local Institutional Ethics Committee. Between May 2011 and January 2014, 888 consecutive patients with histologically confirmed solid cancer at different sites referred to the Departments of Obstetrics and Gynecology, Sirai Hospital, Carbonia, Medical Oncology at "N.S. Bonaria" Hospital, San Gavino, "Nuova Casa di Cura", Decimomannu, and "A. Businco" Hospital, Cagliari, Italy, were enrolled. Table 1 reports the participants' clinical characteristics. Patients were assessed at diagnosis before receiving any cancer treatment. Exclusion criteria were: evidence of infections, chronic inflammatory disease, active bleeding, hemolysis, renal insufficiency, or hypothyroidism; known history of hematologic disorders (including hemoglobinopathies), family history of thalassemia or hemocromatosis; treatment with EPO, i.v. iron or blood transfusion in the preceding 12 weeks; current iron, vitamin B12 or folate supplementation.Anemia was defined according to our laboratory populationbased normal ranges as Hb <13.0 g/dL for males and <12.0 g/dL for females. Karnofsky PS was categorized into four prognostic classes. 17 Blood samples were obtained at 8 a.m. after overnight fasting since serum hepcidin and iron levels show similar circadian changes. In accordance with Ganz et al., 18 the 8 a.m. fasting hepcidin concentrations were more consistent than those at other times of the day. After centrifugation of the blood samples, serum was stored at -80°C until analysis.In all patients Hb levels and parameters of chronic inflammation [CRP, fibrinogen, IL-6, IL-1β, tumor necrosis factor-α (TNFα)], iron metabolism (iron, ferritin, transferrin, hepcidin), EPO, nutritional status (albumin, leptin, cholesterol, HDL, LDL, triglycerides) and oxidative stress [ROS, glutathione peroxidase (GPx), superoxide dismutase (SOD)] were measured. The formula for expected EPO was: 2.5 x (140-Hb g/L). 19 Since leptin is highly dependent on body mass index (BMI), the leptin/BMI ratio was reported. The modified Glasgow prognostic score (mGPS) was calculated as follows: 2, both elevated CRP (≥10 mg/L) and low albumin (<3.5 g/dL); 1, elevated CRP only; 0, normal CRP (<10 mg/L). 20 Laboratory assaysRoutine analyses of Hb, CRP, fibrinogen, serum iron, transferrin, ferritin, triglycerides, cholesterol...

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Section: Discussionmentioning

confidence: 50%

“…[32][33][34][35] Our data showed that hepcidin was inversely correlated with Hb, particularly in patients with advanced cancer. High hepcidin levels were associated with higher ferritin, lower serum iron, and lower transferrin saturation levels.…”

mentioning

confidence: 50%

The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study

Macciò

Madeddu

Gramignano³

et al. 2014

Haematologica

190

144

View full text Add to dashboard Cite

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“…2,3 Hepcidin, a hormone produced in the liver, encoded in humans by Hepcidin Antimicrobial Peptide (HAMP) gene, is the primary regulator of iron homeostasis. [4][5][6] Since its discovery by Krause et al 7 and Park et al, 8 there has been an increased understanding of iron homeostasis and the role of hepcidin in ACD. Recently, several studies have been conducted to evaluate the role of hepcidin in various diseases and its diagnostic reliability in distinguishing IDA from ACD.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of hepcidin as a biomarker for the differential diagnosis of iron deficiency anaemia and anaemia of chronic disease

et al. 2018

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Background:Anaemia affects approximately 1.62 billion people globally corresponding to 24.8% of the world's population. Iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD) are the most common forms of anaemia. A hormone produced by the liver, hepcidin, is the primary regulator of iron homeostasis and its production increases in ACD and decreases in IDA. Usually, ACD and IDA coexist and sometimes look identical on peripheral blood smears. Aims and Objectives: The current study aims to evaluate the diagnostic value of hepcidin to predict ACD from IDA as well as the diagnostic value of hepcidin to predict ACD from a combination of IDA and ACD. Materials and Methods: Specimens presenting with haematological indices suggestive of IDA and/or ACD following World Health Organisation (WHO) standard case definitions were identified among samples coming to the Haematology laboratory for routine investigations. Serum hepcidin, serum ferritin, serum iron and total iron binding capacity (TIBC) were assessed. Demographic data was obtained from specimen requisition forms. Results: Of the 66 participants, 62.1% (n = 41) were females. IDA was more common among females (36.4%) than males (6.1%) while ACD was more common in males (19.7%) than females (12.1%). Iron Deficiency Anaemia participants had significantly lower hepcidin levels than ACD (p<0.001). There was a significant positive correlation between serum hepcidin and serum ferritin levels (p < 0.001). Conclusion: We found that IDA participants had significantly lower hepcidin levels than ACD and IDA/ACD combined. Therefore, serum hepcidin could be considered in diagnosing and distinguishing ACD from IDA or IDA/ACD as it also had high diagnostic sensitivity and specificity compared to other markers.

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“…110 The mechanism may involve a decreased production or sensitivity to erythropoietin, 20 inhibition of erythroid precursors 13 and disruption of the iron metabolism mediated by hepcidin. 111 Basseri et al 112 showed a correlation between high levels of IL-6, hepcidin and ferritin and the severity of anaemia.…”

Section: Rationalementioning

confidence: 99%

Portuguese Consensus on the Diagnosis, Prevention and Treatment of Anaemia in Inflammatory Bowel Disease

et al. 2016

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Introduction: Anaemia can be considered the most common extra-intestinal manifestation in inflammatory bowel disease. Nevertheless, anaemia is often under-diagnosed and under-treated both in adults and children with inflammatory bowel disease. Herein, we report the consensus statements on the management of anaemia in inflammatory bowel disease developed by the Portuguese Working Group on Inflammatory Bowel Disease (known as Grupo de Estudo da Doença Inflamatória Intestinal - GEDII) to aid clinicians in daily management of inflammatory bowel disease patients. Material and Methods: A comprehensive literature review was conducted in order to prepare consensus statements on the following topics: (1) prevalence and diagnosis of anaemia in inflammatory bowel disease, (2) iron supplementation for the prevention of anaemia in inflammatory bowel disease and (3) treatment of anaemia in inflammatory bowel disease. The final statements for each topic were discussed at a consensus meeting and rated according to the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence. Consensus: It was concluded that anaemia has a high incidence and prevalence in inflammatory bowel disease, particularly in those with active disease and hospitalised. Patients with anaemia had decreased quality of life and frequently complained of fatigue. Absolute indications for intravenous therapy should be considered: (1) moderate to severe anaemia (haemoglobin < 10.5 g/dL) or clearly symptomatic anaemia; (2) previous intolerance to oral iron supplements; (3) inappropriate response to oral iron; (4) active severe intestinal disease; (5) need for a quick therapeutic response (e.g. surgery in the short term); (6) concomitant therapy with erythropoiesis-stimulating agent; and (7) patient’s preference.

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Hepcidin is a key mediator of anemia of inflammation in Crohn's disease

Abstract: We demonstrate that ACD in CD is characterized by high serum IL-6 and hepcidin levels, which negatively correlate with Hgb levels. Our data support the hypothesis that IL-6-driven hepcidin production mediates ACD in patients with CD.

Cited by 62 publications

References 29 publications

The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study

The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study

Evaluation of hepcidin as a biomarker for the differential diagnosis of iron deficiency anaemia and anaemia of chronic disease

Portuguese Consensus on the Diagnosis, Prevention and Treatment of Anaemia in Inflammatory Bowel Disease

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