Non-transferrin-bound iron and hepatic dysfunction in African dietary iron overload.
BACKGROUND
Circulating iron is normally bound to transferrin. Non-transferrin-bound iron (NTBI) has been described in most forms of iron overload, but has not been studied in African dietary iron overload. This abnormal iron fraction is probably toxic, but this has not been demonstrated.


METHODS
High-pressure liquid chromatography was used to assay serum NTBI in 25 black African subjects with iron overload documented by liver biopsy and in 170 relatives and neighbours. Levels of NTBI were correlated with indirect measures of iron status and conventional liver function tests.


RESULTS
Non-transferrin-bound iron (> 2 micromol/L) was present in 43 people, 22 of patients of whom underwent liver biopsy and 21 relatives and neighbours. All but four of these had evidence of iron overload on the basis of either liver biopsy or elevated transferrin and serum ferritin concentrations. Among all 195 subjects, the presence of NTBI in serum was independently related to elevations in alanine and aspartate aminotransferase activity and bilirubin concentration. This relationship between serum NTBI and hepatic dysfunction was confirmed in the subgroup of 25 subjects with iron overload documented by liver biopsy. Non-transferrin-bound iron correlated significantly with elevations in alanine and aspartate aminotransferase activities after adjustment for hepatic iron grades, inflammation and diet.


CONCLUSIONS
Non-transferrin-bound iron was found to be commonly present in African patients with dietary iron overload and to correlate with transferrin saturation and serum ferritin concentration. The independent relationship between NTBI and elevated liver function tests suggests that it may be part of a pathway leading to hepatic injury.
Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
L
L
McNamara
A P
AP
MacPhail
E
E
Mandishona
P
P
Bloom
A C
AC
Paterson
T A
TA
Rouault
V R
VR
Gordeuk
D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D002352:Carrier Proteins / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005293:Ferritins / Q000097:blood; D006801:Humans; D007501:Iron / Q000097:blood*; D019190:Iron Overload / Q000097:blood / Q000209:etiology*; D019266:Iron, Dietary / Q000009:adverse effects*; D033862:Iron-Binding Proteins; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000378:metabolism; D013019:South Africa; D014168:Transferrin / Q000378:metabolism*; D033863:Transferrin-Binding Proteins
D002352:Carrier Proteins; D019266:Iron, Dietary; D033862:Iron-Binding Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D033863:Transferrin-Binding Proteins; D005293:Ferritins; D007501:Iron; D001219:Aspartate Aminotransferases