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

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

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder that can result in iron overload and a wide range of clinical complications, including hepatic cirrhosis, diabetes mellitus, hypopituitarism, hypogonadism, arthritis, and cardiomyopathy. People with HH can be detected at an asymptomatic stage of the disease by abnormalities in serum iron measures. Early detection is desirable, because periodic phlebotomy provides effective treatment for iron overload and may prevent complications of the disorder. The natural history of HH is poorly understood, however, and the proportion of people detected by screening who will develop serious complications of HH is unknown. The genetics of HH may help to resolve these questions. The gene, HFE, and two mutations, C282Y and H63D, have been identified: the C282Y mutation has a higher penetrance than the H63D mutation, and appears to result in a greater loss of HFE protein function. Most people with HH are C282Y homozygotes, a small proportion are compound heterozygotes or H63D homozygotes, and some have no identifiable HFE mutation or are HFE heterozygotes, suggesting that additional mutations associated with HH are yet to be found. Gender and environmental agents, such as alcohol and dietary iron, influence phenotypic expression of HH. The severity of HH is thus determined by an interaction between genotype and modifying factors. HFE mutations also appear to increase the likelihood of iron overload in inherited anemias and to promote the clinical manifestations of porphyria cutanea tarda. HH is an important paradigm for medical genetics because it offers an opportunity to explore the complexity of gene gene and gene environment interactions.
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PMID:Hemochromatosis: genetics helps to define a multifactorial disease. 972 31

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

A case of hereditary hemochromatosis in a patient affected by anti-HCV positive liver cirrhosis is described. The difficulties for an exact diagnosis are underlined. Really, it can be particularly difficult to make a differential diagnosis between hereditary hemochromatosis and secondary hemochromatosis, if liver cirrhosis has already been found. Practically, at this stage of disease, the histological and clinical aspects of these two forms become completely interchangeable. Moreover, diagnostic difficulties increase when, at the same time, the patient presents more causes of potential liver damage. In this case report, the DNA-analysis, obtained by polymerase chain reaction amplification and enzymatic digestion, allows to make the diagnosis of hereditary hemochromatosis, because it showed the presence of two genetic mutations, considered responsible for the disease. Both the hereditary hemochromatosis and the HCV infection, had greatly contributed to the development of liver cirrhosis. In the future, DNA-analysis by amplification with polymerase chain reaction, can assume relevant importance for the screening of affected patients' first grade parents too. It could permit an early diagnosis of hereditary hemochromatosis and then to start a timelier and more efficacious therapy, to prevent an irreversible histological damage.
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PMID:[Diagnosis of hereditary hemochromatosis with molecular analysis of DNA in patients with anti-HCV positive liver cirrhosis. Clinical case]. 985 21

A case of a 62-year-old patient with hereditary hemochromatosis is reported, who developed hepatocellular carcinoma (HCC) in the absence of cirrhosis and other potential risk factors for HCC. Occurrence of HCC in patients with genetic hemochromatosis and noncirrhotic liver is a rare event which has previously been described only six times and appears to be limited to male patients.
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PMID:Hepatocellular carcinoma in a patient with hereditary hemochromatosis and noncirrhotic liver. A case report. 1044 68

Hereditary hemochromatosis (HHC) is the most common inherited single gene disorder in people of northern European descent. Hereditary hemochromatosis is characterized by increased intestinal absorption of iron leading to its deposition into multiple organs. The classic description of HHC is bronze diabetes in a patient with cirrhosis. Hereditary hemochromatosis is increasingly being diagnosed at an earlier, less symptomatic stage. Diagnosis is based on an elevated fasting early morning transferrin saturation. Treatment is by phlebotomy, which, if initiated before the development of cirrhosis or diabetes, is associated with a normal life expectancy. Recently, a gene associated with HHC was discovered and named HFE. Two point mutations of this gene have been referred to as C282Y and H63D. Several US and European studies have found that 60% to 93% of patients with suspected HHC are homozygous for C282Y. Positive results of HFE gene testing may eliminate the need for a liver biopsy in selected cases. The greatest utility of HFE gene testing will likely be in screening family members of an identified proband and in helping to resolve ambiguous cases.
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PMID:Update on hereditary hemochromatosis and the HFE gene. 1048 96

Universal screening for hereditary hemochromatosis (HH) has been proposed by many experts, with understandable enthusiasm: HH can cause fatal complications, which are preventable with early treatment. The disorder involves excess iron accumulation that can result in tissue iron overload, with secondary cirrhosis, diabetes, heart failure, impotence and arthritis. These complications are preceded by years of iron accumulation, and most are believed to be preventable by removal of excess iron by phlebotomy. Thus, early identification and treatment - the quintessential functions of health screening - seem to make sense for HH. However, the available screening tests are imperfect. While they can identify many persons at increased risk from HH, the proportion that will develop serious clinical manifestations related to iron overload is not known with certainty. DNA-based tests do not provide a simple resolution to these questions.
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PMID:Screening for hereditary hemochromatosis: are DNA-based tests the answer? 1049 10

The iron content of the body is normally tightly controlled by regulation of iron absorption. In hereditary hemochromatosis, mutation of an HLA class 1 gene, designated HFE, results in excessive iron absorption. Over many years, accumulating iron produces tissue damage, most notably cirrhosis, cardiomyopathy, diabetes, and arthropathies. Hereditary hemochromatosis is the most common hereditary disease of Northern Europeans with a prevalence of approximately 5 per 1000. The most sensitive screening test for hemochromatosis is saturation of the transferrin with iron; a fasting value greater than 50% is strongly suggestive of the disease. Confirmation of increased iron storage can be achieved most readily by serial phlebotomy. We do not regard liver biopsy to be indicated, except in unusual circumstances. Early diagnosis and treatment by phlebotomy before tissue damage has occurred is essential, because life span seems to be normal in treated patients but markedly shortened in those who are not. Therefore, genetic counseling with evaluation of first-degree relatives is mandatory.
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PMID:New developments in hereditary hemochromatosis. 1052 53


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