Trasplante cardíaco por hemocromatosis. Caso pediátrico / Cardiac transplantation due to hemochromatosis. A pediatric case report

La hemocromatosis es una enfermedad caracterizada por el excesivo depósito de hierro en múltiples órganos, entre ellos hígado, páncreas, piel y corazón. La infiltración de este último es un importante factor en morbilidad y mortalidad. Presentamos un caso de un paciente pediátrico con insuficiencia cardíaca terminal que ameritó trasplante cardíaco, que resultó sin complicaciones. Posterior a la cirugía, mostró mejoría bioquímica y clínica, lo que influyó positivamente en su calidad de vida y prolongó su supervivencia.

Hemochromatosis is a disease characterized by excess iron stores in multiple organs, including the liver, pancreas, skin, and heart. The infiltration of the heart is an important factor in morbidity and mortality. Here we describe the case of a pediatric patient with end-stage heart failure who required a heart transplantation, with no complications. After the surgery, she showed biochemical and clinical improvement, with a positive impact on her quality of life and a prolonged survival.

Naringin is a promising natural compound for therapy of iron-overload disorders

Abstract Naringin has been shown to exhibit satisfying iron chelation capacity. Considering the side effects of routinely-used iron chelator (desferrioxamine, DFO), we decided to evaluate the iron chelation potency of naringin to discover whether or not it can be a promising natural substitute for treatment of excessive iron-related diseases. 35 mice were classified into five groups of 7 and subjected to iron dextran administration to induce the iron-overload condition. Iron-overloaded mice were then treated with normal saline (as control), naringin or DFO Morphology changes, and iron deposition in liver tissues were studied using H&E and Perl's staining. The results revealed that naringin is more potent than DFO in removing excessive iron ions deposited in liver tissues, indicating that naringin is a promising natural compound for therapy of iron overload disorders

Sobrecarga de hierro: complicación frecuente del trasplante de progenitores hematopoyéticos / Iron Overload: frequent complication ofhematopoietic stem cell transplantation

La sobrecarga de hierro es común en pacientes receptores de trasplante de progenitores hematopoyéticos. En estos pacientes, la ferritina y la saturación de transferrina, pre- y postrasplante, están aumentadas debido a las frecuentes transfusiones de sangre. Además, la sobrecarga de hierro postrasplante puede relacionarse con otras complicaciones como las infecciones, las mucositis y la enfermedad injerto contra hospedero. Una ferritina elevada antes del trasplante alogénico es un factor de mal pronóstico para la sobrevida y la mortalidad no relacionada. Para el monitoreo y diagnóstico de la sobrecarga de hierro se cuenta con diversa herramientas entre las que la ferritina continúa siendo una de las más utilizadas(AU)

Iron overload is common in hematopietic stem cell transplantation (HSCT) recipients. In these patients, pre- and early post-transplant ferritin and transferrin saturation were found to be highly elevated due to high transfusion requirements. In addition to that, post-HSCT iron overload may be related to other complications such as infections, mucositis, and acute graft-versus-host disease. An elevated ferritin level before allogeneic HSCT is an adverse prognostic factor for overall and nonrelapse mortality. There are several diagnostic tools for iron overload but ferritinis still one of the most used(AU)

Anti-oxidative protection against iron overload-induced liver damage in mice by Cajanus cajan (L.) Millsp. leaf extract.

In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload.

Estudio sobre la sobrecarga de hierro en pacientes con hepatitis C crónica / [A study on hepatic iron overload in chronic hepatitis C patients].

BACKGROUND: Hepatitis C is a worldwide chronic liver disease. Different factors have been found to be associated with an increased progression to severe liver fibrosis, such as alcohol intake higher than 30 g/day, older age at infection and co-infection. Nevertheless, different research centers have found conflicting data concerning the liver iron overload fibrogenic role. AIM: To assess the association between hepatic iron overload and fibrosis stage grades in hepatitis C Virus carriers, hepatic steatosis and demographic variables. METHODS: In this descriptive study we recruited 290 positive anti-HCV and qualitative HCV-RNA, treatment naive chronic hepatitis C outpatients registered fom 2007 to 2009 at the Federal University of Bahia’s Hospital. The variables studied in the liver biopsy results were: 1) fibrosis stage according to META VIR score (F0-F4), 2) iron overload presence or absence according to Perls staining, and 3) presence or absence of steatosis. Fibrosis stages were categorized as mild/moderate (F0-F2) and severe (F3-F4). Exclusion criteria were hepatitis B virus and human immunodeficiency virus co-infection, and primary or secondary hemochromatosis. The statistical analysis was performed using Chi-square and Student’s t tests, with the ssoftware: SPSS 17. A P value < 0.05 was considered as significant. RESULTS: Severe fibrosis was statistically associated with older age, iron overload presence (P = 0.003) and steatosis (P = 0.01). CONCLUSIONS: In this study hepatic iron overload and hepatic steatosis were associated with severe hepatic fibrosis (METAVIR F3-F4).

Major causes of hospital admission in beta thalassemia major patients in southern Iran

Beta thalassemia major is a prevalent hereditary disease in Mediterranean region especially Iran. Early blood transfusion is necessary for most of the patients and frequent transfusion can cause various medical problems for the patients. The aim of this study was to find major causes of hospital admission in beta thalassemia major patients to reach the accurate preventive and therapeutic plans for these patients. Four hundred twenty six patients were admitted to the Nemazee Hospital [the main University referral Hospital Center affiliated to Shiraz University of Medical Sciences in Pars Province, southern Iran] during 3 years period [January 2007 to January 2010]. A questionnaire was filled containing age, gender, hemoglobin level, frequency of blood transfusions, deferoxamine injection, cause of hospital admission and hospital course. The mean age of patients was 11.28 years. The mean serum ferritin level was 1820 +/- 749 Hg/lit. Two hundred fifty five [59.75%] patients were male and 171 [40.25%] patients were female. The top five most prevalent causes of hospital admission were splenectomy [21.8%], infections [19.9%], congestive heart failure [19.0%], diabetes mellitus [13.4%], and Liver biopsy [11.5%]. [P=0.0002]. Results of this study revealed that infections and complications due to iron overload are major causes of hospital admission in beta thalassemia major patients

Indicators of renal glomerular and tubular functions in patients with beta-thalassaemia major

There are limited data concerning the assessment of renal function in beta-thalassaemia major, with no study of such involvement in Omani patients. The objective of this study was to establish the pattern of renal glomerular and tubular function using traditional and specific laboratory tests in patients with beta-thalassaemia major. This cross-sectional study, from January-July 2008, included 30 patients of the Thalassaemia Clinic at the Royal Hospital, Oman, with transfusion-dependent homozygous beta-thalassaemia major. They included 15 males and 15 females, aged 16-32 years with mean +/- standard deviation of 21.23 +/- 3.42 years. The medical records were reviewed and renal function states assessed as follows: serum creatinine, estimated glomerular filtration rate [eGFR]; urea; phosphate, fractional excretion of filtered sodium [FENa]; urine albumin: creatinine index; urine beta2-microglobulin:creatinine index; tubular reabsorption of phosphate [TRP], and tubular maximum phosphate reabsorption [TmP]/GFR. All patients had eGFR >90 ml/min/1.73m2; serum creatinine <90 micro mol/L; serum urea <6.0 mmol/L, and urine albumin: creatinine <2.5 mg/mmol. Only 2 [6.7%] patients had FENa >1% and 3 [10.0%] patients had urine s2-microglobulin: creatinine >22 micro g/mmol. All patients had TRP >0.85, of whom seven [23.3%] patients had values within the range of 0.85-0.95 and 23 [76.7%] had values >0.95. Also, all patients had TmP/GFR >1.0 mmol/L, of whom only one [3.3%] patient had TmP/GFR of 1.0-1.5, and 29 [96.7%] patients had TmP/GFR >1.5 mmol/L. Finally, 24 [80%] patients had serum phosphate >1.4 mmol/L. Linear regression revealed a highly significant correlation between serum phosphate and TmP/GFR [r = 0.904, P < 0.001]. Renal function, glomerular and tubular, appears to be well preserved in beta-thalassaemia major. Almost all renal function indicators were within the recommended ranges. Raised TmP/GFR and TRP were noted in the majority of patients, reflecting an up-trend in serum phosphate and therefore increasing renal phosphate reabsorption

L-Carnitine ameliorates the iron mediated DNA degradation in peripheral leukocytes of beta-thalassemic children

Iron overload is a common complication in beta-thalassemia that induces intracellular oxidative stress producing lesions in the DNA including double strand breaks. The aim of this study was to evaluate DNA damage in peripheral leukocytes of-thalassemic children and to investigate its association with the iron overload and the role of L-carnitine therapy upon this damage. Fifty beta-thalassemic children [25 TM and 25 TI] with 20 age and sex matched apparently healthy children [control group] were included. Serum ferritin level was measured by ELISA. DNA damage was evaluated by the Gel electrophoresis to determine the total DNA genomic damage [TGD]. The intensity of DNA nucleoprotein was measured by software Gel Pro analyzer computer program as maximum optical density [max.OD] values of apoptotic fragments of DNA at 200bp, 400bp and 600bp. The smear shape pattern on gel electrophoresis and Pro-Gel analyzer chart indicating double strand breakage of the DNA was detected in 76% of the thalassemic children. The thlassemic patients [the whole group and each of TM and TI groups] had significantly higher prevalence of DNA double-strand breaks in their leukocytes with significant higher values of max. OD at 200,400and 600 bp compared to the control group. The thalassemic children on regular L-carnitine therapy [50 mg/kg/d for at least 6 months] had significantly lower prevalence and degrees of DNA breaks [TGD] with significant lower max. OD values at 200,400 and 600 bp compared to those not on L-carnitin therapy. There was significant positive correlation between the mean serum ferritin levels and the values of max. OD at 200 and 400bp. The data obtained from the Roe Curve shows that, the best sensitivity of 95% and specificity of 75% for the mean serum ferritin were at the cut off point of 820 ng/ml to predict the ocurrence of TGD in thalassemic leukocytes. Thalassemic children had significant DNA double-strand breaks in their leukocytes that was positively correlated to their iron overload reflected by serum ferritin level and can be ameliorated by L-carnitine supplementation

[Importance of OGTT for diagnosis of diabetes in thalassemia major patients]

Thalassemia major is a genetic disorder. Blood transfusion is critical for survival in these patients. Over the course of the past two and three decade's hyper transfusion therapy in these patients has increased significant improvement in life expectancy and quality of life. Unfortunately this type of therapy increased the frequency of complication due to iron overloud. The aim of this study was to evaluate the prevalencey of diabetes, impaired fasting glucose and impaired glucose tolerance in patients with thalassemia major, with 10-27 years of age in Tabriz. This descriptive study was done on 56 patients between 10-27 years of age with thalassemia major. The demographic informaiton theraputic regiment, the age of first trasfussion. The level of blood transfusion, the history and dosage of familial history of diabetes, Fe, TIBC, ferritin levels were assessed and recorded. For each patient glucose tolerance test, blood glucose level are performed. In this study prevalence of diabetes mellitus, impaired fasting glucose and impaired glucose tolerance test were found in 8.9%, 28.6% and 7.1% of patients respectively. This study showed that despite recent therapy with Desferal in the management of beta-thalassemia major, the risk of secondary endocrine dysfunction remains high. Prevalence of diabetes mellitus, impaired fasting glucose and impaired glucose tolerance test are greater than general population. Endocrine evaluation in patients with thalassemia major must be carried out regularly especially in those patients over the age of 10 years

Sobrecarga moderada de ferro em ratos: interação com frutanos e/ou fitato no metabolismo hepático e ósseo / Moderate iron overload in rats: interaction with fructans and/or phytate in hepatic and bone metabolism

O excesso de Fe no organismo gera espécies reativas de oxigênio (ERO) que são potencialmente tóxicas. Entretanto, a magnitude dos efeitos da exposição à moderada sobrecarga de Fe e da sua interação com facilitadores e/ou inibidores da absorção mineral não é conhecida. O objetivo deste trabalho foi avaliar esses efeitos e a sua interação com fruta nos e/ou fitato (facilitadores e inibidores da absorção de Fe, respectivamente) nos índices séricos do estado nutricional em Fe, no perfil dos lipídeos séricos e em parâmetros do metabolismo hepático e ósseo. Para o experimento foram utilizados 34 ratos machos Wistar, pesando inicialmente 49,3 ± 3,9g, alojados individualmente em gaiolas de aço semimetabólicas por 92 dias. Uma dieta AIN-93G (Dieta 1: Grupo Controle) e quatro dietas AIN93G modificadas foram usadas para o estudo, com as seguintes características: Dieta 2: sobrecarga moderada de ferro com 550mgFe/kg de ração (Grupo SBC); Dieta 3: sobrecarga moderada de ferro + 18% de farinha de yacon (Grupo SBC+FY); Dieta 4: sobrecarga moderada de ferro + 0,6% de fitato (Grupo SBC+FIT); Dieta 5: sobrecarga moderada de ferro + 18% de farinha de yacon + 0,6 % de fitato (Grupo SBC+FY+FIT). Os resultados demonstraram que a moderada sobrecarga de Fe ou a sua interação com farinha de yacon e/ou fitato não alterou os índices séricos do estado nutricional em Fe. Ocorreu aumento na atividade sérica da AST apenas no grupo SBC (p=0,055). Nos grupos SBC e SBC+FY houve diminuição na concentração do colesterol sérico (p=0,002) e, apenas no grupo SBC+FY+FIT, diminuição da concentração sérica do VLDL. No fígado, houve aumento significativo (p=0,002) da concentração de Fe não-heme nos grupos IO (+83%) e SBC+FIT (+117%) e, em todos os grupos SBC, na atividade da enzima GPx (p=0,000). A atividade da CAT foi menor (p=0,036) apenas para o grupo SBC+FY+FIT. Em todos os grupos SBC ocorreu significativo aumento nos depósitos de hemossiderina em torno das células de Kupffer (p=0,000). Houve aumento na apoptose em todos os grupos SBC, com os grupos SBC+FY e SBC+FY +FIT apresentando o maior número de corpúsculos apoptóticos/área (+405% e +342%, respectivamente) (p=0,000). Não houve alteração nos parâmetros relacionados ao metabolismo ósseo. No grupo SBC+FY houve significativo aumento na absorção aparente de Ca (p<0,05). Conclusões: A moderada sobrecarga de Fe não alterou os índices séricos do estado nutricional em Fe, mas resultou em alterações no tecido hepático e no perfil dos lipídeos séricos. Com exceção do perfil de lipídeos séricos, no qual apenas o fitato pareceu exercer efeito protetor, nos demais parâmetros avaliados a interação com farinha de yacon rica em fruta nos e/ou fitato reverteu parcial ou totalmente as alterações induzidas pela moderada sobrecarga de Fe

Excess Fe in the organism generates potentially toxic reactive oxygen species (ROS). However, the magnitude of the effects of a moderate Fe overload and its interaction with factors which inhibit or facilitate mineral absorption is not known. The aim of the present work was to evaluate such effects and their interaction with fructans and/or phytate (compounds which facilitate and inhibit Fe absorption, respectively) on serum iron status indices, on the profile of serum lipids and on hepatic and bone metabolism parameters. In the experiment, thirty-four male Wistar rats initially weighing 49,3 ± 3,9g were used. The rats were housed in individual stainless-steel wire-mesh cages for 92 days. An AIN-93G diet (Diet 1: Control Group) and four modified AIN-93G diets were used in the study. The modified diets presented the following formulations: Diet 2: moderate Fe overload with 550mgFe/kg diet (IO Group); Diet 3: moderate Fe overload + 18% yacon flour (IO-YF Group); Diet 4: moderate Fe verload + 0.6% phytate (IO-Phy Group); Diet 5: moderate Fe overload + 18% yacon flour + 0.6% phytate (IO-YF-Phy Group). The results demonstrated that a moderate Fe overload or its interaction with yacon flour and/or phytate did not alter the serum iron status indices. An increase in the serum AST activity was observed only in the IO group (p=0,055). In the IO and IO-YF groups, there was a reduction in the serum cholesterol concentration (p=0,002) and a reduction in the serum VLDL concentration was observed only in the IO-YF-Phy group. In the liver, there was a significant increase (p=0,002) in non-heme Fe concentration in the IO (+83%) and IO-Phy (+117%) groups. Also, GPx activity was significantly increased (p=0,000) in all IO groups. CAT activity was lower (p=0,036) only in the IO-YF-Phy group. A significant increase in hemosiderin deposition around Kupffer cells was observed in all IO groups (p=0,000). Apoptosis was increased in all IO groups, whereas the IO-YF and IO-YF-Phy groups showed the largest number of apoptotic bodies/area (+405% and +342%, respectively) (p=0,000). There was no alteration in the parameters related to bone metabolism. In the IO-YF group, there was a significant increase in Ca apparent absorption (p<0,05).Conclusions: The moderate Fe overload did not alter the serum iron status índices, but led to alterations in the hepatic tissue and in the profile of serum lipids. Except for the profile of serum lipids where only phytate seemed to have a protective effect, in the other evaluated parameters the interaction with yacon flour rich in fructans and/or phytate partially or totally reversed the alterations induced by the moderate Fe overload

Cardiovascular complications of thalassemia major and thalassemia intermedia

Cardiac complications due to Iron overload are the most common cause of death in beta-thalassemic patients. Although regular blood transfusions in thalassemia major [TM] patients have improved the quality of life of the patients but the most important complication of such transfusions is iron overload in cardiac tissues. In spite of iron overload in untransfused thalassemia intermedia [TI] patients, the intestinal absorption of iron increases in these patients because of ineffective erythropoesis. The aim of this study was to evaluate cardiac status in thalassemia major and intermedia patients and the investigation of the possible effect of iron overload in the heart of beta-thalassemic patients. 46 patients entered into this study. 26 patients had thalassemia major with regular blood and also chelator transfusions and 20 patients with thalassemia intermedia who had not received regular transfusions. The age of the patients in the 2 groups were similar. The results of clinical evaluation and echocardiographies of the patients of the 2 groups were compared with each other. Collected data were analyzed by means of Chi square and man whitney U tests. Heart failure occurred in two patients with TM [9.52%] and one patient with TI [4.76%]. Considerable pulmonary hypertension [systolic tricuspid gradient >35mmHg] was only present in 3 patients with TI [14.28%]. But systolic dysfunction of left ventricle [ejection fraction<55% or shortening fraction<35%] occurred in 5 patients with TM [23.8%]. In the patients without apparent heart disease, cardiac dimensions, LV mass, LV shortening and ejection fractions, cardiac output and valvular involvement were significantly more in patients with TI. But the maximum speed of systolic flow out of mitral valve in primary phase was higher significantly in TM patients than TI patients. Regular lifelong transfusion and chelation therapy in TM patients prevents premature heart disease and pulmonary hypertension, but LV dysfunction can occur and lead to heart failure. In contrast in TI patients left ventricular function is normal but pulmonary hypertension occurs which may lead to heart failure. Left ventricular performance is better preserved when chelation treatment is adjusted to maintain the serum ferritin concentration at <1000 nanogram/ml

Proponiendo biomarcadores para evaluar las alteraciones en la homeostasis cerebral de hierro y su relación con la fisiopatología de la Enfermedad de Alzheimer / Proposing biomarkers to evaluate the alterations in the brain iron homeostasis and their relation with the physiopathology of Alzheimer's disease

En la fisiopatología de la enfermedad de Alzheimer es conocido que el péptido amiloide- beta produce daño neuronal a través del estrés oxidativo. El desarrollo de este último podría también ser favorecido por un exceso de hierro en el cerebro, observado en algunos pacientes afectados, estado al que es posible llegar por la alteración en la funcionalidad de las múltiples proteínas encargadas de la internalización y depósito del metal en el cerebro. Actualmente las proteínas melanotrasnferrina, lactotransferrina, y neuromelanina se han encontrado alteradas en forma específica en la enfermedad. De las otras proteínas involucradas no existe evidencia, sin embargo, por su función se sugiere ampliamente que también podrían estar implicadas. Además lactotransferrina, ceruloplasmina, neuromelanina y hemo oxigenasa poseen actividades en el metabolismo oxidativo, cuya desregulación podría coadyuvar al desarrollo de la patología. En este trabajo se revisan los conceptos de estrés oxidativo, hierro y proteínas encargadas de la homeostasis cerebral de hierro en relación a la fisiopatología de la enfermedad de Alzheimer.

Multiple lines of evidence have implicated oxidative stress and free radical damage to the pathogenesis and etiology of Alzheimer`s disease (AD). Amyloid-beta peptide contributes to oxidative damage in AD by inducing lipid peroxidation. In addition, iron might contribute to the increased susceptibility of the brain to iron-induced oxidative damage, due to its ability to catalyze the generation of free radicals in biological systems. There are several points in the iron regulation pathway in which alterations may occur, affecting iron metabolism. Altered expression and altered cellular distribution of melanotransferrin, lactotransferrin, and neuromelanin have been reported in the brain tissue of patients suffering AD. In addition, disruptions in lactotransferrin, ceruloplasmin, neuromelanin, and hemo oxygenase may result in oxidative stress. In conclusion, in AD it appears to be an excessive accumulation of iron in the brain and oxidative damage, suggesting a loss of the homeostatic mechanisms that are responsible for regulating iron in the brain.

Effect transfusional of iron overload on hepatic fibrosis in Egyptian beta-thalassemia major patients

Multitransfused beta-thalassemia patients constitute a population with high prevalence of Hepatitis C virus [HCV] infection, because of transmission of HCV from infected blood donors. Increased hepatic iron is assumed to potentiate progression towards liver fibrosis in chronic HCV infection. The aim of the present work is to evaluate the potentiating effect of marked hepatic iron overload and chronic HCV infection on hepatic fibrosis in Thalassemia patients. Sixty eight patients, previously diagnosed to have homozygous beta-thalassemia and followed up at the Hematology Clinic of the New Children's Hospital of Cairo University [44 hepatitis C positive and 24 hepatitis C negative patients], were selected to participate in this study after signing a written informed consent. Their age ranged between 6 and 27 years with a mean age of 9.7 +/- 2.1 years and compared to a group of 42 non thalassemic chronic HCV patients whose age ranged between 7 and 27 years with a mean age of 10.9 +/- 1.5 years [control group]. Liver Biopsies were done for all patients for estimation of stage of hepatic fibrosis and liver iron content [LIC]. The results were then correlated to liver function tests and serum ferritin. The stage of fibrosis and LIC were significantly higher in beta-thalassemia patients than the non thalassemia HCV patients [p = 0.005, p<0.0001 respectively]. There was no significant difference between the two groups of thalassemia as regards staging of fibrosis. The degree of hepatic fibrosis was significantly correlated to the LIC in hepatitis negative thalassemic group while it was significantly correlated to serum ferritin in thalasemic patients with positive HCV. Hepatic iron overload has a potentiating effect on hepatic fibrogenesis in beta-thalassemia major. The proper use of chelating agents is of great importance in delaying progression of liver disease in these patients

The Prevalence of Peripheral Iron Overload and the Presence of HFE gene (H63D) Mutation among the Korean Patients with Nonalcoholic Fatty Liver Disease / 대한간학회지

BACKGROUNDS/AIMS: There are controversies on the role of iron overload in the mechanism of liver injury in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the prevalence of peripheral iron overload, and to study the presence of HFE mutations (C282Y, H63D, S65C) in a cohort of Korean NAFLD patients. METHODS: 255 patients with NAFLD were included. The patients had been diagnosed as having NAFLD by the criteria of elevated aminotransferase levels, compatible ultrasonographic findings and exclusion of other etiologies. Blood samples were tested for chemistry, iron profile, and mutational analysis for HFE gene (C282Y, H63D, S65C). RESULTS: Of the 255 NAFLD patients, the prevalence of peripheral iron overload was 19.2% according to the cutoff level of transferrin saturation (TS) > 45%, and 3.9% of NAFLD patients were having hyperferritinemia over 400 ng/mL. Hyperferritinemia was significantly associated with elevated serum levels of fasting glucose, AST and TS. We found the presence of H63D mutation, either heterozygote or homozygote, among the NAFLD patients with peripheral iron overload. CONCLUSIONS: The prevalence of peripheral iron overload in the Korean NAFLD patients was not rare, and the presence of H63D mutation among NALFD patients was identified. Further studies on the significance of iron overload or HFE mutation in the pathogenesis of NAFLD are needed.

Effect of iron overload on the severity of liver histologic alterations and on the response to interferon and ribavirin therapy of patients with hepatitis C infection

The objective of the present study was to determine the presence of hepatic iron overload in patients with chronic HCV infection and to correlate it with histologic alterations, HCV genotype and response to therapy. Liver tissue samples from 95 patients with chronic hepatitis C were divided into two groups: group I, presence of iron overload in hepatic tissue (Perls' staining) and group II, no iron overload. Hepatic iron overload was detected in 30 (31.6 percent) of 95 patients. Of the 69 patients tested by genotyping, 49 (71.01 percent) were genotype 1 and 20 (28.99 percent) genotype non-1. Iron overload was detected in 14 (28.6 percent) patients with genotype 1 and in 6 (30 percent) with genotype non-1 (P = 0.906). There was a significant difference in fibrosis stage between groups (P = 0.005). In group I (N = 30), one patient had stage F0/F1 of fibrosis, while in group II (N = 65), 22 (33.8 percent) patients had minimal or no fibrosis. Fibrosis stage F2/F3 was observed in 70 percent of group I patients compared to 46.2 percent of group II. Eighty-five patients were treated with a combination of interferon and ribavirin; 29 of them (34.1 percent) had a sustained virologic response and 8 (27.6 percent) of them had hepatic iron overload. Iron overload was detected in 18 (32.1 percent) of the 56 non-responders (P = 0.73). Hepatic iron overload was frequent among patients with chronic hepatitis C and was associated with a more severe stage of liver fibrosis. There was no association between iron overload and HCV genotype and response to interferon and ribavirin therapy.

Iron status parameters in patients with chronic hepatitis C virus infection

Hepatic iron deposition is common in patients with chronic hepatitis C [HCV] and may play a role in progression of liver disease. Aim of the present study was to determine the prevalence of iron overload and to study the relationship between hepatic iron concentration [HIC] and clinical, biochemical and histological characteristics in chronic HCV-infected patients. Patients presenting with anti-HCV and HCV-RNA were included. Hepatic iron concentration was determined in liver tissue by colormetric assay. The association between HIC and age, gender, transaminases [AST and ALT] levels, iron and serum ferritin, transferrin saturation, HCV-RNA level, grading of inflammatory activity, staging of fibrosis, hepatic steatosis, and stainable iron was analyzed. Statistical analysis included the Mann-Whitney test and a multiple linear regression model. 48 patients [58% male] with a mean age of 44 +/- 10 years were studied. Serum iron, ferritin and transferrin saturation were elevated in 27%, 25% and 12.5% of patients respectively. Stainable iron was detected in few patients [16.6%]. Higher grades of stainable iron [2 and 3] were observed in only 6.25%. The HIC >30mmol/g dry weight] was elevated in three patients [6.2%]. Neither grading nor staging were related to HIC. Higher HIC were observed in male patients [p <0.001], in patients with elevated serum ferritin [p = 0.001] and in patients with stainable iron [grade 1; p =0.001]. Multiple linear regression analysis showed that only stainable iron was independently correlated with HIC [p = 0.003]. Iron overload in chronically HCV-infected patients was uncommon and hepatic iron content seemed not to be related to the liver damage process. In the eventuality of iron overload, histochemical liver iron is a useful marker to estimate HIC

Synthesis and biochemical evaluation of novel aminoheterocyclic steroids as potent inhibitors of iron-induced oxidative stress

The objective of this study was to elucidate the potential role of novel synthesized aminosteroidal heterocyclic compounds 2, 5, 9b or 10c against iron-induced oxidative stress with particular insight on erythrocyte ghosts in male rats. Chronic iron supplementation [3000 mg/kg diet] for six weeks significantly increased plasma iron and ferritin levels. It also produced significant increase in plasma TN F-alpha and NO levels. Lipid metabolism was also affected by excess iron, so that plasma and erythrocyte membrane total cholesterol, triglycerides, phospholipids and total lipids levels were significantly elevated. In consequence, a significant increase in plasma leptin level was detected. Iron overload clearly induces oxidative stress as indicated by the significant increase in both plasma and erythrocyte membrane lipid peroxidation levels. Noteworthy, excess iron not only decreased the mean value of erythrocyte membrane protein but also caused marked alterations in the membrane protein fractions with concomitant inhibition in:erythrocyte membrane ATPases activity. On the other hand, treatment with the aminosteriodal heterocyclic compounds especially compounds 5, 2, or 10c in an oral dose of 5mg/kg B.W/day could ameliorate almost all of the changes in plasma and erythrocyte ghosts components induced by iron overload. The efficacious role of these novel synthesized aminosteriods in preventing iron-induced oxidative stress may be mediated through their iron chelating properties, anti-lipid peroxidation activities and membrane stabilizing actions. The encouraging results obtained in the present study lend credence to substantial investigation to assess the use of these compounds as a potent line of therapy to retard the pathogenesis of iron-overload diseases