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)

Hepatocellular carcinoma in patients with hereditary hemochromatosis in the cirrhotic phase is one of the complications causing greatest mortality and may present in spite of removal of excess iron by bloodletting. Hepatocellular carcinoma is usually considered to occur in cirrhotic livers and consequently measures for the early diagnosis of this complication are only recommended in this type of patient. We present the case of a 69-year-old female patient with non-cirrhotic hemochromatosis who, 6 years after undergoing successful treatment, developed hepatocellular carcinoma. This observation should be added to the 12 cases published in the literature. Criteria should be established for the early diagnosis of hepatocellular carcinoma in patients with hereditary hemochromatosis, irrespective of whether they have cirrhosis.
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PMID:[Hepatocellular carcinoma in a patient with hereditary hemochromatosis without cirrhosis]. 1126 Dec 25

Severe iron overload usually develops in patients with hereditary hemochromatosis (HHC), but variability in the phenotypic expression of the disease has been reported. This study assessed whether tumor necrosis factor alpha (TNF-alpha) plays a role in phenotypic expression of HHC. Sixty-four patients with HHC and 172 healthy volunteers (controls) were studied. Release of TNF-alpha from stimulated peripheral blood monocytes was measured by enzyme-linked immunosorbent assay, and 308 and 238 TNF-alpha polymorphisms were detected with polymerase chain reaction and restriction fragment-length polymorphism analysis. The relation between TNF-alpha polymorphisms and clinical expression of HHC was evaluated. Patients with HHC released less TNF-alpha than controls, but the difference was significant only in homozygotes for the C282Y mutation. The prevalence of the 308 TNF-alpha polymorphism was similar in patients and controls, whereas the prevalence of the 238 polymorphic allele was significantly lower in patients (3% versus 16%; P =.002). A lower prevalence of cirrhosis was observed in patients with TNF-alpha polymorphism than in those without it (4 of 15 [27%] versus 28 of 49 [57%]), but the difference was not significant (P =.07). In nonhomozygotes for the C282Y mutation, severe liver siderosis was less prevalent in patients with the 308 polymorphism than in those without it (P =.05). Alanine aminotransferase (ALT) values were significantly lower in patients with TNF-alpha polymorphism (P =.006), even when patients with other hepatotoxic factors were excluded. Multivariate analysis showed that TNF-alpha polymorphism was independently associated with ALT values (P =.0008 and P =.045, respectively, in homozygotes and nonhomozygotes for the C282Y mutation) and siderosis in nonhomozygotes (P =.047). Thus, TNF-alpha appears to play a role in HHC by modulating the severity of liver damage. (Blood. 2001;97:3707-3712)
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PMID:Tumor necrosis factor alpha promoter polymorphisms influence the phenotypic expression of hereditary hemochromatosis. 1138 6

During the last decades efforts regarding dietary iron supply focused mostly on the prevention of deficiencies, especially during growth and pregnancy. Correspondingly, homeostatic mechanisms increase intestinal iron absorption in iron deficiency, but its downregulation at high intake levels seems insufficient to prevent accumulation of high iron stores at high intake. There is no regulated iron excretion in overload. Excess of pharmaceutical iron may cause toxicity and therapeutic doses may cause gastrointestinal side effects. Chronic iron excess, e.g. in primary and secondary hemochromatosis, may lead to hepatic fibrosis, diabetes mellitus and cardiac failure. Chronic intake of 50-100 mg Fe/day of highly bioavailable iron with home-brewed beer in sub-Saharan Africans lead to cirrhosis and diabetes. Applying a safety factor of 2 would lead to an upper safe level of 25-50 mg Fe/day for this endpoint of conventional iron toxicity. However, beyond this kind of damage iron is known to catalyze the generation of hydroxyl radicals from superoxide anions and to increase oxidative stress which, in turn, increases free iron concentration. This self-amplifying process may cause damage to lipid membranes and proteins, which relates radical generation and organ damage after ischemia-reperfusion events to available free iron in clinical and experimental settings. Correspondingly, epidemiological studies as well as observations in heterozygotes for hereditary hemochromatosis suggest that the risk of atherosclerosis and acute myocardial infarction is related to body iron stores, though there is conflicting epidemiological evidence as well. The most recent and best controlled studies, however, support the hypothesis that iron stores are related to cardiovascular risk. Iron-amplified oxidative stress may also increase DNA damage, oxidative activation of precancerogens and support tumor cell growth. This is supported by experimental, clinical and epidemiological observations. Due to these mechanisms high iron stores may present a health hazard. Though this has not been finally proven, available evidence strongly recommends not to increase iron intake beyond physiological requirements. To avoid iron deficiency symptoms, on the other hand, care must be taken to meet recommended daily intake.
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PMID:Safety aspects of iron in food. 1142

Vibrio vulnificus is an extremely invasive gram-negative bacillus found in marine waters that causes overwhelming bacteremia and shock that is associated with high mortality. Impaired iron metabolism has been implicated in the susceptibility to V vulnificus bacterial infections. We report a case of fatal V vulnificus sepsis in a 56-year-old man who died within 1 to 3 days after consuming raw seafood. At autopsy, he was found to have micronodular cirrhosis and iron overload. Postmortem genetic analysis revealed the presence of the hemochromatosis gene (HFE) C282Y mutation. To our knowledge, this is this first documented fatal case of V vulnificus infection in a patient proven to carry the HFE C282Y mutation. Because this patient was heterozygous for the major hereditary hemochromatosis mutation and was not previously diagnosed with clinical iron overload, the spectrum of clinical susceptibilities to V vulnificus infection may include carriers of the C282Y mutation.
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PMID:Vibrio vulnificus septicemia in a patient with the hemochromatosis HFE C282Y mutation. 1147 71

The possible role of iron in facilitating the development of liver cancer is still debated. The aims of this study were to define the prevalence of the mutations 845G --> A and 187C --> G (C282Y and H63D) in the HFE gene associated with hereditary hemochromatosis in Italian patients with hepatocellular carcinoma occurring in cirrhosis and to analyze the interaction between these mutations and other established risk factors for hepatocellular carcinoma. The HFE gene mutations, performed by polymerase chain reaction, were analyzed in 81 patients (63 males, 18 females) with hepatocellular carcinoma. None of the patients had a phenotype compatible with homozygous hereditary hemochromatosis. Interaction between HFE mutations and exogenous risk factors was analyzed by collecting information on alcohol consumption, hepatitis B and C virus infections, and iron status at the time of diagnosis of chronic liver disease. This analysis was performed only in males to rule out gender influence on patients' iron status by using the case-only approach specifically designed to estimate departure from multiplicative risk ratios under the assumption of independence between genotype and environmental exposure. The prevalence of the C282Y mutation was significantly higher in patients with hepatocellular carcinoma than in normal controls (8.6% vs 1.6%, P < 0.03). At univariate analysis, iron overload was significantly associated with both HFE mutations (P < 0.0001), whereas ongoing hepatitis B virus infection was associated with the C282Y mutation (P < 0.05). By multivariate analysis, a trend for an increased risk of being positive for hepatitis virus markers (OR 2.9, CI 95% 0.9-9.5) and of having been alcohol abusers (OR 3, CI 95% 0.7-14) was observed in patients heterozygous for the HFE mutations. These data indicate that the prevalence of the main mutation associated with hereditary hemochromatosis is significantly higher in cirrhotic Italian patients with hepatocellular carcinoma compared to a normal population and suggest that heterozygotes for HFE mutations exposed to hepatitis virus infections or who had been alcohol abusers could have an increased risk of developing cirrhosis and later liver cancer than people without the mutations exposed to the same risk factors.
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PMID:Mutations in the HFE gene and their interaction with exogenous risk factors in hepatocellular carcinoma. 1150 61

Early erroneous diagnosis of rheumatic disease is common in subjects with arthropathy due to hereditary hemochromatosis. A 71-year-old male with chronic obstructive pulmonary disease and monoclonal gammopathy underwent hip replacement and was referred to our Department because of altered liver function tests. Test results were negative for hepatitis B surface antigen and hepatitis C virus, and positive for rheumatoid factor. A diagnosis of rheumatoid arthritis had been made on the basis of compatible joint involvement and laboratory data and steroid treatment prescribed. Since his serum ferritin was 3249 ng/mL, genetic testing for hereditary hemochromatosis was carried out and revealed homozygosity for Cys282Tyr mutation in the HFE gene. Liver biopsy disclosed cirrhosis compatible with hemochromatosis. Following a review of the patients' radiographs, the diagnosis of hemochromatosis arthropathy was made. Phlebotomies and family screening for hereditary hemochromatosis were done. The most logical explanation for the positive rheumatoid factor result in this subject are his age and the presence of two chronic diseases involving long-standing antigenic stimulation and monoclonal gammopathy of uncertain significance. It is important to distinguish rheumatoid arthritis from hemochromatosis arthropathy for several reasons: patients with hereditary hemochromatosis do not require corticosteroid treatment; in case of erroneous diagnosis of rheumatoid arthritis, phlebotomy is not started early, and familial genetic counseling is not considered. In male subjects with positive rheumatoid factor and joint and liver disease, hereditary hemochromatosis should be considered. More liberal use of genetic testing is justified in such cases.
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PMID:Hereditary hemochromatosis masquerading as rheumatoid arthritis. 1168 50

The object was to analyze, in a nationwide survey, the incidence and course of hereditary hemochromatosis in relation to the degree of iron overload and the presence of organ damage. The study included 179 Danish Caucasian patients with clinically overt hemochromatosis diagnosed between 1948 and 1985. A cohort of 158 patients was followed for a median of 8.5 years (range: 0.2-29.5). From 1951 to 1975, the yearly relative incidence rate was constant: 0.58/100,000 persons >20 years of age. From 1981 to 1985, the yearly relative incidence rate rose to 1.40/100,000 persons >20 years of age. Survival was reduced in the entire series when compared with a matched control population ( p<0.0001). There was a steady increase in survival from 1948 to 1985 ( p<0.002). Survival was significantly reduced in patients with liver cirrhosis and/or diabetes mellitus ( p<0.01). In contrast, survival in patients without cirrhosis or diabetes was similar to rates expected. Survival in patients with arthropathy was higher than in patients without joint affection ( p<0.004). Patients adequately treated with phlebotomy ( n=66) had a higher survival than inadequately treated patients ( n=62; p<0.0001). Adequately treated patients with cirrhosis and/or diabetes had better survival than inadequately treated patients with similar organ damage ( p<0.001). The main causes of death were hepatic failure due to cirrhosis (32.0%) and cirrhosis with liver cancer (23.1%). Sharpened diagnostic awareness has improved early diagnosis and increased the diagnostic frequency of clinical hemochromatosis. Adequate phlebotomy treatment was the major determinant of survival and markedly improved prognosis. Early detection and treatment of this common iron overload disorder is crucial and can completely prevent any excess mortality caused by hemochromatosis.
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PMID:Clinically overt hereditary hemochromatosis in Denmark 1948-1985: epidemiology, factors of significance for long-term survival, and causes of death in 179 patients. 1179 15

Hereditary hemochromatosis is the most common inherited single-gene disorder in people of northern European descent. It is characterized by increased intestinal absorption of iron, with deposition of the iron in multiple organs. Previously, the classic description was combined diabetes mellitus, cutaneous hyperpigmentation and cirrhosis. Increasingly, however, hereditary hemochromatosis is being diagnosed at an earlier, less symptomatic stage. The diagnosis is based on a combination of clinical, laboratory and pathologic findings, including elevated serum transferrin saturation. Life expectancy is usually normal if phlebotomy is initiated before the development of cirrhosis or diabetes mellitus. Hereditary hemochromatosis is associated with mutations in the HFE gene. Between 60 and 93 percent of patients with the disorder are homozygous for a mutation designated C282Y. The HFE gene test is useful in confirming the diagnosis of hereditary hemochromatosis, screening adult family members of patients with HFE mutations and resolving ambiguities concerning iron overload.
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PMID:Recognition and management of hereditary hemochromatosis. 1189 57

There is a paucity of data regarding hepatic allograft iron accumulation in patients undergoing orthotopic liver transplantation (OLT) in whom severe iron overload was present in the native explanted liver. Our aim is to evaluate the frequency and cellular distribution of stainable iron in early and late post-OLT hepatic allograft biopsy specimens from patients undergoing their first OLT who had excess iron in their native explanted liver. We compared iron-staining patterns in hepatic allograft biopsy specimens at approximately 1 month (early) and 1 to 2 years (late) post OLT in 41 patients with hepatic iron indices greater than 1.9 in the explanted liver (cases) with a selected group of matched controls without explant hemosiderosis. Our cases included 6 patients with a pre-OLT diagnosis of hereditary hemochromatosis and 35 patients with cirrhosis and secondary iron overload. Early iron deposition was mild in most cases, commonly affected Kupffer's cells, and was seen with similar frequency in cases and controls (41% v 27%; P =.29). Stainable iron was observed in 20 donor livers (12 cases, 8 controls), and all 20 subjects showed stainable iron in 1-month hepatic allograft biopsy specimens. Liver samples from 35 matched pairs were studied for late iron deposition. Iron deposition was observed in 43% of cases versus 17% of controls (P =.06). In conclusion, the frequency of stainable iron in early hepatic allograft biopsy specimens was not different between patients with versus without pre-OLT hepatic hemosiderosis. There was a suggestion that patients with severe pre-OLT hemosiderosis had a greater frequency of iron accumulation in late hepatic biopsy specimens.
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PMID:Liver allograft iron accumulation in patients with and without pretransplantation hepatic hemosiderosis. 1196 76

A 14-year-old girl demonstrated increased iron concentration and transferrin saturation, suggesting iron overload of unknown origin. Liver biopsy showed no fibrosis or hepatocytic atrophia. Nevertheless, Prussian blue reaction for histochemical detection of iron demonstrated very weak positive granules in a few hepatocytes on the periphery of hepatic lobules in close connection to bile capillaries. This very early stage of hemochromatosis was confirmed by TEM and EELS for iron accumulation inside hepatocytic lysosomes and residual bodies. Such siderosomes were scarce in number and iron content, compared to a case of manifested hemochromatosis and liver cirrhosis (Jonas L, Fulda G, Salemeh T, et al. Ultrastruct Pathol. 2001; 25: 111-118.). Liver iron concentration as measured by inductively coupled plasma-mass spectrometry (ICP-MS) and atomic absorption spectrometry (AAS) yielded 2.005 mg/g tissue dry weight, which was considered not significantly increased. In the absence of known causes for secondary iron overload, the early diagnosis was evidenced by genotyping, revealed homozygosity for the HFE gene C282Y mutation, demonstrating the presence of hereditary hemochromatosis.
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PMID:Hereditary hemochromatosis of a young girl: detection of early iron deposition in liver cell lysosomes using transmission electron microscopy and electron energy loss spectroscopy. 1202 55


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