Higher Liver Iron Concentration Research Articles

Iron overload in bone marrow transplant recipients.

We examined the degree of hepatic iron overload in patients receiving marrow transplant for hematologic malignancy and evaluated a new method of morphometric analysis of marrow iron content as a means of estimating hepatic iron stores in these patients. The iron content of marrow and liver specimens from 10 consecutive patients who died between 50 and 100 days after transplant was determined by spectrophotometry. Their mean age was 34.9 years (range 10-59). The mean time to death from disease onset was 2.2 years (0.5-8.7). Patients had received 30.2 +/- 17.4 units of red cells during the transplant period and 47.6 +/- 25.9 red cell units from diagnosis to death. The median hepatic iron concentration (HIC) was 4307 microg/g dry weight (range 1832-13120; normal 530-900) and the median hepatic iron index (HIC (micromol/g dry weight/age (years)) was 3.85 (0.76-8.14). The median biochemical marrow iron content was 1999 microg/g dry weight (range 932-3942). Morphometric analysis of the marrow iron content was performed on digital photomicrographs of a single Prussian blue-stained section of marrow. Strong correlations were demonstrated between morphometric marrow iron content and (1) biochemical marrow iron content (r = 0.8, P= 0.006) and (2) biochemical hepatic iron index (r = 0.82, P = 0.004). We conclude that marrow transplant recipients have a high liver iron content at 50-100 days post transplant with the hepatic iron index in the hereditary hemochromatosis range. Computerized morphometric marrow iron determination is a readily available means of estimating hepatic iron stores in these patients.

Liver iron concentrations in sudden infant death syndrome.

To determine the biological significance of high concentrations of non-haem iron in the livers of infants dying from sudden infant death syndrome (SIDS), liver samples were obtained at necropsy from 66 infants who died from SIDS and 28 control infants who died before 2.5 years of age. All were full term deliveries. Liver iron concentrations decreased rapidly with age in the two groups. Liver iron concentrations in the SIDS infants and controls were compared for those infants who died between 1 month and 1 year of age. The median liver iron concentration in the SIDS infants was 296 micrograms/g wet weight; significantly higher than the median of 105 micrograms/g in controls. There was an inverse relation between iron concentration and age in the two groups, but an analysis of covariance confirmed the significantly lower values in controls. The frequency (22%) of HLA-A3 in SIDS infants was similar to that expected for the United Kingdom population (25%) and does not implicate the gene for haemochromatosis as a cause of high liver iron concentrations. These findings show that the peak incidence of SIDS occurs when mean concentrations of iron in liver tissue are higher than at any other time of life. Although a primary causal connection seems unlikely, high tissue iron concentrations may lower resistance to infection and enhance free radical formation, leading to tissue damage.

Hepatic iron in dialysed patients given intravenous iron dextran.

Five percutaneous biopsy and 17 necropsy liver specimens were analysed histologically and chemically for iron content in 22 patients receiving dialysis for chronic renal failure, 13 of whom were given intravenous iron-dextran. Brissot scores for assessing histological hepatic iron deposition and chemically measured liver iron concentrations correlated closely. Both variables depended on total cumulative dose of iron, and to a lesser extent, on time since the last dose. Fibrosis (seen in five patients) was minimal and non-specific. Electron microscopic examination showed that there was no generalised damage and confirmed the presence of iron in the hepatocytes in the form of ferritin. High liver iron concentrations, in excess of 1000 micrograms/100 mg dry weight, were seen in two patients. Four others given comparable cumulated amounts (18-23 g iron) did not have such high concentrations. Plasma ferritin concentrations were high in eight patients, some with and some without fibrosis. The risk of temporarily high iron deposition in the liver causing damage seemed to be minimal when weighed against the benefit of increased haemoglobin in most of the patients. Intravenous iron treatment merits further evaluation, particularly with the advent of erythropoietin treatment, which requires continuously available iron.

Hepatic lipid peroxidation in vivo in rats with chronic iron overload.

Peroxidative decomposition of cellular membrane lipids is a postulated mechanism of hepatocellular injury in parenchymal iron overload. In the present study, we looked for direct evidence of lipid peroxidation in vivo (as measured by lipid-conjugated diene formation in hepatic organelle membranes) from rats with experimental chronic iron overload. Both parenteral ferric nitrilotriacetate (FeNTA) administration and dietary supplementation with carbonyl iron were used to produce chronic iron overload. Biochemical and histologic evaluation of liver tissue confirmed moderate increases in hepatic storage iron. FeNTA administration produced excessive iron deposition throughout the hepatic lobule in both hepatocytes and Kupffer cells, whereas dietary carbonyl iron supplementation produced greater hepatic iron overload in a periportal distribution with iron deposition predominantly in hepatocytes. Evidence for mitochondrial lipid peroxidation in vivo was demonstrated at all three mean hepatic iron concentrations studied (1,197, 3,231, and 4,216 micrograms Fe/g) in both models of experimental chronic iron overload. In contrast, increased conjugated diene formation was detected in microsomal lipids only at the higher liver iron concentration (4,161 micrograms Fe/g) achieved by dietary carbonyl iron supplementation. When iron as either FeNTA or ferritin was added in vitro to normal liver homogenates before lipid extraction, no conjugated diene formation was observed. We conclude that the presence of conjugated dienes in the subcellular fractions of rat liver provide direct evidence of iron-induced hepatic mitochondrial and microsomal lipid peroxidation in vivo in two models of experimental chronic iron overload.