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)

The reliability of serum iron, transferrin saturation, and serum ferritin in the detection of early iron overload in hemochromatosis was determined in 120 young (less than 35 yr old) relatives whose genetic susceptibility for the disease was determined by HLA typing of families. Serum ferritin and transferrin saturation demonstrated high levels of sensitivity and specificity, whereas serum iron concentration was an unreliable test in the detection of hemochromatosis. In hemochromatosis homozygotes there was an excellent correlation between serum ferritin and mobilized body iron (r = 0.92), 1 microgram/L of serum ferritin corresponding to approximately 7.5 mg of body iron stores. For a given age, serum ferritin values were higher in homozygotes compared with heterozygotes or homozygous-normal subjects and increased by approximately 65 micrograms/L X yr, reflecting the progressive accumulation of iron in hemochromatosis homozygotes. All hemochromatosis subjects with either hepatic fibrosis or cirrhosis had serum ferritin concentrations greater than 700 micrograms/L. We conclude that the combination of serum ferritin and transferrin saturation is a reliable screening regimen for the detection of hemochromatosis and for predicting the level of body iron stores in young hemochromatosis subjects.
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PMID:Diagnosis of hemochromatosis in young subjects: predictive accuracy of biochemical screening tests. 674 16

Severe hemolytic in Basenji dogs secondary to pyruvate kinase deficiency was corrected by marrow transplantation from hematologically normal littermates. These dogs have now been followed for more than 5.5 yr. Essentially normal hematopoiesis has persisted, and the dogs remain in good health without cirrhosis or osteosclerosis. Furthermore, hepatic iron overload present before transplantation has gradually decreased. These results in dogs suggest that marrow transplantation could prevent the morbidity and mortality of severe hemolytic anemia and associated iron overload in man.
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PMID:Long-term survival and reversal of iron overload after marrow transplantation in dogs with congenital hemolytic anemia. 677 39

The traditional alcoholic beverages drunk by many South African blacks are prepared in iron drums, and, as a result, iron overload is common in this population. The typical pattern of iron distribution in such persons with severe iron overload is one in which the major deposits are in hepatocytes and the reticuloendothelial system. However, when cirrhosis is present, significant epithelial deposits are found in a number of organs. In the present study, the synovium of the knee joint was examined in 41 black subjects and synovial iron deposits, when present, were correlated with those in other organs. Significant amounts of iron in the synovial-lining cells were not found in any subject in whom the hepatic iron concentration was less than 1% dry weight. Heavy deposits, which were found in six of 19 subjects with concentrations above this figure, only occurred in those exhibiting cirrhosis and significant levels of histological iron in a number of epithelial tissues. Insofar as iron uptake is concerned, these findings suggest that there are cells within the synovium that have the functional characteristics of epithelial cells.
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PMID:Synovial iron deposits in black subjects with iron overload. 689 21

Severe iron overload developed in two patients with congenital erythrocyte pyruvate kinase deficiency. In one of them this was complicated by hepatic cirrhosis and endocrine dysfunction. In both patients, the institution of intermittent subcutaneous administration of desferrioxamine resulted in significant urinary iron excretion and a reduction in the degree of iron overload.
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PMID:Iron overload in congenital erythrocyte pyruvate kinase deficiency. 739 32

Clinically, portal hypertension has been considered to be less common and less severe in patients with cirrhosis resulting from iron overload in homozygotes for genetic hemochromatosis than in patients with cirrhosis of other causes. To characterize the prevalence and progression of portal hypertension in genetic hemochromatosis (GH), 120 cirrhosis and iron-overloaded patients were compared with a control group of 120 patients with postnecrotic cirrhosis (PNC) who were matched for gender, age, Child's class, and alcohol abuse. Gastroesophageal endoscopy and abdominal ultrasonography were performed at diagnosis and repeated every 12 months and every 6 months, respectively, to evaluate the presence and severity of varices, the caliber of the portal vein and its collaterals, and splenic size. At diagnosis a similar frequency of varices was observed in patients with GH (25%) and in PNC (24%), as well as of portal vein abnormalities and spleen enlargement. During the follow-up period, all but two of the patients with GH were treated by phlebotomy and depleted of excess iron. After a mean of 6 +/- 4.3 (SD) years of observations (range, 2 to 10 years), varices were improved or completely reversed in 26% of patients with cirrhosis and GH but in only 5% of those with PNC (P < .01). Bleeding from varices was observed in only one patient with GH but in five patients with PNC. Of 22 patients with GH in whom portal hypertension was unmodified or worsened, 16 had coexistent hepatic viral infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Portal hypertension and iron depletion in patients with genetic hemochromatosis. 755 61

A common characteristic of patients with porphyria cutanea tarda (PCT) is liver dysfunction. The degree of liver damage is usually mild but liver cirrhosis is a common associated finding. Hepatic iron overload is a characteristic feature but the role of iron in the pathogenesis of the condition has not yet been clarified. Heavy alcohol consumption is a frequent precipitant of PCT. A strong association with markers of past hepatitis B virus infection was first demonstrated but a high prevalence of hepatitis C virus markers is now noted. Although the potential to give rise to hepatocellular carcinoma (HCC) in PCT patients with cirrhosis is well recognized, HCC itself has a risk of developing PCT. HCV or the cirrhotic change itself has been attributed as the risk factor for the occurrence of HCC.
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PMID:[Association of cirrhosis and hepatocellular carcinoma with porphyria cutanea tarda]. 761 64

The mechanisms underlying iron-induced liver fibrogenesis in patients with genetic hemochromatosis are poorly understood. We studied signs of Kupffer cell activation and inflammatory responses in liver biopsy specimens obtained from 15 patients with untreated and six patients with treated hemochromatosis. Immunohistochemistry was performed on 11 of the untreated and all treated patients. Three of the untreated patients (20%) had cirrhosis and eight (53%) had fibrosis. None had chronic active hepatitis (CAH). Immunohistochemistry indicated that 55% of the untreated patients had sparse intercellular adhesion molecule-1 (ICAM-1) expression by hepatocytes, and all of these had Kupffer cell iron overload. No ICAM-1 expression was seen by hepatocytes in treated patients or healthy controls. ICAM-1 was strongly expressed by hepatocytes from control patients with inflammatory liver disease. HLA-DR reactivity was seen on sinusoidal cells in all groups, but not on hepatocytes except for two of the control patients with CAH. Twenty-seven percent of the untreated hemochromatosis patients displayed moderate infiltration by CD3-positive lymphocytes. Electron microscopy of samples from untreated hemochromatosis patients showed hypertrophic Kupffer cells containing iron-rich remnants of phagocytosed hepatocytes. Fat-storing cells close to iron-laden hepatocytes contained multiple lipid droplets and adjacent collagen fibril bundles. Thus, in patients with untreated genetic hemochromatosis and Kupffer cell iron overload, hepatocytes occasionally express ICAM-1. In regions with heavy iron overload, Kupffer cell hypertrophy and transition of fat-storing cells are seen. Our findings indicate that release of factors from iron-loaded, activated Kupffer cells is of importance for the transformation of fat-storing cells and increased collagen deposition seen in genetic hemochromatosis.
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PMID:Kupffer cell iron overload induces intercellular adhesion molecule-1 expression on hepatocytes in genetic hemochromatosis. 773 36

44 patients with a range of parenchymal liver diseases diagnosed by biopsy or laboratory investigations underwent proton nuclear magnetic resonance (NMR) relaxometry of the liver at 0.08 T. T1 maps were produced using an interleaved saturation recovery and inversion recovery sequence and T2 maps using a four echo Carr-Purcell-Meiboom-Gill sequence. Significantly raised relaxation times compared with a previously studied group of 42 normal volunteers were found in groups of patients with alcoholic cirrhosis (p < 0.001 for T1 and T2), chronic active hepatitis (CAH) (p < 0.01 for T1 and T2) and minor liver abnormalities (p < 0.01, T2 only). T1 was significantly higher in cirrhotics than in patients with CAH (p < 0.002) and minor abnormalities (p < 0.001). This suggests a role for relaxometry in the confirmation of the presence of cirrhosis (sensitivity = 75%, specificity approximately 97%, taking T1 > 266 ms as a positivity criterion). Reduced T2 values were found in patients with liver iron overload prior to venesection (p < 0.001 versus normals, p < 0.02 versus venesected patients). Although this latter test has relatively low sensitivity and specificity, it may have a role in the monitoring of treatment for iron overload.
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PMID:Non-invasive assessment of diffuse liver disease by in vivo measurement of proton nuclear magnetic resonance relaxation times at 0.08 T. 782 Apr

Hereditary hemochromatosis (HFE) is an inherited recessive disorder which causes progressive iron overload. Homozygotes for the affected gene develop symptoms of parenchymal organ damage and especially liver cirrhosis in midlife. Early diagnosis is important in order to prevent symptoms. The protein responsible for the increased iron absorption is unknown. The tight association of the disease gene with HLA-A has been known for nearly 20 years, but its precise localization remains uncertain. Linkage and linkage disequilibrium analyses in different populations have focussed on two possible locations of the gene either very close to HLA-A, or at the telomeric site of 6p in the vicinity of the D6S105 marker.
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PMID:Hunting the hemochromatosis gene: progress and problems. 783 73

The aim of this study was to evaluate the effects of dietary iron on hepatocarcinogenesis in an animal model mimicking noncirrhotic genetic hemochromatosis. Iron overload may lead to liver cirrhosis and an increased risk of developing primary hepatocellular carcinoma. It is unknown if iron is of pathogenic importance for the carcinogenic process, or whether the increased cancer risk results solely from the cirrhotic process. We investigated the initiating, promoting, and mitogenic properties of carbonyl iron in the Solt-Farber model of chemical hepatocarcinogenesis. A diet supplemented with 2.5% to 3.0% carbonyl iron was either added to, or replaced, the initiating and promoting events in the model. None of the animals developed hepatic fibrosis. Hepatic iron was increased 6- to 13-fold in iron-treated animals, and predominantly located in periportal hepatocytes. Iron as an initiator did not increase the number of glutathione-S-transferase-Yp-positive foci. Iron reduced the number of foci when added to low-dose diethylnitrosamine plus partial hepatectomy, which may be explained by a delayed hepatic regeneration in iron-loaded liver. As a promoter, iron did not selectively induce proliferation of initiated cells. Added to a complete promotive regimen, iron decreased the volume density of preneoplastic nodules, possibly because of a mitostimulatory effect of iron on normal hepatocytes surrounding the nodules. Iron increased the hepatocyte labeling index and counteracted the mitoinhibitory effect of 2-acetylaminofluorene on regenerating liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of dietary iron on initiation and promotion in chemical hepatocarcinogenesis. 784 26


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