Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic hemosiderosis and increased iron absorption are common findings in cirrhosis. It has been proposed that a positive relation exists between intestinal iron absorption and the development of hepatic hemosiderosis. The current study investigated the duodenal expression of the iron transport molecules divalent metal transporter 1 (DMT1 [IRE]), iron-regulated gene 1 (Ireg1 [ferroportin]), hephaestin, and duodenal cytochrome b (Dyctb) in 46 patients with cirrhosis and 20 control subjects. Total RNA samples were extracted from duodenal biopsy samples and the expression of the iron transport genes was assessed by ribonuclease protection assays. Expression of DMT1 and Ireg1 was increased 1.5 to 3-fold in subjects with cirrhosis compared with iron-replete control subjects. The presence of cirrhosis per se and serum ferritin (SF) concentration were independent factors that influenced the expression of DMT1. However, only SF concentration was independently associated with Ireg1 expression. In cirrhosis, the expression of DMT1 and Ireg1 was not related to the severity of liver disease or cirrhosis type. There was no correlation between the duodenal expression of DMT1 and Ireg1 and the degree of hepatic siderosis. In conclusion, the presence of cirrhosis is an independent factor associated with increased expression of DMT1 but not Ireg1. The mechanism by which cirrhosis mediates this change in DMT1 expression has yet to be determined. Increased expression of DMT1 may play an important role in the pathogenesis of cirrhosis-associated hepatic iron overload.
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PMID:Increased duodenal expression of divalent metal transporter 1 and iron-regulated gene 1 in cirrhosis. 1476 3

Hypogonadism, usually hypogonadotropic in origin, is the most common nondiabetic endocrinopathy in hereditary hemochromatosis (HH). Early studies, usually evaluating small numbers of patients with advanced HH, report prevalence rates of 10-100%. The clinical presentation of HH has changed in recent years as a result of increased awareness and screening. We assessed the prevalence of hypogonadism in a large group of patients with HH diagnosed in a single center over the past 20 yr, the period of follow-up spanning the time before and after widespread screening was introduced and the HFE gene was recognized. Abnormally low plasma testosterone levels, with low LH and FSH levels, were found in nine of 141 (6.4%) male patients tested. Eight of nine (89%) had associated hepatic cirrhosis; three of nine (33%) had diabetes. Inappropriately low LH and FSH levels were found in two of 38 females (5.2%) in whom the pituitary-gonadal axis could be assessed. This is the largest detailed study of hypogonadism reported in HH. The lower prevalence of hypogonadism compared with other reported series reflects the earlier diagnosis of HH in an unselected group of patients attending a single center. Patients with lesser degrees of hepatic siderosis at diagnosis are unlikely to develop hypogonadism.
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PMID:Hypogonadism in hereditary hemochromatosis. 1565 76

Since the discovery of HFE gene in 1996, considerable progress has been made concerning the iron-metabolism and its major abnormalities. Five types of hereditary hemochromatosis are actually known: type 1 (HFE gene), type 2A (HJV gene), type 2B (HAMP gene), type 3 (TfR2 gene), type 4 (SLC40A1 gene). The HFE C282Y +/+ mutation is responsible for the most frequent type of hemochromatosis in France. Various secondary causes can lead to iron-overload: associated genetic diseases, exogenous iron intake, thalassaemia and refractory anaemia, hepatic siderosis, alcoholic hepatitis, cutaneous porphyria and cirrhosis. The deleterious consequences of iron-overload are due to the interactions of the environmental factors. The role of HFE heterozygote mutations is still discussed. In clinical practice, the interpretation of a serum ferritin increase is a frequent problem that needs a careful evaluation based on the tranferrin saturation measurement. Significant increase of both these factors is in favour of an HFE C282Y +/+ hemochromatosis, after exclusion of a hepatocellular insufficiency or a refractory anaemia. Nevertheless, high ferritin is not always a marker of iron-overload. Thus, there are many disorders increasing the serum ferritin levels without iron overload : cytolysis (hepatic...), inflammatory or infectious syndromes, high alcohol intake, neoplasia... Looking for HFE mutations help to separate type 1 hemochromatosis from other conditions mainly hepatic siderosis (metabolic disorders). The identification of rare types of hemochromatosis (types 2-4) is only required in particular cases. The evaluation of the iron overload is now based on hepatic MRI determination rather than liver biopsy. Repeated phlebotomies remain the essential way to decrease the iron overload in HFE hemochromatosis and to prevent the occurrence of severe and irreversible complications (cirrhosis, arthropathies, cardiac failure, and diabetes). Because of the link established between the amount of iron-overload and the occurrence of complications and the mortality over-risk in HFE C282Y +/+ hemochromatosis, venesections must be started when serum ferritin is higher than 300 microg/l in man and 200 microg/l in woman, whatever the clinical manifestations are and obviously before the symptomatic phase of the disease.
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PMID:[Hereditary and acquired iron overload]. 1737 75

Iron overload is characterised by excessive iron deposition and consequent injury and dysfunction of target organs, especially the heart, liver, anterior pituitary, pancreas and joints. Iron overload disorders are common worldwide and occur in most major race/ethnicity groups. Physiological mechanisms to excrete iron are very limited. Thus, all patients with iron overload need safe and effective treatment that is compatible with their co-existing medical conditions. Treatments for iron overload include phlebotomy and erythrocytapheresis that remove iron predominantly as haemoglobin, and chelation therapy with drugs that bind excess iron selectively and increase its excretion. The most important potential benefits of therapy are preventing deaths due to cardiac siderosis and hepatic cirrhosis. Preventing iron-related injury to endocrine organs is critical in children. Successful treatment or prevention of iron overload increases quality of life and survival in many patients. This article characterises the major categories of iron overload disorders, tabulates methods to evaluate and treat iron overload, and describes treatment options for iron overload disorders. Research needed to advance knowledge about treatment of iron overload is proposed.
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PMID:Optimal management strategies for chronic iron overload. 1738 41

Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful (1) to assess prognosis by grading fibrosis and seeking for associated lesions and (2) to guide the etiological diagnosis, especially when no molecular marker is available. Then, the type of liver siderosis (parenchymal, mesenchymal or mixed) and its distribution throughout the lobule and the liver are useful means for suggesting its etiology: HLA-linked hemochromatosis gene (HFE) hemochromatosis or other rare genetic hemochromatosis, nonhemochromatotic genetic iron overload (ferroportin disease, aceruloplasminemia), or iron overload secondary to excessive iron supply, inflammatory syndrome, noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders.
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PMID:Pathology of hepatic iron overload. 1772 97

Hepatic siderosis is frequent in patients with Hepatitis C virus (HCV) chronic hepatitis and considered secondary to advanced liver disease when detected in the explanted liver of cirrhotic patients submitted to transplantation. Here, we document the early recurrence of hepatic iron overload starting from host Kupffer cells and later involving hepatocytes in an Italian male submitted to liver transplantation for HCV-related cirrhosis, whose hemosiderosis was interpreted as related to a primary defect of iron handling by monocytic cells due to decreased Ferroportin-1 expression. He was negative for HFE mutations, had normal liver function, did not drink alcohol and had no erythropoietic defect. He was positive for the (CGG)(8/9) and the IVS1 -24 G>C Ferroportin-1 polymorphisms, associated with non-parenchymal iron overload, and had decreased Ferroportin-1 expression in monocytes. In conclusion, this case report documents the recurrence of progressive liver siderosis, which recalls Ferroportin disease, associated with decreased Ferroportin-1 expression in host monocytes repopulating the donor liver.
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PMID:Ferroportin-1 in the recurrence of hepatic iron overload after liver transplantation. 1833 95

Hepatocellular carcinoma (HCC), following liver cirrhosis as a complication of chronic hepatitis B or C viruses (HBV or HCV)and iron overload, has been reported in thalassemia patients. This study assessed HCC incidences, the role of iron and possible antitumor activity of chelators in 57 thalassemia major (TM) and nine thalassemia intermedia (TI) patients using deferoxamine (DFO) therapy. Antibodies against HCV were detected in 23/57 (40.4%) TM patients, chronic HCV and cirrhosis were diagnosed in 13/23 (56.5%), 7/12 did not respond to antiviral therapy and 2/7 progressed to HCC (incidence 2/57, 3.5%). Three (33.3%) TI patients with liver siderosis and fibrosis and late introduction of iron chelation developed HCC without a history of hepatitis. The incidence was higher in TI (p = 0.032). The main risk factor for HCC was HCV infection in TM patients but it was iron activity in TI patients. Iron chelation with DFO appeared to play a protective role.
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PMID:Incidence of hepatocellular carcinoma in a thalassemia unit. 2052 12

In thalassemia major, iron overload is the joint outcome of multiple blood transfusions and an inappropriately increased iron absorption associated with ineffective erythropoiesis. Threshold values for iron toxicity are a liver iron concentration exceeding 440 mmoles/g dry weight, serum ferritin >2500 ng/mL, DFO urinary iron excretion >20 mg/day, and transferrin saturation >75%. The outpouring of catabolic iron that exceeds the iron-carrying capacity of transferrin results in the emergence of non-transferrin-bound iron (NTBI). NTBI is cleared preferentially by the liver and myocardium at a rate exceeding 200 times that of transferrin iron. NTBI catalyzes the formation of free radicals, resulting in oxidative stress and damage to mitochondria, lysosomes, lipid membranes, proteins, and DNA. The long-term consequences of iron toxicity, including cirrhosis, myocardiopathy, and endocrine disorders, are preventable and mostly reversible by effective iron chelation therapy. Recent technologic advances in the documentation of organ-specific siderosis and the improved efficiency of iron chelating programs resulted in a spectacular improvement in the prevention of iron-induced end-organ failure and improved survival in thalassemic patients.
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PMID:Pathogenesis and management of iron toxicity in thalassemia. 2071 65

The study was based on the biopsy material collected in Eastern coastal region of South Africa with high incidence of primary hepatocellular carcinoma (HCC). Forty-one patients were between 9 and 25 years old of the total number of 474 cases of HCC available for examination. Liver biopsies were fixed in 10% of neutralised formalin, processed to paraffin blocks, cut and stained with hematoxylin and eosin, silver reticulin, Masson trichrome and Prussian blue stains. Representative biopsies of 21 patients younger than 25 years and 56 older than 35 years were in addition examined immunohistochemically with HBsAg antibody, endothelial marker (F VIII-related antigen) and for oncoproteins c-myc and c-erbB-2 using peroxidase-antiperoxidase method. Cirrhotic liver was evident in 41.5% of all patients and in 28% of younger than 25 years. Hemosiderosis of the liver of patients over 35 years was nearly twice as common as in younger than 25 years and showed the opposite relationship to the presence of HBsAg in liver tissue. Oncoprotein expression was also higher in tumor tissue of younger patients. These results indicate the etiological association of HCC with HBV infection, cirrhosis and possibly siderosis of the liver with HCC. Simultaneous expression of oncoproteins and HBsAg indicate the primary importance of viral infection in etiopathogenesis of HCC.
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PMID:Hepatocellular carcinoma in young patients. 2159 36

In addition to focal liver lesions, diffuse and vascular disorders of the liver represent a wide spectrum of liver diseases which are from the radiological point of view often difficult or nearly impossible to diagnose. Classical diagnostic methods are computed tomography and magnetic resonance imaging in addition to ultrasound. Diffuse parenchymal damage caused by diseases of various etiologies is therefore difficult to evaluate because it often lacks characteristic morphological features. For hepatic steatosis, hemochromatosis/siderosis as an example of a diffuse storage disease and sarcoidosis and candidiasis as infectious/inflammatory diseases, an image-based diagnosis is appropriate in some cases. For most diffuse liver diseases, however only nonspecific changes are visualized. Vascular pathologies of the liver, such as the Budd-Chiari syndrome and portal vein thrombosis, however, can usually be diagnosed very clearly using radiology and there is also a very effective interventional radiological treatment. Chronic diseases very often culminate in liver cirrhosis which is highly associated with an increased risk of liver cancer.
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PMID:[Diffuse and vascular hepatic diseases]. 2180 55


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