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

Iron-deficient female Wistar rats were fed a diet, which contained 0.5% trimethylhexanoylferrocene, over a 56-week period. This dietary iron loading resulted in a progressive siderosis and enlargement of the liver with a maximum iron content of 947.0 +/- 148.0 mg (vs. 0.07 +/- 0.04 mg in iron deficiency) and a maximum organ weight of 39.4 +/- 6.6 g (vs. 6.9 +/- 1.4 g in iron-deficient control rats). Up to 43 weeks, whole liver iron rose by increase in iron concentration (max. 28.0 +/- 6.1 mg/g wet weight, w.w.) as well as by enlargement of the organ. Afterwards whole liver iron increased solely by ongoing hepatomegaly. At the commencement of iron loading, stainable iron was almost exclusively stored by hepatocytes equally throughout all areas of the liver lobule. Later, the distribution of iron-loaded hepatocytes became strikingly periportal, and, in addition, Kupffer cells as well as sinus-lining endothelia began to store iron. Animals with a liver iron concentration of more than 10.4 +/- 0.75 mg/g w.w. showed no further increase in ferritin and haemosiderin within hepatocytes. Iron-burdened Kupffer cells/macrophages, however, accumulated permanently, hereby forming intrasinusoidal and portal siderotic nodules and areas. First signs of liver damage such as necrosis of single hepatocytes and mild fibrosis began at a liver iron concentration of 14.7 +/- 1.4 mg/g w.w. With advancement of iron loading, focal necrosis of hepatocytes and iron-burdened macrophages took place, and significant perisinusoidal as well as portal fibrosis developed. Cirrhosis, however, the final stage of impairment in iron overload of the liver in humans, could not be induced in this animal model up to now.
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PMID:Iron overload of the liver by trimethylhexanoylferrocene in rats. 159 22

Primary hemochromatosis is a genetically determined autosomal recessive disorder characterized by the excessive accumulation of body iron, most of which is deposited in the parenchymal cells of various organs. alpha 1-Antitrypsin deficiency is characterized among others by defective secretion of alpha 1-antitrypsin from liver cells. Whereas the risk of cirrhosis is increased in homozygous patients (PI ZZ) and possible in heterozygous patients (non-PI MM) as well, a greater risk for hepatocellular carcinoma has been suggested only in homozygous patients. Because these two metabolic disorders are relatively common, it has been difficult to determine whether they are associated with each other. In this study, we tried to determine the relationship between these two disorders using the case material seen at the University of Pittsburgh during a 7-yr period. We studied 15 patients with genetic hemochromatosis. alpha 1-Antitrypsin quantitation and phenotyping were performed in each case using standard methods. The distribution of the various Pi phenotypes was compared with that found in a normal population and reported elsewhere. Odds ratio and chi 2 tests were used to measure the relative risk and significance of association, respectively. Eleven patients (73%) were found to be PI M and four (27%) were identified as being heterozygotes: three (20%) were PI MZ, and one (7%) was PI MS. The prevalence of the PI MS phenotype was similar to that in the general population (7% vs. 6.4%; NS). The PI MZ phenotype, however, was statistically more common in patients with hemochromatosis than in the general population (20% vs. 2.2%; p less than 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association between heterozygous alpha 1-antitrypsin deficiency and genetic hemochromatosis. 835 11

The demonstration by CT of siderotic regenerating liver nodules in cirrhosis was evaluated and compared with that of MR imaging retrospectively in 27 patients with histologically diagnosed hepatic cirrhosis. Only in one of the two patients with marked iron deposits in regenerating nodules did CT demonstrate multiple high density nodules. In the other patient with marked iron deposits and in seven of the nine patients with moderate iron deposits, the liver parenchyma on CT was demonstrated as heterogeneous and of slightly high density without focal nodules. In 8 patients with mild to moderate iron deposits and in the 10 with no iron deposits, the liver parenchyma was homogeneous on CT. Multiple low intensity nodules in the liver were seen on fast low-angle shot (FLASH) MR images in all 17 patients with iron deposits in regenerating nodules. No low intensity nodules were seen on FLASH MR images in the 10 patients with no iron deposits. If there are iron deposits above a certain level, siderotic regenerating nodules may appear as nodules of high density on CT or as heterogeneous regions of high density liver parenchyma. Magnetic resonance is more sensitive than CT in demonstrating siderotic regenerating nodules.
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PMID:CT and MRI of siderotic regenerating nodules in hepatic cirrhosis. 162 17

Descriptions of regenerating nodules of cirrhosis indicate that they are often isointense to liver parenchyma on magnetic resonance imaging (MRI). Regenerating nodules of cirrhosis can occasionally appear hypointense on all MRI sequences due to iron deposition within the nodules. We reviewed 21 cases of pathologically proven mixed or macronodular cirrhosis using MRI. In five patients, nodules appeared as hyperintense to liver parenchyma on short TR/TE images and were isointense on long TR/TE or GRASS images. In another five cases, nodules appeared hypointense on either long TR/TE or GRASS images, and corresponding hypointense nodules were observed on short TR/TE images in one of these patients. Our findings suggest that regenerating nodules of cirrhosis may have a more variable appearance on short TR/TE images.
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PMID:Hyperintense cirrhotic nodules on MRI. 165 76

Magnetic resonance demonstrated siderotic regenerating nodules in a patient with hepatocellular carcinoma with accompanying liver cirrhosis. The siderosis disappeared when iron deficiency anemia developed in association with biliary hemorrhage. Magnetic resonance was sensitive enough to follow changes in the siderosis. The mechanism of iron deposition in regenerating nodules that accompanied liver cirrhosis did not seem to be related to the severity of the liver damage.
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PMID:Siderotic nodules in hepatic cirrhosis disappearing after biliary hemorrhage: MR imaging. 165 91

Several data indicate that iron may be involved in the pathogenesis of hepatocellular carcinoma (HCC). A high prevalence of HCC has been reported in patients with genetic hemochromatosis and the risk of HCC appears to be related to the amount and duration of iron overload. Iron, which has been demonstrated to facilitate persistent hepatitis B or C infection, could also act as a co-factor in the pathogenesis of HCC in patients with hepatitis B or C. Among the possible mechanisms by which iron could exert its cancerogenetic potential, free radicals production responsible for heritable genetic alterations appears to be one of the most important, although the fibrogenetic capability of iron, potentially leading to cirrhosis, cannot be underestimated.
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PMID:Iron in the pathogenesis of hepatocellular carcinoma. 166 94

Genetic haemochromatosis is characterised by an inappropriately high rate of iron absorption by the small intestine. The disease is transmitted as an autosomal recessive condition. The gene frequency in the Caucasian population is approximately 1 in 20 and the disease frequency is 1 in 400. Excessive iron deposition occurs in the liver, pancreas, heart, pituitary and joints and hepatic iron concentrations above approximately 400 mumol/g dry weight are always associated with fibrosis and usually with cirrhosis and progressive liver failure. Accurate diagnosis depends upon the demonstration of elevated hepatic iron stores. An hepatic iron index [hepatic iron concentration (in mumol/g dry weight) divided by patient age] of greater than 2.0 distinguishes homozygous subjects from the other conditions in which slight increases in hepatic iron concentration may occur, e.g. in a subject heterozygous for haemochromatosis or alcoholic liver disease. If cirrhosis is present, patients are at a high risk of developing hepatocellular carcinoma. Therefore, they should undergo regular abdominal ultrasound and alpha-fetoprotein estimation. In the absence of cirrhosis, phlebotomy restores life expectancy to normal. Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years). If serum ferritin or transferrin saturation are abnormal, liver biopsy should be undertaken. HLA typing of the family allows for the identification of those siblings who are most likely to develop the disease. Secondary iron overload is often multifactorial in origin. Iron chelation therapy with subcutaneous deferoxamine (desferrioxamine) should only commence after careful consideration of the potential benefits in each individual patient.
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PMID:Current concepts in rational therapy for haemochromatosis. 171 64

Hereditary haemochromatosis is a recessive disease in which primary hepatocellular carcinoma, complicating cirrhosis, is responsible for about one-third of deaths in affected homozygotes. We describe a unique HLA haplo-identical pedigree showing parent-to-offspring transmission of hereditary haemochromatosis in whom HLA typing studies, including class I and class II allogenotype analysis, were of no benefit in identifying affected homozygotes. However, affected siblings in the pre-cirrhotic stage of haemochromatosis, with apparent discordance between the haemochromatosis allele and class I loci on chromosome 6, were detected by undertaking a family study, using analysis of serum parameters of iron status in combination with magnetic resonance imaging (MRI). This pedigree emphasises the critical importance of genetic and non-invasive methods for the identification of asymptomatic homozygotes before cirrhosis develops.
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PMID:Detection of hereditary haemochromatosis in an HLA-identical pedigree showing discordance between HLA class I genes and the disease locus. 175 96

Eight patients with hemochromatosis (HC) were followed up. For a long time HC ran a latent course. Throughout many years, the symptoms occurred at varying succession. In many cases, the first manifest symptoms included skin itch, arthropathy, and diabetes mellitus. They may be dominant in the clinical picture for a long time, masking the genuine cause of the disease. The correct diagnosis was established, as a rule, at the pronounced stage of HC. Before that event the patients were followed up and treated by the endocrinologist (3 persons), by the infectionist (2 persons), dermatologist and traumatologist (2 persons), and by the internist (1 person). Appearance of one of the symptoms of the classical triad can be regarded as the onset of HC. The cardinal symptoms that determine the clinical picture progressed for the most part: liver cirrhosis, diabetes mellitus, and melanoderma. The first two require appropriate correction. Melanoderma presents a cosmetic and social and psychological problem. In HC patients, disorders occurring by the type of liver porphyria are recordable. They are of secondary nature, being an unfavourable prognostic sign. Investigation of iron metabolism in patients suffering from chronic liver diseases should be carried out by all means, since it can be regarded a specific enough test in the diagnosis of HC. Emphasis is laid on the importance of early diagnosis of HC.
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PMID:[The clinical characteristics of the course of hemochromatosis]. 178 14

What then are the lessons to be learned about prevention and treatment of hemochromatosis? Early diagnosis is essential. The best indicator would be testing of serum iron and total saturation followed by a serum ferritin if elevated. Once these indices are abnormally high, MRI and or a liver biopsy should confirm the stage of the iron over-loaded state. If indeed the patient is not iron-overloaded (normal liver biopsy in the face of high saturation and ferritin level) phlebotomies should be performed until these indices are normal and then maintained at a normal level. This should entail four to six phlebotomies a year. Family members should also be screened and managed in a like manner. HLA typing may be a partially helpful screening device. The abnormal gene is closely linked on chromosome 6 with HLA histocompatibility loci. Now, by means of HLA typing, we can identify heterozygote carriers and homozygous (abnormal) among first degree relatives of patients with hemochromatosis. Unfortunately, HLA typing can only be used within a given family and cannot be used to screen the general population. It is estimated that 70% of hemochromatoics have the antigen HLA-A3; however, so does 28% of the (well) general population. Patients with unexplained cirrhosis, arthritis, liver disease, diabetes, impotency, cardiomyopathy and neurological symptoms should be screened in a like manner. Routine health practice profile chemistries must include a serum iron and iron saturation, and if high followed by a serum ferritin. Once diagnosed, therapy must be maintained with phlebotomy for the life time of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemochromatosis: diagnosis and treatment. 179 61


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