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

The liver is the main storage site for iron in the body. Excess accumulation of iron in the liver has been well-documented in two human diseases, hereditary hemochromatosis and dietary iron overload in the African. Hepatic iron overload in these conditions often results in fibrosis and cirrhosis and may be complicated by the development of hepatocellular carcinoma. Malignant transformation usually occurs in the presence of cirrhosis, suggesting that free iron-induced chronic necroinflammatory hepatic disease plays a role in the hepatocarcinogenesis. However, the supervention of hepatocellular carcinoma in the absence of cirrhosis raises the possibility that ionic iron may also be directly hepatocarcinogenic. Support for this possibility is provided by a recently described animal model of dietary iron overload in which iron-free preneoplastic nodules and hepatocellular carcinoma developed in the absence of fibrosis or cirrhosis. The mechanisms by which iron induces malignant transformation have yet to be fully characterized but the most important appears to be the generation of oxidative stress. Free iron generates reactive oxygen intermediates that disrupt the redox balance of the cells and cause chronic oxidative stress. Oxidative stress leads to lipid peroxidation of unsaturated fatty acids in membranes of cells and organelles. Cytotoxic by-products of lipid peroxidation, such as malondialdehyde and 4-hydroxy-2'-nonenal, are produced and these impair cellular function and protein synthesis and damage DNA. Deoxyguanosine residues in DNA are also hydroxylated by reactive oxygen intermediates to form 8-hydroxy-2'-deoxyguanosine, a major promutagenic adduct that causes G:C to T:A transversions and DNA unwinding and strand breaks. Free iron also induces immunologic abnormalities that may decrease immune surveillance for malignant transformation.
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PMID:Hepatic iron overload and hepatocellular carcinoma. 1908 72

This review highlights recent advances in hepatology, including new insights into the clinical penetrance of hereditary hemochromatosis, the development of non-immunosuppressive cyclosporin A analogs for the treatment of chronic hepatitis C, thrombopoietin receptor agonists for thrombocytopenia in cirrhosis, the development of vasopressin V2 receptor antagonists (vaptans) for the management of ascites and hyponatremia in portal hypertension, the description of chronic hepatitis E in immunosuppressed patients, and the development of sorafenib as the first molecularly targeted therapy with a demonstrated benefit in the treatment of advanced hepatocellular carcinoma. These new developments will be summarized and discussed critically, with a particular emphasis on their potential implications for current and future clinical practice.
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PMID:[Highlights in hepatology]. 1927 30

In populations of northern European descent, the p.C282Y mutation in the HFE gene is highly prevalent, and HFE-associated hereditary hemochromatosis is the most common type of inherited iron overload disorder. Inappropriate low secretion of hepcidin, which negatively regulates iron absorption, is postulated to be the mechanism for iron overload in this condition. The characteristic biochemical abnormalities are elevated serum transferrin-iron saturation and serum ferritin. Typical clinical manifestations include cirrhosis, liver fibrosis, hepatocellular carcinoma, elevated serum aminotransferase levels, diabetes mellitus, restrictive cardiomyopathy and arthropathy of the second and third metacarpophalangeal joints. Most patients are now diagnosed before the development of these clinical features. Molecular genetic tests are currently available for genotypic diagnosis. In selected individuals, diagnosis might require liver biopsy or quantitative phlebotomy. Iron depletion by phlebotomy is the mainstay of treatment and is highly effective in preventing the complications of iron overload if instituted before the development of cirrhosis. Genetic testing is currently not recommended for population screening because of low yield as the majority of the healthy, asymptomatic p.C282Y homozygotes do not develop clinically significant iron overload. HFE gene testing remains an excellent tool for the screening of first-degree relatives of affected probands who are p.C282Y homozygotes.
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PMID:HFE-associated hereditary hemochromatosis. 1944 13

Although chronic infection with hepatitis B virus and/or hepatitis C virus are the most important risk factors for hepatocellular carcinoma (HCC) worldwide, other causes of cirrhosis can also lead to HCC. Given the high prevalence of alcoholism and the worldwide obesity epidemic, the relevant importance of nonviral liver disease-related HCC is expected to increase in the future. Some evidence supports mechanistic interactions between host or environmental factors and chronic viral hepatitis in the development of HCC. For example, food- and water-borne carcinogens have contributed to unusually high rates of HCC in parts of China and sub-Saharan Africa. With some of these conditions, appropriate public health measures to reduce the population's exposure to known etiologic agents, or early therapeutic intervention for 'at-risk' individuals before development of cirrhosis (e.g. hereditary hemochromatosis) can prevent HCC. Community-based programs to discourage and deal with excessive alcohol intake, to promote tobacco smoking awareness, to avoid exposure to aflatoxin and other food toxins, and measures to reduce the pandemic of obesity and diabetes are vital for effective interruption of the rising tide of HCC from nonviral liver disease.
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PMID:Prevention of hepatocellular carcinoma in nonviral-related liver diseases. 1964 14

Chronic hepatitis B is a frequent concomitant disease in recipients of a renal graft that worsens results of kidney transplantation due to renal and extrarenal complications. Much rarer hemochromatosis either has genetic roots (hereditary hemochromatosis) or results from multiple blood transfusions and hemolysis during treatment by hemodialysis (secondary hemochromatosis). Combination of chronic hepatitis B and hemochromatosis increases the risk of chronic liver disease leading to cirrhosis and hepatocellular carcinoma. Success of antiviral therapy combined with massive phlebotomy is illustrated by a case of kidney transplantation to a patient with chronic hepatitis B of large duration and iron overload syndrome.
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PMID:[Chronic hepatitis B, hemosiderosis, and hepatic fibrosis in a renal graft recipient]. 1967 Jul 22

Iron is a crucially important element in normal cellular function and thus the regulation of iron homeostasis is tightly controlled. When this regulation is disrupted, for instance in hereditary hemochromatosis, abnormal intestinal absorption of iron leads to cellular toxicity, tissue injury, and organ fibrosis via the deposition of this iron in parenchymal cells of a number of different organs such as the heart, pancreas, and liver. Iron-generated oxyradicals contribute to the peroxidation of lipid membranes leading to organelle fragility and cellular toxicity. This process is thought to contribute to hepatocellular necrosis and/or apoptosis in the liver with the subsequent activation of hepatic stellate cells and the development of hepatic fibrosis and cirrhosis. Understanding the processes associated with normal iron homeostasis is crucially important as this will ultimately provide clues as to how altered iron uptake and delivery leads to tissue injury and organ dysfunction in diseases of disordered iron metabolism. This review highlights recent advances in identifying major regulators associated with hepatic iron homeostasis and examines the potential mechanisms involved in the development of iron overload-induced hepatic injury and fibrogenesis.
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PMID:Iron homeostasis, hepatocellular injury, and fibrogenesis in hemochromatosis: the role of inflammation in a noninflammatory liver disease. 2066 79

Iron-induced oxidative stress promotes hepatic injury in hereditary hemochromatosis, which can be influenced by genetic traits affecting antioxidant enzymes. We assessed the influence of Ala16Val-superoxide dismutase 2, Pro198Leu-glutathione peroxidase 1, and -463G/A-myeloperoxidase genotypes (high activity for the Ala, Pro, and G alleles, respectively) on the risks of cirrhosis and hepatocellular carcinoma (HCC) in patients homozygous for the C282Y-hemochromatosis (HFE) gene mutation. Both the 2G-myeloperoxidase genotype and carriage of one or two copies of the Ala-superoxide dismutase 2 allele were more frequent in patients with cirrhosis or HCC. Patients cumulating these two genetic traits had higher rates of cirrhosis and HCC than other patients.
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PMID:Do genetic variations in antioxidant enzymes influence the course of hereditary hemochromatosis? 2067 59

Hereditary hemochromatosis (HH) refers to several inherited disorders of iron metabolism leading to tissue iron overload. Classical HH is associated with mutations in HFE (C282Y homozygotes or C282Y/H63D compound heterozygotes) and is almost exclusively found in populations of northern European descent. Non-HFE-associated HH is caused by mutations in other recently identified genes involved in iron metabolism. Hepcidin is an iron regulatory hormone that inhibits ferroportin-mediated iron export from enterocytes and macrophages. Defective hepcidin gene expression or function may underlie most forms of HH. Target organs and tissues affected by HH include the liver, heart, pancreas, joints, and skin, with cirrhosis and diabetes mellitus representing late signs of disease in patients with markedly elevated liver iron concentration. Recently, we have encountered the rare representation of this disease of the oral cavity associated with generalized burning sensation of the tongue. The diagnosis was established accidently, from the lab investigations, otherwise the patient was healthy and free from classical signs and symptoms of the disease. The patient was adequately treated by phlebotomy. To conclude, all patients with a chief complaint of burning sensation of the oral cavity and tongue should be adequately screened for hereditary hemochromatosis to prevent the associated mortality and morbidity with the hemochromatosis.
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PMID:Hereditary hemochromatosis of tongue. 2117 7

Hemochromatosis is a genetic disorder of iron metabolism that results in elevated iron absorption in the intestines, which leads to progressive iron accumulation in a variety of organs. Studies have shown that excessive iron deposits in the liver due to hereditary hemochromatosis leads to cirrhosis, which can put an individual at increased risk for developing hepatocellular carcinoma. Testicular atrophy, sometimes caused by excessive iron deposition in the testes, is a risk factor for testicular cancer. Therefore, the possible role of hereditary hemochromatosis in testicular cancer is explored.
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PMID:The possible role of hemochromatosis in testicular cancer. 2154 11

Patients with liver cirrhosis have increased risk of diabetes mellitus development, especially when the underlying disease is hereditary hemochromatosis, autoimmune hepatitis, non-alcoholic steatohepatitis or chronic hepatitis C. Patients with associated diabetes according to liver cirrhosis complications have worse prognosis and the therapy is influenced by both diseases. The authors bring short review of particular diseases, diagnosis and treatment strategy.
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PMID:[Diabetes mellitus and the liver cirrhosis]. 2161 60


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