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)

Under normal conditions, vitamin D absorbed from the diet or synthesized in the skin is transported to the liver where it undergoes hydroxylation. The purpose of this study was to determine whether excess hepatic iron affects this process and the subsequent production of 1,25-dihydroxyvitamin D (1,25-[OH]2D) in the kidney. Mean serum 25-hydroxyvitamin D (25-OHD) concentrations in untreated hereditary hemochromatosis were 13 +/- 6 (SD) in 9 patients with cirrhosis, 13 +/- 6 in 5 patients with hepatic fibrosis, and 22 +/- 6 in 10 patients with normal hepatic architecture aside from siderosis and were significantly lower than the levels found in 24 controls matched for age, sex, and season, p less than 0.05. The mean serum 25-OHD levels in the two groups with hemochromatosis and hepatic damage were significantly lower than the value in the group with normal hepatic architecture, p less than 0.05. Serum 25-OHD levels in individual patients were inversely related to the size of body iron stores as measured by exchangeable body iron, r = -0.64, or serum ferritin, r = -0.47, p less than 0.05. In 15 patients removal of excess body iron by venesection therapy produced a significant increase in the mean serum 25-OHD from 20 ng/ml to 30 ng/ml, p less than 0.05. In contrast, mean serum 1,25-[OH]2D levels were similar in iron-loaded and control subjects, indicating that the regulation of this metabolite was intact in patients with hemochromatosis. The results reveal that the low serum 25-OHD concentration in patients with hemochromatosis is directly related to the extent of iron loading and it is improved by venesection therapy.
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PMID:Low serum 25-hydroxyvitamin D in hereditary hemochromatosis: relation to iron status. 383 88

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

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

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

Our objective was to study the predictive value of the family history in the initial diagnosis of hereditary hemochromatosis. Sixty five hemochromatosis proband patients and 66 control patients with chronic liver disease were assessed for a family history of hemochromatosis, cirrhosis, diabetes, and arthritis. There were no significant differences in the frequency of cirrhosis, diabetes, and arthritis between hemochromatosis patients and control patients. A family history of hemochromatosis was present in 3.6% of hemochromatosis patients and none of the control patients. Multivariate discriminative analysis demonstrated that the combination of cirrhosis, diabetes, and arthritis could only predict the diagnosis of hemochromatosis in 48% of cases. We conclude that a family history of cirrhosis, arthritis, and diabetes is not more common in hemochromatosis patients compared to control patients with chronic liver disease.
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PMID:Predictive value of family history in diagnosis of hereditary hemochromatosis. 920 Nov

Among patients with hepatic iron overload, the distinction between hereditary hemochromatosis (HH), a common yet treatable genetic disease, and other causes of siderosis remains problematic. The recent discovery of a specific homozygous mutation (C282Y) in a novel major histocompatibility complex class I-like gene (named HLA-H or HFE) in 80% to 100% of well-characterized cases of HH suggests that direct DNA-based mutation analysis may help resolve this dilemma. To assess the clinical utility of direct HLA-H mutation analysis in a typical diagnostic setting, we measured genotypic and phenotypic parameters of iron overload in 37 subjects with biopsy-proven hepatic siderosis (2+ or greater) and in 127 healthy control subjects. The prevalence of C282Y homozygotes was significantly greater in the hepatic siderosis group (32%) than in the control group (0%), confirming the association between this homozygous mutation and hepatic iron overload. In the hepatic siderosis group, C282Y homozygotes had significantly higher hepatic iron and ferritin levels, a significantly lower prevalence of hepatitis C virus or alcoholic liver disease, but no significant difference in the saturation of serum transferrin. Of the 20 subjects with a hepatic iron index (HII) in the previously defined "hemochromatosis range" (>1.9), 9 (45%) were C282Y homozygotes. Of the 11 nonhomozygous subjects with an HII greater than 1.9 (presumed false-positive HIIs), 10 (91%) had hepatic cirrhosis compared with 3 of 9 (33%) homozygotes with an HII greater than 1.9 who had cirrhosis (P<.02). The HII thus has poor diagnostic specificity for predicting genotypic HH in patients with cirrhosis. We conclude that direct determination of the HLA-H C282Y genotype may be the single best diagnostic test for HH, particularly in patients with cirrhosis, for whom the HII is quite nonspecific.
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PMID:Hepatic iron overload: direct HFE (HLA-H) mutation analysis vs quantitative iron assays for the diagnosis of hereditary hemochromatosis. 957 64

Hepatic iron has been associated with more aggressive liver disease in chronic viral hepatitis. We evaluated whether the recently described C282Y mutation of the hemochromatosis gene, designated HFE (responsible for at least 83% of hereditary hemochromatosis), was associated with more advanced liver disease in chronic hepatitis C. One hundred thirty-seven patients with biopsy-proven chronic hepatitis C were studied and liver biopsies scored for necroinflammation (grade 0-18) and fibrosis (stage 0-6). Genomic DNA was amplified by polymerase chain reaction and the C282Y mutation identified by restriction with RsaI and electrophoretic separation of restriction fragments. Ten (7.3%) patients had the C282Y mutation. No C282Y homozygous patients were identified. Age, sex distribution, and estimated weekly alcohol consumption were not significantly different between those with and without the mutation. Serum ferritin was higher in the heterozygotes (mean, 339 microg/L) compared with homozygous wild types (153 microg/L; P = .0005). In the majority of patients, liver iron was graded 0 out of 4, but hepatocyte iron staining was more commonly present in heterozygotes compared with homozygous normals (30% compared with 4% [P = .02]). Liver disease was more advanced in those with the mutant allele (mean fibrosis stage: 3.6, compared with wild type: 1.5 [P = .01]). Cirrhosis was found more often in those with the mutation (40%) compared with those without (8.7%) (P = .01; odds ratio: 7.6 [1.9-31.2]). There was no significant difference in inflammation scores between heterozygotes and wild type (mean, 5.4 compared with 4.1). Hepatitis C virus (HCV)-RNA titers were measured by branched DNA assay (HCV RNA 2.0-Chiron), and there was no difference between heterozygous and homozygous normal patients. Thus, despite relatively minor increases in iron stores, individuals who are heterozygous for hemochromatosis appear to develop more fibrosis in chronic hepatitis C. Venesection may be useful therapy in this subgroup.
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PMID:Heterozygosity for hereditary hemochromatosis is associated with more fibrosis in chronic hepatitis C. 1033 38

A middle-aged white man of Scotch-Irish ancestry, being treated for chronic hepatitis C, was found to be heterozygous for alpha1-antitrypsin deficiency (PiMZ phenotype) after diagnostic PAS-positive, diastase-resistant globules were detected in a liver biopsy. The globules had not been present in a biopsy obtained 4 yr previously. He was also found to be heterozygous for the cys282tyr mutation of the HFE gene, which is the chief cause of HLA-linked hereditary hemochromatosis (HHC). His liver disease progressed over 4 yr from mild hepatitis to moderate hepatitis with cirrhosis despite therapy with interferon-alpha, and phlebotomy plus interferon. These conditions appeared to have synergistic effects, with the chronic viral hepatitis unmasking the alpha1AT deficiency, and the alpha1AT deficiency (and possibly the heterozygosity for HHC), exacerbating the course of the hepatitis C.
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PMID:Enhanced phenotypic expression of alpha-1-antitrypsin deficiency in an MZ heterozygote with chronic hepatitis C. 973 41


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