Measurements of iron status and survival in African iron overload.

INTRODUCTION: Dietary iron overload is common in southern Africa and there is a misconception that the condition is benign. Early descriptions of the condition relied on autopsy studies, and the use of indirect measurements of iron status to diagnose this form of iron overload has not been clarified. METHODS: The study involved 22 black subjects found to have iron overload on liver biopsy. Fourteen subjects presented to hospital with liver disease and were found to have iron overload on percutaneous liver biopsy. Eight subjects, drawn from a family study, underwent liver biopsy because of elevated serum ferritin concentrations suggestive of iron overload. Indirect measurements of iron status (transferrin saturation, serum ferritin) were performed on all subjects. Histological iron grade and hepatic iron concentration were used as direct measures of iron status. RESULTS: There were no significant differences in either direct or indirect measurements of iron status between the two groups. In 75% of these subjects the hepatic iron concentration was greater than 350 micrograms/g dry weight, an extreme elevation associated with a high risk of fibrosis and cirrhosis. Serum ferritin was elevated in all subjects and the transferrin saturation was greater than 60% in 93% of the subjects. Hepatomegaly was present in 20 of the 22 cases and there was only a moderate derangement in liver enzymes except for a tenfold increase in the median gamma-glutamyl transpeptidase concentration. There was a strong correlation between serum ferritin and hepatic iron concentrations (r = 0.71, P = 0.006). After a median follow-up of 19 months, 6 (26%) of the subjects had died. The risk of mortality correlated significantly with both the hepatic iron concentration and the serum ferritin concentration. CONCLUSIONS: Indirect measurements of iron status (serum ferritin concentration and transferrin saturation) are useful in the diagnosis of African dietary iron overload. When dietary iron overload becomes symptomatic it has a high mortality. Measures to prevent and treat this condition are needed.

A traditional beverage prevents iron deficiency in African women of child bearing age.

OBJECTIVE: To determine if a traditional item in the diet might be useful in preventing iron deficiency in African women of child-bearing age. DESIGN: In a prospective study, the iron status of women who did and did not drink traditional beer high in iron and folic acid, was compared. Iron status was determined by a combination of haemoglobin, serum ferritin and transferrin saturation. SETTING: The study was conducted amongst rural villagers in the Murehwa and Zaka districts of Zimbabwe and in Mpumalanga Province, South Africa. SUBJECTS: 112 women aged between 12 and 50 y from a population of 425 rural people participating in on-going family genetic studies. RESULTS: Women who consumed traditional beer had significantly higher serum ferritin concentrations and transferrin saturations compared to non-drinkers (P = 0.0001 and 0.03 respectively). Iron deficiency anaemia was not present in drinkers but the prevalence in non-drinkers was 13%. Forty seven percent of the non-drinkers and only 14% of the drinkers had evidence of iron deficiency (P = 0.002). Six (21%) of the drinkers and none of the non-drinkers had evidence of iron overload (transferrin saturation > 55% and serum ferritin > 400 ug/l). CONCLUSION: We conclude that the consumption of traditional beer, rich in iron, protects women against iron deficiency. While the use of an alcoholic beverage is not ideal, our findings suggest that indigenous cultural practices might be successfully employed or adapted for promoting iron nutrition.

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.

Dietary iron overload as a risk factor for hepatocellular carcinoma in Black Africans.

Although the iron-loading disease, hereditary hemochromatosis, has a strong causal association with hepatocellular carcinoma (HCC), the carcinogenic potential of dietary iron overload in Black Africans is not known. We investigated this potential by evaluating iron status, alcohol consumption, markers for hepatitis B (HBV) and C virus (HCV) infections, and exposure to dietary aflatoxin B1 in 24 rural patients with this tumor, 48 race-, sex-, and age-matched hospital-based controls, and 75 related or unrelated close family members of the cancer patients. Iron overload was defined as a raised serum ferritin concentration in combination with a transferrin saturation > or = 60%, and was confirmed histologically when possible. Among 24 patients and 48 hospital controls, the risk of developing HCC in the iron-loaded subjects was 10.6 (95% confidence limits of 1.5 and 76.8) relative to individuals with normal iron status, after adjusting for alcohol consumption, chronic HBV and HBC infections, and exposure to aflatoxin B1. The risk of HCC in subjects with HBV infection was 33.2 (7.2, 153.4) (odds ratio [95% confidence limits]), HCV infection 6.4 (0.3, 133.5), and alcohol consumption 2.0 (0.5, 8.2). Aflatoxin B1 exposure did not appear to increase the risk of HCC. The population attributable risk of iron overload in the development of HCC was estimated to be 29%. Among 20 cancer patients and 75 family members, the risk of developing HCC with iron overload was 4.1 (0.5, 32.2). We conclude that dietary iron overload may contribute to the development of HCC in Black Africans.

Evidence of genetic transmission in African iron overload.

Iron overload in Africa was previously regarded as purely due to excessive iron in traditional beer, but we recently found evidence that transferrin saturation and unsaturated iron binding capacity may be influenced by an interaction between dietary iron content and a gene distinct from any HLA-linked locus. To determine if serum ferritin follows a genetic pattern and to confirm our previous observations, we studied an additional 351 Zimbabweans and South Africans from 45 families ranging in size from two to 54 members. Iron status was characterized with repeated morning measurements of serum ferritin, transferrin saturation, and unsaturated iron binding capacity after supplementation with vitamin C. For each measure of iron status, segregation analysis was consistent with an interaction between a postulated iron-loading gene and dietary iron content (P < .01). In the most likely model, transferrin saturation is 75% and serum ferritin is 985 micrograms/L in a 40-year-old male heterozygote with an estimated beer consumption of 10,000 L, whereas the saturation is 36% and serum ferritin is 233 micrograms/L in an unaffected individual with identical age, sex, and beer consumption. This segregation analysis provides further evidence for a genetic influence on iron overload in Africans.