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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in 78 Italian patients with hereditary hemochromatosis as well as the relation between HCV antibody (anti-HCV) status, hepatitis B surface antigen (HBsAg) and liver histology. None of the patients had been transfused or ever consumed more than 60 g of alcohol per day. Eighteen showed histological signs of chronic hepatitis, active cirrhosis was present in 12, chronic active hepatitis in 4 and chronic persistent hepatitis in 2. Liver fibrosis or cirrhosis without inflammatory activity was observed in 31 subjects, whereas liver histology was normal except for iron overload in 18. The prevalence of HBsAg in the whole series was 5% and of anti-HCV was 20.5%. The prevalence of HBsAg and anti-HCV was significantly higher in the chronic hepatitis group than in the fibrosis/cirrhosis (p = 0.01) and the normal groups (p < 0.01). Fourteen of 18 hereditary hemochromatosis patients with chronic hepatitis were HBsAg (4) or anti-HCV (10) positive and all the latter subgroup had HCV-RNA in their serum as shown by the polymerase chain reaction. Although most of the patients with associated chronic hepatitis had cirrhosis, their serum ferritin levels and amount of mobilizable iron were significantly lower than those of the fibrosis/cirrhosis group (p < 0.01). This indicates that hepatitis viral infection acts synergistically with iron in accelerating the development of liver damage.
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PMID:Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection. 148 15

Sixteen patients (age range, 3 to 17 years) with transfusion-dependent beta-thalassemia major were studied prospectively, beginning at the onset of chelation therapy with deferoxamine (desferrioxamine). A liver biopsy specimen was obtained from each patient at the start of the study, and periodically thereafter. Liver histologic features, iron content, and iron excretion were assessed during the course of the study. Hepatic iron levels from liver biopsy specimens appeared to correlate well with serum ferritin levels in the younger less heavily iron-loaded patients; however, in patients with higher serum ferritin levels, hepatic iron appeared to reach a saturation level. Fourteen of the 16 patients showed a pattern of marbled fibrosis of the liver in their initial biopsy specimens. Follow-up biopsy specimens from nearly all of the patients showed a substantial reduction in iron concentration, but only two of seven patients showed improvement in the degree of hepatic fibrosis three to five years later. Patients less than 8 years old exhibited a normal pattern of linear growth until approximately the age of 10 years, followed by a progressive decrease to the 30th to 40th percentile. Two patients, aged 18 and 22 years, died of cardiac disease during the study. These findings suggest that chelation therapy in patients with transfusion-dependent thalassemia needs to be initiated at an early age, possibly before 3 years, if significant liver fibrosis and growth impairment are to be effectively prevented.
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PMID:A prospective evaluation of iron chelation therapy in children with severe beta-thalassemia. A six-year study. 334 15

To determine the therapeutic effect of long-term, intensive iron chelation therapy, we studied liver iron content and histology in four children with thalassaemia major during 52-83 months of intensive therapy with desferrioxamine. The initial biopsies obtained prior to or within 21 months after beginning chelation therapy had Grade IV iron staining, with heavy iron deposition present in parenchymal and reticuloendothelial cells. Subsequent biopsies, obtained when serum ferritin levels had fallen to 71-246 micrograms/l, contained Grade 0 or Grade I stainable iron. Little or no iron was present in parenchymal or reticuloendothelial cells. The liver iron concentration, measured by magnetic susceptibility, returned to normal or nearly normal levels. Hepatic fibrosis did not progress during treatment with desferrioxamine. These findings demonstrate that intensive and sustained chelation therapy with desferrioxamine will remove excessive liver iron and preserve hepatocellular structure.
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PMID:Depletion of excessive liver iron stores with desferrioxamine. 647 38

The improvement in survival and quality of life of iron-overloaded patients achieved by regular subcutaneous chelation has been extensively documented over the years. A review of the long-term results allows one to establish the following points: (1) with regular subcutaneous chelation, a negative iron balance can be obtained in most patients, except very young ones; (2) severe deferoxamine (DFO) toxicity may be prevented by skipping high doses and by carefully monitoring and modulating chelation, especially in patients with a low iron overload; (3) the maintenance of compliance with DFO over 0.6 and of ferritin levels below 2,000 prevents iron overloaded complications, at least for the first 20 years of life; (4) long-term chelation can reverse functional complications such as liver fibrosis, arrhythmia and echocardiographic abnormalities, but not complications due to extensive tissue alterations, such as frank diabetes, hypothyroidism and myocardiosclerosis; (5) intensive intravenous protocols can be successfully applied in heavily overloaded patients and represent the only possibility to reverse their dangerous iron burden in a relatively short period of time; (6) survival and quality of life in well-chelated patients are approaching a normal pattern, and (7) clinical outcome and prognosis are better evaluated by parameters that consider iron overload and chelation trends.
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PMID:Results of long-term iron-chelating therapy. 860 84

To compare two interferon (IFN) schedules for the treatment of chronic hepatitis C, we followed 211 patients who received 3 million units IFN-alpha2b thrice weekly for either 6 months (group 1; 85 patients) or 12 months (group 2; 126 patients), with a median follow-up of 3.4 (0.1-8.4) and 4.2 (0.7-8.7) years, respectively. The biochemical and virological responses at the end of treatment were 34.1% and 16.5% versus 62.7% and 41.2% for the 6- and the 12-month regimens, respectively. Late biochemical responses (after the third month of treatment) occurred in 30.6% of responding patients, and they were not particularly associated with an adverse long-term treatment outcome. In a multivariate analysis, patients with a primary response were significantly more frequently infected with a non-1b HCV genotype (relative risk [RR]: 14.4), had been treated for 12 months (RR: 6.0), and had an early stage of liver fibrosis (RR: 5.2). Baseline serum HCV-RNA and ferritin levels also bore a significant, though weaker, association with a primary response. Using a set of pretreatment variables in a model of discriminant analysis, we could correctly predict the long-term virological outcome in 86.6% of the individual cases. At the end of follow-up, a biochemical and virological sustained response was observed in 14.1% and 11.8% versus 40.5% and 31% of groups 1 and 2, respectively. Significant predictors of a virological sustained response were a virological primary response (RR: 41.2) and the pretreatment level of serum HCV-RNA (RR: 10.3 per each 10(6)-Eq/mL decrease). Patients with a "good treatment profile," including an early stage of liver fibrosis, a non-1b genotype and serum HCV-RNA <0.35 x 10(6) Eq/mL, had a 66.7% rate of observed virological SR, compared with a zero response for those with the opposite, a "bad treatment profile." We conclude that a 12-month IFN treatment, along with a non-1b genotype and the absence of advanced stage of fibrosis, are the main determinants for the induction of a virological primary response in chronic hepatitis C. Such response, along with a low pretreatment serum HCV-RNA level, are the main predictors for a 4-year virological response to IFN.
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PMID:Biochemical and virological outcome of patients with chronic hepatitis C treated with interferon alfa-2b for 6 or 12 months: a 4-year follow-up of 211 patients. 930 5

Oxidant stress plays a key role in hepatic fibrogenesis. This study was undertaken to assess whether, during iron overload-associated liver fibrosis in vivo, oxidant stress occurs in hepatic stellate cells (HSC) during active fibrogenesis. Gerbils were treated with iron-dextran, and, after hepatic fibrosis developed, livers were subjected to various combination of in situ hybridization and immunocytochemistry analyses. In iron-treated animals, no specific accumulation of ferritin protein was found in collagen mRNA-expressing cells. Moreover, the activity of the iron regulatory protein, the main sensor of cellular iron status, was unchanged in HSC from iron-treated animals. Although a significant amount of malondialdehyde-protein adducts was detected in gerbil liver during fibrogenesis, accumulation of these lipid peroxidation by-products was restricted to iron-laden cells adjacent to activated HSC. In cultured gerbil HSC, iron, aldehydes, and other pro-oxidants were able to enhance the expression of an oxidant stress-responsive gene, heme oxygenase (HO), with no change in collagen mRNA accumulation. In keeping with these findings, we found that, in vivo, activation of HO gene was present in iron-filled nonparenchymal cell aggregates, but absent in HSC. In conclusion, the data indicate that during iron overload-associated fibrogenesis, HSC are not directly subjected to oxidant stress, but are likely to be activated by paracrine signals arising in neighboring cells.
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PMID:Hepatic stellate cells are not subjected to oxidant stress during iron-induced fibrogenesis in rodents. 962 Mar 35

We describe liver fibrosis caused by iron overload after a long history of blood transfusion in a patient with chronic renal failure. Pertinent laboratory data were: serum (s)-Fe 148 microg/dl; unsaturated iron binding capacity (UIBC) 14 microg/dl; s-ferritin 9350 ng/ml; human leukocyte antigen (HLA) A2, A24, B39, B55, Cw1, Cw7. Computed tomography revealed a high density in the liver, and laparoscopy revealed a brown liver. Liver histology showed bridging fibrosis from portal tracts. A heavy iron deposit was seen in Kupffer cells as well as in hepatocytes surrounded by fibrosis around the portal tracts. Immunocytochemistry revealed alpha-smooth muscle actin in many stellate cells distributed along the fibrotic area, and electron microscopy revealed infiltrating myofibroblastic stellate cells coexisting with collagen fibers around degenerated hepatocytes containing iron deposits. The findings are consistent with the notion that stellate cells play an important role in liver fibrogenesis in both genetic and transfusional iron overload hemochromatosis.
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PMID:Activated hepatic stellate cells participate in liver fibrosis in a patient with transfusional iron overload. 977 45

The aim of this study was to set up an in vitro model for studying the importance of an altered extra-cellular matrix composition and its importance for the resistance to oxidative stress, in hepatocytes from normal and iron loaded rats. Primary cultures of hepatocytes from iron loaded and normal rats were plated on a laminin rich extracellular matrix or on collagen type I, and incubated with tert-butyl hydroperoxide (TBH). Malon dialdehyde (MDA) and the activities of lactate dehydrogenase (LDH) in cell culture medium were analyzed. The protein synthesis, the concentrations of glutathione and the expression of manganese-superoxide dismutase and ferritin genes were measured. All hepatocytes contained lower concentrations of glutathione when plated on collagen than on EHS. Ferritin H and Mn-SOD gene expression showed no difference. The rate of lipid peroxidation in iron loaded hepatocytes exposed to TBH was higher on collagen than in those plated on EHS (0.95 +/- 0.28 microM MDA vs. 1.62 +/- 0.22 microM MDA, p < 0.05). Iron loaded cells were in general more susceptible to TBH than were normal hepatocytes (MDA, LDH, protein synthesis and glutathione content). Lipid peroxidation could be prevented by adding desferrioxamine. In conclusion, we show that the combination of iron overload and collagen matrix in rat hepatocytes leads to an increased susceptibility to oxidative stress. These findings may be of interest for the further studies on effects of iron overload and the altered matrix composition in liver fibrosis.
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PMID:Susceptibility of cultured rat hepatocytes to oxidative stress by peroxides and iron. The extracellular matrix affects the toxicity of tert-butyl hydroperoxide. 1022 73

A unique organic form of iron (dicyclopentadienyl iron; ferrocene) has been used to further elucidate specific hepatic histopathologic, biochemical, and molecular parameters associated with dietary iron overload. Male C57BL/6Ibg mice fed a diet containing 0.04-0.2% w/w ferrocene for 115 days displayed severe hepatic siderosis of hepatocytes accompanied by a 15-fold induction of nonheme iron content compared to control mice receiving a diet with normal amounts of iron. The ferrocene treatment led to significant increases in hepatocellular necrosis as measured by plasma alanine aminotransferase activity. Histological assessment of hepatic fibrosis revealed mild increases in collagen deposition localized with accumulations of hemosiderin primarily in centrilobular hepatocytes. Hepatic fibrosis was confirmed by measurement of hepatic hydroxyproline content that was increased 4-fold in ferrocene-fed animals compared to control animals not ingesting ferrocene. Hepatic siderosis was accompanied by significant increases in hepatic malondialdehyde content suggesting the ferrocene-induced iron burden initiated lipid peroxidation in vivo. Expression of the heavy-chain isoform of ferritin mRNA and protein measured in liver after ferrocene feeding was increased approximately 8- and 2-fold, respectively, compared to the appropriate controls. These results, using an organic form of iron fed to genetically well-characterized inbred mice, provide new additional insight into the specific molecular and biochemical events that occur in association with histopathologic changes initiated by iron-induced liver injury. These data support the hypothesis that peroxidation of cellular membrane lipids is an important mechanism involved in the toxicity of excess hepatic iron and possibly the initiation of liver fibrogenesis. The results presented here also provide novel in vivo evidence documenting the cellular modulation of ferritin in response to the toxic effects of hepatic iron overloading and iron-mediated oxidative stress.
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PMID:Characterization of hepatic iron overload following dietary administration of dicyclopentadienyl iron (Ferrocene) to mice: cellular, biochemical, and molecular aspects. 1064 Apr 49

Genetic hemochromatosis is an autosomal recessive disease, characterized by an increased iron absorption, leading to progressive iron overload. The fully expressed phenotype comprises fatigue, skin pigmentation, liver disease with hepatomegaly, cirrhosis and hepatocellular carcinoma, and diabetes. Arthralgias are frequent, cardiopathy or impotence may occur. This presentation is now unfrequent with earlier diagnosis, and patients are often asymptomatic--with only biochemical expression--or pauci-symptomatic (mild fatigue, arthralgias or increased transaminases). Transferrin saturation is always increased. Serum ferritin is proportional to iron burden. Diagnosis is now easy, since most patients are homozygote for the C282Y mutation of the HFE gene. Liver biopsy can be useful to quantify iron overload and assess liver fibrosis. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.
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PMID:[Diagnosis and treatment of genetic hemochromatosis]. 1086 97


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