African Iron Overload and hepatocellular carcinoma (HA‐7–0–080)

Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.

African Iron Overload and hepatocellular carcinoma ha 7 0 080

Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.

The Effect of the Host’s Iron Status on Tuberculosis

Several lines of evidence have suggested that Iron is critical for Mycobacterium tuberculosis growth in macrophages. Macrophage Iron loading in patients with African Iron Overload increases the risk of tuberculosis (TB) and may worsen TB outcome. Likewise, macrophage Iron loading may contribute to an increased predisposition toward TB in HIV infection. Human genetic disorders or variations may increase the risk of TB or worsen its outcome through macrophage Iron loading, including the haptoglobin 2-2 phenotype, NRAMP1 polymorphisms (at least in Africans and Asians), and possibly ferroportin 1 mutations, but not HFE hemochromatosis. Thus, the host’s Iron status may be an important yet underevaluated factor in TB prevention and therapy and in TB vaccine design.

African Iron Overload and hepatocellular carcinoma (HA‐7–0–080)

Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.

African Iron Overload and hepatocellular carcinoma ha 7 0 080

Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.

Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of Iron Overload.

To identify a new marker of expression of disease, independent of HFE genotype in patients with hereditary haemochromatosis (HHC), the total peripheral blood lymphocyte counts were analysed according to Iron status in two groups of subjects with HFE mutations. The groups consisted of 38 homozygotes for C282Y, and 107 heterozygotes for the C282Y or compound heterozygotes for C282Y and H63D. For control purposes, total lymphocyte counts and Iron status were also examined in 20 index patients with African dietary Iron Overload, a condition not associated with HFE mutations, and in 144 members of their families and communities. Mean lymphocyte numbers were lower in C282Y homozygous HHC index subjects with cirrhosis and higher Iron stores than in those without cirrhosis and with lower Iron burdens [(1.65 +/- 0.43) x 10(6)/mL vs. (2.27 +/- 0.49) x 10(6)/mL; p = 0.008]. Similarly, mean lymphocyte counts were significantly lower in C282Y heterozygotes and C282Y/H63D compound heterozygotes with Iron Overload and increased serum ferritin concentrations compared to those with normal serum ferritin concentrations (p < 0.05). Statistically significant negative correlations were found, in males, between lymphocyte counts and the total body Iron stores, either in C282Y homozygous HHC patients (p = 0.031 in a multiple regression model dependent on age) and in C282Y heterozygotes or C282Y/H63D compound heterozygotes with Iron Overload (p = 0.029 in a simple linear model). In contrast, lymphocyte counts increased with increasing serum ferritin concentrations among the index subjects with African Iron Overload (r = 0.324, not statistically significant) and among the members of their families and communities (r = 0.170, p = 0.042). These results suggest that a lower peripheral blood lymphocyte count is associated with a greater degree of Iron loading in HFE haemochromatosis but not in African Iron Overload, and they support the notion that the lymphocyte count may serve as a marker of a non-HFE gene that influences the clinical expression of HFE haemochromatosis.

African Iron Overload and hepatocellular carcinoma (HA‐7–0–080)

Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.

African Iron Overload and hepatocellular carcinoma ha 7 0 080

Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, Iron Overload in Africa is not thought to be etiologically related to this malignancy. To determine if African Iron Overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular Iron. Subjects were stratified according to hepatocellular Iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with Iron Overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between Iron Overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with Iron Overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without Iron Overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that Iron Overload may be a risk factor for hepatocellular carcinoma in Africa.

Transferrin Polymorphism Influences Iron Status in Blacks

Background: Genetic variants of human transferrin (TF) have been described, but little is known about their functional differences. We studied Iron status according to TF phenotype in a healthy Zimbabwean population and in subjects at risk of African Iron Overload.

Methods: The study population consisted of 483 nondrinkers, 31 drinking spouse pairs, and 5 family pedigrees (n = 88) with index cases of Iron Overload. TF phenotypes were determined using starch gel electrophoresis. To evaluate Iron status, serum Iron, total Iron-binding capacity (TIBC), ferritin, and soluble TF receptors were measured, and the percentage of saturation and the serum Iron:TF ratio were calculated. The binding of the TF variants was studied by equilibrium dialysis.

Results: The reference population was characterized by a high TF D allele frequency (0.050) and a complete absence of homozygous TF DD individuals. Similar allele frequencies were observed in subjects at risk of African Iron Overload. In the reference population, male TF CD heterozygotes had significantly lower ( P