Hepcidin and conventional markers to detect iron deficiency in severely anaemic HIV-infected patients in Malawi

Abstract

phone: +265(0)883699070/ +31(0)616193631 35 Abstract 36 37 Introduction: Iron deficiency is a treatable cause of severe anaemia in low-and-middle-38 income-countries (LMIC). Diagnosing it remains challenging as peripheral blood markers 39 poorly reflect bone-marrow iron deficiency (BM-ID), especially in the context of HIV-40 infection.41 Methods: Severe anaemic (haemoglobin ≤70g/l) HIV-infected adults were recruited at 42 Queen Elizabeth Central Hospital, Blantyre, Malawi. BM-ID was evaluated. Accuracy of 43 blood markers including hepcidin alongside mean corpuscular volume, mean cellular 44 haemoglobin concentration, serum iron, serum ferritin, soluble transferrin receptor 45 (sTfR), sTfR -index, sTfR -ratio to detect BM-ID was valued by ROC area under the curve 46 (AUC ROC ).47 Results: Seventy-three patients were enrolled and 35 (48.0%) had BM-ID. Hepcidin and 48 MCV performed best; AUC ROC of 0.593 and 0.545. Other markers performed poorly 49 (ROC<0.5). The AUC ROC of hepcidin in males was 0.767 (sensitivity 80%, specificity 78%) 50 and in women 0.490 (sensitivity 60%, specificity 61%).51 Conclusion: BM-ID deficiency was common in severely anaemic HIV-infected patients 52 and is an important and potential treatable contributor to severe anaemia. Hepcidin was 53 the best, though still suboptimal, marker of BM-ID. Hepcidin, which is directly linked to 54 iron absorption, is a very promising marker to guide curative iron supplementation 55 policies in severely anaemic HIV-infected patients. 56 57 59 Introduction 60 Anaemia affects approximately a third of the world's population and substantially reduces the 61 disability-adjusted life years worldwide (1). Iron deficiency contributes to development of 62 anaemia and is diagnosed in more than half of all anaemic persons (2). Consequently, iron 63 supplements remain the backbone of prevention and treatment protocols for anaemia. 64Anaemia has an extensive list of potential causes. In sub-Saharan Africa, where this 65 condition is most common, its aetiology is even more complex and in these setting 66 aetiologies commonly co-incide requiring a multifactorial approach (3, 4). HIV may be the 67 cause of anaemia by its direct effect on BM cells, but can also increase the range of 68 aetiological factors to encompass opportunistic viral, bacterial and parasitic infections, 69 drugs such as Zidovudine and co-trimoxazole, micronutrient deficiencies and neoplastic 70 diseases (5, 6). 71The exact role of iron deficiency, one of the few potentially preventable and 72 treatable causes of anaemia, remains unclear due to its diagnostic challenges in HIV-73 infected patients in low resource settings (3, 4, 7). Peripheral blood markers, including 74 erythrocyte indices, serum iron, ferritin, and soluble transferrin receptor (sTfR), have 75 been evaluated but their accuracy is often negatively affected by inflammatory states and 76 renal and liver conditions, which are common in both the African and HIV-infected 77 populations (8-11). Previous studies therefore concluded that the ...