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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on an otherwise healthy female, mother of two children, with severe decompensated liver cirrhosis due to an iron overload and Wilson's disease. The patient was considered heterozygote for hemochromatosis on the basis of the autosomal recessive inheritance for hemochromatosis, the frequency of the hemochromatosis gene, and the laboratory parameters defining her iron overload. The case is interesting because of the coincidence of Wilson's disease and excessive iron storage.
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PMID:Excessive iron storage in a patient with Wilson's disease. 818 59

Tissue iron loading in hypotransferrinaemic (hpx/hpx) mice was investigated as a model for genetic (primary) haemochromatosis. Iron loading of liver preceded that in the pancreas and heart. One-year-old hpx/hpx mice showed iron staining in exocrine pancreas, liver parenchymal cells, and cardiac and intestinal smooth muscle cells. Iron-loaded macrophages were observed in all these tissues. Islets of Langerhans, biliary epithelial cells, and spleen were iron-free. The pancreas was fibrotic with massive macrophage infiltration and loss of secretory epithelium. Liver showed evidence of chronic inflammatory infiltration with increased collagen fibres in the parenchymal region but no cirrhosis. Serum aspartate aminotransferase activity and plasma glucose were increased in hpx/hpx compared with wild-type mice. Heavy iron loading with haemosiderin deposition in the liver could be demonstrated in hpx/hpx mice from 6 weeks of age. Heterozygous hypotransferrinaemic mice showed minor increases in liver iron stores at 6-12 weeks, but not at 1 year of age. Serum ferritin levels in heterozygous mice were also increased at 6-8 weeks of age. It was concluded that 1-year-old hpx/hpx mice showed evidence of liver and pancreatic damage secondary to tissue iron overload. The iron loading pattern and tissue damage showed some features which were distinct from those observed in haemochromatosis.
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PMID:Tissue iron loading and histopathological changes in hypotransferrinaemic mice. 827 72

Genetic haemochromatosis is an autosomal recessive inherited iron overload disease. The genetic defect and the underlying metabolic error are not known. Several observations indicate that the 2-4-fold increase of iron absorption is due to a regulatory defect of a membrane iron transport system in duodenal mucosal cells. The key pathophysiologic factor may be the increase of gut-derived non-transferrin bound iron liganded to low-molecular mass organic molecules. A putative membrane carrier protein for non-transferrin bound iron was identified and preliminary data suggest its enrichment in plasma membranes of human mucosal cells as well as in liver and other organs which are affected in genetic haemochromatosis. Cellular accumulation of ionic iron leads to peroxidative decomposition of organelle membrane phospholipids with the consequence of cell degeneration and cell death. Impairment of organ function and structural alterations such as cirrhosis of the liver are clinical manifestations.
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PMID:Pathogenesis of genetic haemochromatosis. 834 31

The authors reviewed T2-weighted and T2*-weighted abdominal magnetic resonance (MR) images in 19 pathology-proved cases of hepatic iron overload to compare patterns of iron distribution among cirrhotic and precirrhotic patients with idiopathic hemochromatosis (IH), as well as nontransfusional hepatic siderosis of other causes. Fifteen patients had clinical and laboratory evidence of IH. Four patients without IH had cirrhosis with moderate siderosis. In the MR images of all 19 patients, the liver had low signal intensity. The pancreas of 10 of 11 cirrhotic patients with IH had low signal intensity. All four precirrhotic patients with IH and all four cirrhotic patients without IH had pancreas with normal signal intensity at MR. Thus, pancreatic signal intensity was decreased only in cirrhotic patients with IH in this limited series. Conversely, pancreatic signal intensity is often normal in precirrhotic patients with IH prior to the development of cirrhosis, a stage at which definitive diagnosis by means of quantitative liver biopsy is important because early phlebotomy may prevent morbidity and mortality from IH. In cirrhotic patients with MR evidence of increased hepatic iron, the cause of cirrhosis is less likely to be IH if pancreatic signal intensity is normal.
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PMID:Idiopathic hemochromatosis: MR imaging findings in cirrhotic and precirrhotic patients. 835 25

The pathogenesis of hepatic fibrosis and cirrhosis in genetic hemochromatosis may involve a direct effect of excess iron on collagen synthesis in the liver. To investigate this theory, we measured procollagen messenger RNA levels (types I, III and IV) in the livers of rats in which we produced chronic parenchymal iron overload by feeding them dietary carbonyl iron (2.5%, wt/wt) for up to 18 mo. This feeding resulted in predominantly parenchymal iron deposition in a periportal distribution similar to that seen in genetic hemochromatosis. Increased amounts of collagen fibrils were observed in iron-loaded livers on electron microscopy; all iron-loaded livers showed some periportal fibrosis. Although very high hepatic iron concentrations (range = 340 to 1,100 mumol/gm dry wt) were achieved in the carbonyl iron-loaded rats, we saw no consistent difference between steady-state messenger RNA levels for procollagens types I, III and IV in control and iron-loaded livers examined at five different time points up to 18 mo. Messenger RNA levels of the cytokine transforming growth factor-beta 1, which has been implicated as having a role in the production of extracellular matrix proteins, were also measured. No significant differences were observed between iron-loaded and control livers. These results suggest that excess parenchymal iron does not have a direct effect on the expression of the procollagens or transforming growth factor-beta 1 genes in iron-loaded livers and that factors other than, or in addition to, iron are necessary for fibrosis to occur.
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PMID:Effect of chronic iron overload on procollagen gene expression. 835

We report a case of a posttransplant lymphoproliferative disorder (PTLD) which presented in a liver allograft shortly after transplantation. The patient, who had been transplanted because of cirrhosis due to primary hemochromatosis and chronic hepatitis B infection (HBV), developed early recurrent HBV in the graft, and 2 months after transplantation, liver biopsies showed a malignant large-cell lymphoma. The neoplastic cells demonstrated Epstein-Barr virus DNA by in situ hybridization. The patient died 3.5 months posttransplant due to liver failure. At autopsy, the liver showed nodules of malignant lymphoma, massive hepatic necrosis, and iron overload, but no evidence of rejection. This report suggests that the grafted liver can be the site of PTLD in recurrent HBV and hemochromatosis.
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PMID:Rapid development of lymphoma following liver transplantation in a recipient with hepatitis B and primary hemochromatosis. 838 May 33

Magnetic resonance imaging provides excellent anatomic depiction of the liver and important information about focal and diffuse diseases that affect this organ. In this report, the current clinical applications of magnetic resonance imaging of the liver in patients with known or suspected hepatic metastatic lesions, hepatocellular carcinoma, cavernous hemangiomas, focal fatty infiltration, focal nodular hyperplasia, hepatic adenoma, regenerative nodules in hepatic cirrhosis, or iron overload are reviewed, and the limitations of the technique are discussed.
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PMID:Magnetic resonance imaging of the liver: current clinical applications. 842 95

The diagnosis of homozygous hemochromatosis (HH) should be based on appropriate findings on liver biopsy specimens. In cases with equivocal morphologic features, quantitative tissue iron determination and calculation of the hepatic iron index generally enable one to distinguish HH from other types of hepatic iron overload. In this article, we describe a diagnostic algorithm that is designed to avoid diagnostic errors because of histologic misinterpretation or erroneous, usually false-negative, chemical iron studies. The algorithm also delineates a cost-effective method of using quantitative tissue iron analysis. Diagnostic biopsy features of uncomplicated HH include (1) hemosiderosis that involves primarily hepatocytes, with or without inactive cirrhosis, and (2) a tissue iron index of 1.9 or higher. Findings such as prominent fatty changes or lymphocytic piecemeal necrosis indicate the presence of HH in conjunction with another complicating condition or secondary iron overload in the absence of HH.
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PMID:Liver biopsy diagnosis of homozygous hemochromatosis: a diagnostic algorithm. 847 69

We investigated the iron status of 33 pyruvate kinase (PK) deficient patients, most of the cases reported in Italy. Serum ferritin (SF) was higher than the upper limit of the range of matched controls in 15/25 (60%) non-transfused patients (median 228 micrograms/l, range 58-3160 v 43, 22-310). Liver siderosis and fibrosis were found in 8/9, and cirrhosis in two who died at age 39 and 42 of complications of iron overload. SF was independent of age, sex, or severity of haemolysis. The prevalence of HLA-A3 antigen in PK deficient patients was not significantly different from that of our healthy population (29.6% v 23%). The HLA-A3 positive, non-transfused patients had significantly higher SF values than the HLA-A3 negative ones (median 675 micrograms/l, range 340-3160 v 145, 58-400). A pedigree study of six high SF-probands indicated that iron overload has a multifactorial pathogenesis. In particular, the association of PK deficiency-induced haemolysis, splenectomy and an additional factor (heterozygosity for idiopathic haemochromatosis, ineffective erythropoiesis) leads to severe iron accumulation. We suggest that monitoring iron status would be useful in PK deficient patients, particularly in splenectomized and HLA-A3 positive ones, to identify those at risk of iron overload and prevent the clinical consequences of iron accumulation.
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PMID:Iron status in red cell pyruvate kinase deficiency: study of Italian cases. 848 56

Although essential for life, iron in excessive amounts may be toxic. The liver is particularly subject to the toxic effects of iron, since it is the major site of iron storage. Several inherited and acquired human disorders may result in hepatic iron overload, the most common of which are genetic hemochromatosis (GH) and transfusional iron overload. GH is an inherited disorder of iron metabolism, and in patients with GH excess iron absorbed from the gut is transported through the portal vein to the liver. The mechanisms by which excess iron exerts its cytotoxic effects include enhanced formation of free radicals and peroxidation of organelle membrane lipids. Lipid peroxidation can lead to structural and functional alterations in lysosomes, mitochondria and the endoplasmic reticulum. With massive iron overload, such iron-induced alterations may cause cell death, also known as sideronecrosis. At this stage, fibrogenesis is initiated and, if the excess iron is not removed, the increased deposition of collagen progresses to cirrhosis. However, the mechanisms underlying iron-induced fibrosis remain unclear. Transformation of fat-storing cells to collagen-producing myofibroblasts has been proposed to be induced either by iron; by lipid peroxides or other cellular factors released from iron-loaded, damaged hepatocytes; or by profibrogenic factors produced by activated Kupffer cells. In addition, iron may enhance the cytotoxic and, possibly, fibrogenic effects of other liver cell-damaging agents, such as alcohol or hepatotrophic viruses. Once cirrhosis is manifest, patients with GH demonstrate a 200-fold increase in the risk for development of hepatocellular carcinoma. In vitro, iron has been shown to possess mutagenic properties, but the results from in vivo models in which the genotoxic effects of iron overload have been studied are variable. Similarly, although iron has mitostimulatory effects on hepatocytes in vivo and preneoplastic cells in vitro, its role in tumor promotion and/or progression still remains unclear. Cirrhosis itself is of central importance in the carcinogenic process, but whether or not iron acts as an additional risk factor in this process, alone or by enhancing the tumorigenic properties of other hepatocarcinogens, has yet to be established.
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PMID:Iron as a hepatotoxin. 852 7


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