Abstract
BackgroundAnemia is very common in patients with human immunodeficiency virus (HIV)–associated tuberculosis, and hepcidin may be key in mediating this. We explored the relationship between blood hepcidin concentrations and anemia severity, mycobacterial burden and mortality in patients with HIV-associated tuberculosis.MethodsConsecutive unselected HIV-infected adults in South Africa were systematically investigated for tuberculosis. Three groups were studied: 116 hospitalized inpatients with HIV infection and tuberculosis (hereafter, “hospitalized patients”), 58 ambulatory outpatients with HIV infection and newly diagnosed tuberculosis (hereafter, “ambulatory patients with tuberculosis”), and 58 ambulatory outpatients with HIV infection and without tuberculosis (hereafter, “ambulatory patients without tuberculosis”). Blood hepcidin concentrations were determined for all patients. Vital status at 3 months was determined, and independent predictors of mortality were identified.ResultsMedian hepcidin concentrations were 38.8 ng/mL among hospitalized patients, 19.1 ng/mL among ambulatory patients with tuberculosis, and 5.9 ng/mL among ambulatory patients without tuberculosis (P < .001). In both groups with HIV-associated tuberculosis, hepcidin concentrations were strongly associated with greater anemia severity. Additionally, strong, graded associations were observed between hepcidin and composite indices of mycobacterial burden and dissemination. Patients dying within 3 months had significantly higher hepcidin concentrations, which independently predicted mortality.ConclusionsHigh hepcidin concentrations were strongly associated with disseminated disease, anemia, and poor prognosis in patients with HIV-associated tuberculosis. Hepcidin may be a mechanistically important mediator underlying the high prevalence of severe anemia in these patients.
Highlights
Anemia is very common in patients with human immunodeficiency virus (HIV)–associated tuberculosis, and hepcidin may be key in mediating this
Median hepcidin concentrations were 38.8 ng/mL among hospitalized patients, 19.1 ng/mL among ambulatory patients with tuberculosis, and 5.9 ng/mL among ambulatory patients without tuberculosis (P < .001). In both groups with HIV-associated tuberculosis, hepcidin concentrations were strongly associated with greater anemia severity
High hepcidin concentrations were strongly associated with disseminated disease, anemia, and poor prognosis in patients with HIV-associated tuberculosis
Summary
Consecutive unselected HIV-infected adults in South Africa were systematically investigated for tuberculosis. All patients were unselected and consecutively recruited as part of two previously reported studies of tuberculosis diagnostic analyses [23, 24], and most resided in the township communities of Cape Town, where there is a large tuberculosis burden [25, 26]. These studies were approved by the research ethics committees of the University of Cape Town and the London School of Hygiene and Tropical Medicine. These patients were eligible for inclusion in the present study if they were found to have a new microbiologically confirmed diagnosis of tuberculosis, had a frozen plasma sample available for laboratory measurements, and had not had a blood transfusion within the 120-day period (the approximate life span of red blood cells) prior to study entry
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