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

Hemochromatosis is a syndrome which, when fully expressed, is manifested by melanoderma , diabetes mellitus, and liver cirrhosis, with iron overload involving parenchymal and reticuloendothelial cells in many organ systems. This clinical presentation may arise as a consequence of either hereditary or acquired abnormalities of iron overload, although the mechanisms are quite different. In hereditary hemochromatosis (also known as primary, or idiopathic, hemochromatosis), increased intestinal iron absorption leads to excessive accumulations of iron, throughout the body, particularly in parenchymal cells. In secondary forms of iron overload including transfusional hemosiderosis, alcoholic cirrhosis, thalassemia, sideroblastic anemia, and porphyria cutanea tarda, iron accumulates in the reticuloendothelial system initially, but with increasing amounts of total body iron, excessive iron deposits eventually accumulate in parenchymal cells throughout the body producing a picture indistinguishable from hereditary hemochromatosis. In this article, the course, prognosis, and therapy of iron overload will be reviewed in detail. Clinical and experimental data concerning the pathogenesis of the different forms of iron overload will be examined critically. In particular, information relating to possible abnormalities of reticuloendothelial function, intestinal mucosal iron transport, and alterations in serum and tissue isoferritin patterns in hereditary hemochromatosis will be analyzed, and possible directions for future research will be suggested. The mode of inheritance and linkage with the major histocompatibility (HLA) complex will be discussed. Theories on the pathogenesis of tissue damage by excess iron will be evaluated. Methods for measuring the extent of iron overload in clinical practice will be described, including measurements of serum iron, serum ferritin, iron absorption, cobalt excretion, desferrioxamine excretion, liver biopsy and tissue iron determinations, and HLA typing. Finally, unresolved problems in the understanding of the disease process, diagnosis, and therapy will be delineated.
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PMID:Iron overload disorders: natural history, pathogenesis, diagnosis, and therapy. 637 41

Idiopathic hemochromatosis (IHC) is a genetically determined impairment in control of iron absorption that results in excessive parenchymal iron deposition, particularly in the liver. Of patients with IHC, 50% have little or no chemical evidence of liver dysfunction. Cirrhosis may be clinically occult, but still cause a syndrome of chronic hepatocerebral degeneration. Two patients are reported with IHC and a syndrome of ataxia, rigidity, myoclonic jerks, and dementia. Other associated symptoms may include diminished libido, decreased hearing, peripheral neuropathy, and large joint disease. Because symptoms of IHC can be reversed by phlebotomy, appropriate laboratory studies should be considered to exclude IHC in any patient with unexplained dementia, encephalopathy, and gait ataxia.
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PMID:Idiopathic hemochromatosis (IHC): dementia and ataxia as presenting signs. 668 41

Although hereditary hemochromatosis is an autosomal recessive disease, most homozygotes are concerned with the genetic implications for their children. The optimal age for testing children and the cost implications of screening their children have not been clearly established. A clinical database consisting of 255 children from families with at least one homozygote is used to assess the prevalence of homozygotes among children of homozygous parents and to review the biochemical abnormalities and life-threatening symptoms in these young adults. Decision analysis is used to estimate the cost and utility of screening children of a homozygous parent. Eleven homozygotes were discovered among children of homozygotes. Only one male had a life-threatening event, cirrhosis. Decision analysis estimated cost saving of $12 per child screened ($ net present value) and a saving of 10 quality-adjusted days per child screened at age 10 years compared with not screening. If screening began at age 20 years, there is a cost saving of $65 per child screened. Sensitivity analysis showed that the major factors influencing cost savings were the cost of venesections, sensitivity and specificity of the screening tests, and prevalence of disease. Because the prevalence of hemochromatosis is higher in children of homozygotes than in the general population, screening with transferrin saturation and ferritin as early as age 10 years is recommended. Savings are augmented if the cost per venesection is eliminated by allowing hemochromatosis patients to become voluntary blood donors.
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PMID:Screening for hemochromatosis in children of homozygotes: prevalence and cost-effectiveness. 748 80

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

Hereditary hemochromatosis is a common disorder of iron metabolism with a prevalence as high as 8 per 1000. Affected individuals absorb excessive amounts of dietary iron and over time, tissue iron deposition results in skin discoloration, arthropathy, hepatic cirrhosis, heart failure, diabetes mellitus and impotence. Early diagnosis and institution of phlebotomy treatments will prevent these manifestations and normalize life expectancy. Once organ damage is established many of the manifestations are irreversible. Since the early manifestations of the disease are subtle, a case can be made for routine screening. This conclusion is supported by cost-effectiveness analysis based on available data. A reasonable screening strategy would start with a serum transferrin saturation. A value > or = 55% should trigger a repeat transferrin saturation in a fasting state and a serum ferritin level. If both these tests are abnormal, a liver biopsy with quantitative iron determination is the currently accepted confirmatory test.
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PMID:Management of hereditary hemochromatosis. 788 27

Hereditary hemochromatosis is a prevalent inherited disorder with an estimated frequency of homozygosity of 0.2 to 0.45% in Caucasians. The disease is characterized by progressive iron overload until a massive accumulation of body iron occurs. Undetected, the disorder eventually can produce either cirrhosis, diabetes mellitus, cardiac disease, arthritis, or hepatocellular carcinoma or a combination of these manifestations. Early diagnosis and treatment prevents organ damage and normalizes life expectancy. Screening studies to detect hemochromatosis are most effectively accomplished by measurement of the serum iron and total iron binding capacity. Treatment is most effectively performed by frequent phlebotomy until body stores are empty and then 3 to 4 times yearly for life. The basic defect of hemochromatosis appears to increase iron absorption, decrease iron excretion, and produce preferential deposit of iron in hepatic parenchymal cells rather than Kupffer cells. The genetic abnormality of hemochromatosis is located on chromosome 6 in close association with the gene for HLA antigens. Recent speculation postulates that tumor necrosis factor may be involved in the etiology of this disease because of its location on chromosome 6 and its effect upon iron transport.
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PMID:Hereditary hemochromatosis: a prevalent disorder of iron metabolism with an elusive etiology. 794 87

The relationship between alcoholism and hereditary hemochromatosis remains controversial. Previous studies have included patients with alcoholic siderosis rather than hereditary hemochromatosis. In this retrospective study, the clinical features, iron status, alcohol history, liver histology, and long-term survival were reviewed in 105 homozygotes for hemochromatosis using rigid diagnostic criteria including an HLA identical sibling with iron overload. Heavy alcohol consumption (>80 g ethanol/day) was found in 15 percent of hemochromatosis patients. Histological features of alcoholic liver disease (Mallory's hyaline bodies, pericentral fibrosis, polymorphonuclear infiltrate, and fatty infiltration) were uncommon in hemochromatosis. Hemochromatosis patients with heavy alcohol consumption had a higher prevalence of cirrhosis than hemochromatosis patients without heavy alcohol consumption. Hepatic iron concentration and hepatic iron index did not significantly differ between these two hemochromatosis groups. Long-term survival was significantly reduced in patients with heavy alcohol consumption (mean follow-up, 9.22 years). This suggests that chronic alcohol consumption has an additive hepatotoxic effect despite the paucity of histological features of alcoholic liver disease.
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PMID:Alcoholism in hereditary hemochromatosis revisited: prevalence and clinical consequences among homozygous siblings. 866 24

Hepatic parenchymal iron deposition is a well-known complication of chronic hepatic inflammatory states. This can make the differential between chronic hepatitis and hereditary hemochromatosis difficult, however. The case of a 13-yr-old male with chronic hepatitis C and hereditary hemochromatosis resulting in end stage liver disease and the need for orthotopic liver transplantation is described. There has been no previously described case of the coexistence of these two diseases in a pediatric patient, resulting in end stage liver disease. The progression to cirrhosis in a patient of this age suggests a more rapid progression of the combined diseases than with either disease alone.
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PMID:End stage liver disease in a 13-year old secondary to hepatitis C and hemochromatosis. 867 8

Approximately 1.5 million persons in the United States are affected by iron overload diseases, which are primarily caused by hereditary hemochromatosis--the most common genetic disorder in the United States. Hereditary hemochromatosis is characterized by increased iron absorption in the gastrointestinal tract, which may cause lifelong excessive iron absorption and accumulation and serious health effects, including arthritis, cirrhosis, diabetes, impotence, heart failure, and death. Hereditary hemochromatosis is an autosomal recessive disease; the estimated prevalence of the homozygous genotype is 1:200 - 1:250 persons, and 10% of persons are carriers. Although the disease was previously believed to affect primarily white males of northern European descent, recent data indicate hereditary hemochromatosis also occurs among blacks. Moreover, iron overload diseases are underdiagnosed among whites and may not be considered in other racial/ethnic groups (e.g., Hispanics) even when compatible symptoms and clinical findings are present. As part of a joint demonstration project during August-October 1995 to determine the overall prevalence of iron overload, CDC reviewed data from a health-maintenance organization (HMO) in San Diego, California; the prevalence among Hispanics appeared similar to that for non-Hispanic whites. This report presents the preliminary findings of an analysis of the prevalence of iron overload among Hispanics and compares these findings with nationally representative data from the Third National Health and Nutrition Examination Survey (NHANES III). These findings indicate that the prevalence of possible iron overload among Hispanic clients of the HMO based on initial screening was consistent with the nationwide prevalence of possible iron overload based on a single screening test for Hispanics of Mexican descent and non-Hispanic whites.
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PMID:Iron overload disorders among Hispanics--San Diego, California, 1995. 900 7

Hereditary hemochromatosis (HHC) is an inherited disease transmitted in an autosomal recessive pattern. With homozygosity occurring in up to 0.5% of the population, HHC is the most prevalent genetic disease among the white population worldwide and has the same prevalence as the sickle cell trait in the African-American population. An asymptomatic 50-year-old white man presented at the family practice clinic and stated that HHC had been diagnosed in his mother. Laboratory findings showed markedly elevated transferrin saturation and ferritin levels. The diagnosis of HHC was made on the basis of the laboratory results and family history, and therapy was begun. Clinical manifestations of HHC occur late and include diabetes mellitus, cirrhosis, and cardiomyopathy. As end-organ damage is preventable, optimal management involves early diagnosis and lifelong phlebotomy. Diagnosis is made by an elevated transferrin saturation level and an increased serum ferritin value. Hereditary hemochromatosis is a genetic disorder of iron metabolism that has an excellent prognosis if diagnosed early.
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PMID:Hereditary hemochromatosis. 907 Dec 52


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