Relationship Between Hepcidin, Iron Metabolism, Inflammation and Hypersplenism in Anaemia of Kala-Azar

Kala-azar, or visceral leishmaniasis (VL), is a parasitic disease caused by Leishmania spp., characterised by fever, weight loss, splenomegaly, hepatomegaly, and anaemia. This study evaluated the relationship between hepcidin, inflammation, iron metabolism, and hypersplenism in VL-associated anaemia. In this cross-sectional study, confirmed VL patients without recent transfusions were assessed. Haematological and inflammatory parameters were analysed using correlation and multivariate regression tests. Anaemia was present in 95.2% of the sample, predominantly normocytic (59.5%) and normochromic (76.2%), or microcytic (40.5%) and hypochromic (23.8%). Inflammatory markers were markedly elevated in most patients, particularly hepcidin, which was increased in 97.6% of cases (median: 351.46 ng/mL), suggesting persistent inflammation and impaired iron bioavailability. However, IL-6, CRP, and ferritin showed weak to moderate negative correlations with hepcidin (ρ = -0.33, ρ = -0.66, and ρ = -0.30, respectively). These findings highlight the complex interplay between anaemia and inflammation in kala-azar, with elevated hepcidin levels and paradoxical correlations with inflammatory markers. They underscore the central role of splenomegaly in VL-related anaemia and suggest potential contributions from other factors affecting iron metabolism, such as erythropoietin and erythroferrone. Understanding the dynamics of these markers throughout disease progression and treatment may further elucidate the pathophysiology of VL and support the development of targeted therapies.