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Inverse relationship of serum hepcidin levels with CD4 cell counts in HIV-infected patients selected from an Indonesian prospective cohort study.

Wisaksana R, de Mast Q, Alisjahbana B, Jusuf H, Sudjana P, Indrati AR, Sumantri R, Swinkels D, van Crevel R, van der Ven A - PLoS ONE (2013)

Bottom Line: Iron parameters including hepcidin were compared using samples collected at cohort enrollment, and compared with recently published reference values for serum hepcidin.Cases had significantly higher hepcidin and ferritin concentrations at cohort enrollment compared to matched controls, but these differences were fully accounted for by the cases who started TB treatment between day 31 and 60 after enrollment.High serum hepcidin levels and hyperferritinemia were found in patients starting TB treatment shortly after cohort enrollment, suggesting that these parameters have a predictive value for development of manifest TB in HIV-infected patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine Faculty of Medicine, Padjadjaran University/Hasan Sadikin Hospital, Bandung, Indonesia ; Health Research Unit, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia.

ABSTRACT

Background: Distortion of iron homeostasis may contribute to the pathogenesis of human immunodeficiency virus (HIV) infection and tuberculosis (TB). We studied the association of the central iron-regulatory hormone hepcidin with the severity of HIV and the association between hepcidin and other markers of iron homeostasis with development of TB.

Methods: Three groups of patients were selected from a prospective cohort of HIV-infected subjects in Bandung, Indonesia. The first group consisted of HIV-infected patients who started TB treatment more than 30 days after cohort enrollment (cases). The second group consisted of HIV-infected patients who were matched for age, gender and CD4 cell count to the cases group (matched controls). The third group consisted of HIV-infected patients with CD4 cell counts above 200 cells/mm(3) (unmatched controls). Iron parameters including hepcidin were compared using samples collected at cohort enrollment, and compared with recently published reference values for serum hepcidin.

Results: A total of 127 HIV-infected patients were included, 42 cases together with 42 matched controls and 43 unmatched controls. Patients with advanced HIV infection had elevated serum hepcidin and ferritin levels. Hepcidin levels correlated inversely with CD4 cells and hemoglobin. Cases had significantly higher hepcidin and ferritin concentrations at cohort enrollment compared to matched controls, but these differences were fully accounted for by the cases who started TB treatment between day 31 and 60 after enrollment. Hepcidin levels were not different in those with or without hepatitis C infection.

Conclusion: Iron metabolism is distorted in advanced HIV infection with CD4 cell counts correlating inversely with serum hepcidin levels. High serum hepcidin levels and hyperferritinemia were found in patients starting TB treatment shortly after cohort enrollment, suggesting that these parameters have a predictive value for development of manifest TB in HIV-infected patients.

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Related in: MedlinePlus

Correlation of serum hepcidin levels with hematology and iron parameters.Spearman correlation coefficient of serum hepcidin levels with (A) CD4 cell count, (B) serum ferritin levels, (C) hemoglobin levels and (D) mean corpuscular volume (MCV).
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pone-0079904-g001: Correlation of serum hepcidin levels with hematology and iron parameters.Spearman correlation coefficient of serum hepcidin levels with (A) CD4 cell count, (B) serum ferritin levels, (C) hemoglobin levels and (D) mean corpuscular volume (MCV).

Mentions: Median serum hepcidin levels in the whole group of HIV-infected patients were above reference values for healthy Dutch adult males (7.3 vs. 4.5 nM; p<0.001) and premenopausal females (3.1 vs. 2.0 nM; p = 0.028) [16], [22]. However, these higher hepcidin were largely restricted to cases and matched controls, i.e. those with advanced HIV infection (table 2). The unmatched male controls had a similar median hepcidin level value as healthy Dutch adults (4.4 [2.1–8.1] nM), but female unmatched controls had a higher median hepcidin level (4.4 [1.5–8.2] nM). The higher hepcidin levels in cases compared to unmatched controls were associated with higher serum levels of the iron storage protein ferritin and lower serum iron, TIBC and mean corpuscular volume (MCV) values (table 2). Serum hepcidin levels also correlated inversely with CD4 cell counts, hemoglobin levels and MCV, and positively with serum ferritin levels (Fig. 1A–D).


Inverse relationship of serum hepcidin levels with CD4 cell counts in HIV-infected patients selected from an Indonesian prospective cohort study.

Wisaksana R, de Mast Q, Alisjahbana B, Jusuf H, Sudjana P, Indrati AR, Sumantri R, Swinkels D, van Crevel R, van der Ven A - PLoS ONE (2013)

Correlation of serum hepcidin levels with hematology and iron parameters.Spearman correlation coefficient of serum hepcidin levels with (A) CD4 cell count, (B) serum ferritin levels, (C) hemoglobin levels and (D) mean corpuscular volume (MCV).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3823592&req=5

pone-0079904-g001: Correlation of serum hepcidin levels with hematology and iron parameters.Spearman correlation coefficient of serum hepcidin levels with (A) CD4 cell count, (B) serum ferritin levels, (C) hemoglobin levels and (D) mean corpuscular volume (MCV).
Mentions: Median serum hepcidin levels in the whole group of HIV-infected patients were above reference values for healthy Dutch adult males (7.3 vs. 4.5 nM; p<0.001) and premenopausal females (3.1 vs. 2.0 nM; p = 0.028) [16], [22]. However, these higher hepcidin were largely restricted to cases and matched controls, i.e. those with advanced HIV infection (table 2). The unmatched male controls had a similar median hepcidin level value as healthy Dutch adults (4.4 [2.1–8.1] nM), but female unmatched controls had a higher median hepcidin level (4.4 [1.5–8.2] nM). The higher hepcidin levels in cases compared to unmatched controls were associated with higher serum levels of the iron storage protein ferritin and lower serum iron, TIBC and mean corpuscular volume (MCV) values (table 2). Serum hepcidin levels also correlated inversely with CD4 cell counts, hemoglobin levels and MCV, and positively with serum ferritin levels (Fig. 1A–D).

Bottom Line: Iron parameters including hepcidin were compared using samples collected at cohort enrollment, and compared with recently published reference values for serum hepcidin.Cases had significantly higher hepcidin and ferritin concentrations at cohort enrollment compared to matched controls, but these differences were fully accounted for by the cases who started TB treatment between day 31 and 60 after enrollment.High serum hepcidin levels and hyperferritinemia were found in patients starting TB treatment shortly after cohort enrollment, suggesting that these parameters have a predictive value for development of manifest TB in HIV-infected patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine Faculty of Medicine, Padjadjaran University/Hasan Sadikin Hospital, Bandung, Indonesia ; Health Research Unit, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia.

ABSTRACT

Background: Distortion of iron homeostasis may contribute to the pathogenesis of human immunodeficiency virus (HIV) infection and tuberculosis (TB). We studied the association of the central iron-regulatory hormone hepcidin with the severity of HIV and the association between hepcidin and other markers of iron homeostasis with development of TB.

Methods: Three groups of patients were selected from a prospective cohort of HIV-infected subjects in Bandung, Indonesia. The first group consisted of HIV-infected patients who started TB treatment more than 30 days after cohort enrollment (cases). The second group consisted of HIV-infected patients who were matched for age, gender and CD4 cell count to the cases group (matched controls). The third group consisted of HIV-infected patients with CD4 cell counts above 200 cells/mm(3) (unmatched controls). Iron parameters including hepcidin were compared using samples collected at cohort enrollment, and compared with recently published reference values for serum hepcidin.

Results: A total of 127 HIV-infected patients were included, 42 cases together with 42 matched controls and 43 unmatched controls. Patients with advanced HIV infection had elevated serum hepcidin and ferritin levels. Hepcidin levels correlated inversely with CD4 cells and hemoglobin. Cases had significantly higher hepcidin and ferritin concentrations at cohort enrollment compared to matched controls, but these differences were fully accounted for by the cases who started TB treatment between day 31 and 60 after enrollment. Hepcidin levels were not different in those with or without hepatitis C infection.

Conclusion: Iron metabolism is distorted in advanced HIV infection with CD4 cell counts correlating inversely with serum hepcidin levels. High serum hepcidin levels and hyperferritinemia were found in patients starting TB treatment shortly after cohort enrollment, suggesting that these parameters have a predictive value for development of manifest TB in HIV-infected patients.

Show MeSH
Related in: MedlinePlus