Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The triad of hemochromatosis, hepatoma and erythrocytosis is a rare combination. Hemochromatosis is often not recognized until the patient presents with the symptoms of hepatocellular carcinoma and erythrocytosis, and the development of erythrocytosis is an important clue to the under-lying hepatoma. The high serum iron concentration and the high saturation of the iron-binding protein, as well as the typical bone marrow hemosiderin pattern, are important aids in the recognition of hemochromatosis. To date, all patients with this triad have been elderly males. The clinical course is usually one of rapid deterioration and death. The seven previously reported cases have been reviewed and the relationship of the erythrocytosis to the increased production of erythropoietin is discussed.
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PMID:The triad of hemochromatosis, hepatoma and erythrocytosis. 21 27

This article reviews the disease process hemochromatosis, which is now recognized as one of the most common genetic disorders. Hemochromatosis is transmitted as autosomal recessive, and occurs in 3% of persons of Anglo-Saxon descent. It is caused by an inappropriate increase in intestinal iron absorption resulting in deposition of excess iron in tissues. Hemochromatosis usually presents in males in their 40s, and females much later. The most frequent initial symptoms are weakness, lassitude, weight loss, and symptoms related to the onset of diabetes mellitus. The classical triad of cirrhosis, diabetes mellitus, and skin pigmentation occurs late in the disease. There is debate over the value of mass screening for the disorder; however, it is recommended that once a case has been identified family members at risk should be screened. Therapy is directed at removing excess iron by phlebotomy. By instituting early therapy, many of the long-term complications, including cirrhosis and hepatoma, can be prevented. It is imperative that physicians learn to recognize early signs and symptoms of hemochromatosis so that treated patients can expect a normal life span with minimal medical intervention.
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PMID:Recognizing genetic hemochromatosis. 784 64

Hereditary Hemochromatosis (HFE) is one of the most common inherited disorders with an estimated frequency of homozygous patients of 0.002-0.0045. The disease is characterized by increased intestinal iron absorption and progressive iron overload. Affected subjects show clinical symptoms of parenchymal organ damage after the third-fourth decade of life and have a 200 fold increased risk of developing hepatocellular carcinoma. Early diagnosis and treatment prevent complications and may normalize life expectancy of patients. The biochemical and genetic defects leading to progressive iron accumulation are still unknown, but the HFE gene is tightly linked to HLA complex on the short arm of chromosome 6. Utilizing HLA serotypes and the study of several polymorphic markers of 6p21, a linkage analysis of the disease locus was performed in a series of Italian hemochromatosis families. The data obtained by linkage analysis and the study of a family with a double recombinant allowed us to better define the HFE gene location with respect to HLA-class I A and F loci.
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PMID:Linkage analysis of 6p21 polymorphic markers and the hereditary hemochromatosis: localization of the gene centromeric to HLA-F. 851 96

Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related liver damage is linked to an increased risk of hepatocellular carcinoma, but the mechanisms underlying hepatitis C viral activity are not known. We therefore compared hepatocellular proliferative activity in chronic C virus-related hepatitis and in liver damage of other etiology. Hepatocyte proliferation rate was investigated in 56 patients with chronic hepatitis using the Ki67 MIB1 monoclonal antibody in archival material. According to etiology, the patients were subgrouped as follows: HCV (34), HBV (11), Alcohol (4), HCV + Alcohol (4), and Hemochromatosis (3). Proliferation rate was correlated with age, sex, etiology, disease activity, liver iron storage, free-radical production, and glutathione levels by regression and discriminant analysis. HCV-positive patients had significantly more MIB1-positive hepatocytes in the periportal area (P < .011) and in the low-proliferating perivenular area (zones 2 and 3) (P < .05). The number of MIB1-positive cells correlated directly with alanine transaminase (ALT) levels, Knodell index (KI), and, inversely, with iron saturation. By stepwise discriminant analysis, ALT levels and etiology were identified as single independent variables. These data suggest that HCV infection induces increased and abnormal hepatocyte proliferation, which might be related to the increased risk of hepatocellular carcinoma in patients with HCV-related liver damage.
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PMID:Hepatocyte proliferative activity in chronic liver damage as assessed by the monoclonal antibody MIB1 Ki67 in archival material: the role of etiology, disease activity, iron, and lipid peroxidation. 867 66

We described a clinicopathological study of primary hepatoma associated with alcoholic liver diseases without viral liver diseases. In 150 patients with primary hepatoma, 6 patients (4%) have hepatoma associated with pure alcoholic liver disease, although 143 hepatoma were associated with chronic viral liver diseases and one was with primary biliary cirrhosis. All patients were male. The diagnosis of hepatoma was obtained at the age of 54 to 67 years old, and the duration of ethanol intake was 33 to 40 years. Three cases had a history of temperance. As an underlying liver disease, liver fibrosis was found in 3 cases and liver cirrhosis was in 3 cases. Chronic infections of hepatitis B and C viruses were ruled out by assaying serum virus markers. Autoimmune hepatitis and primary biliary cirrhosis were neglected by serum autoantibody. Hemochromatosis and Wilson's disease were also excluded. Hepatocellular carcinoma was diagnosed histologically in all the cases. Serum alpha-fetoprotein and PIVKA-II were positive in patients with advanced hepatocellular carcinoma. In cases with small hepatoma, the tumor was resected surgically in two cases and percutaneous ethanol injection against hepatoma was performed in one case. In these cases with small hepatoma, the patients were alive without tumor recurrence during observation period. In advanced hepatoma, transcatheter arterial infusion of anticancer agent was performed in two cases and no therapy was performed due to poor general condition in one case. One case was alive with recurrent hepatoma for 27 months, during which a therapy was repeated five times. Other 2 cases were died. The clinicopathological features of hepatoma associated with alcoholic liver disease were essentially same as those associated with chronic viral infection, although the incidence of hepatoma in alcoholic liver disease was lower than in viral liver disease. The mechanism of hepatocarcinogenesis in alcoholic liver disease was unclear and, therefore, further study of molecular biology and biochemistry was necessary.
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PMID:[A clinicopathological study of primary liver cancer associated with alcoholic liver injury]. 869 40

Hemochromatosis is the most common single gene disorder in Caucasian populations. Regulation of iron balance by intestine is impaired, leading to a widespread deposition of iron, and the disease is associated with an increased risk of hepatocellular carcinoma. Typically the excess of iron treated by phlebotomies is performed in our Blood Center. In 1996 an original paper identifying HFE as a strong candidate gene for hemochromatosis was published and two mutations were described (C282Y and H63D). The former results in a cysteine to tyrosine substitution at amino acid 282 and was found in different patient populations up to 80-90% of patients homozygous for the C282Y mutation. The frequency of the second variant H63D is also increased in hemochromatosis patients but its penetrance is probably not complete. Assessing clinical implications is a new way of identifying patients at risk for this frequent and probably underdiagnosed disease, and important because treatment by venesections is safe with a proven benefit in preventing development of the disease. Four hundred and eighty patients were included in our study and we have shown in this work a correlation between the genotype and the phenotypic presentation of the disorder, with patients homozygous for the C282Y mutation having a greater excess of iron.
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PMID:[The hemochromatosis gene (HFE). Molecular analysis--diagnostic applications]. 978 68

Hereditary hemochromatosis is the most commonly inherited autosomal recessive disorder. Hemochromatosis is a current or potential progression of abnormally high accumulations of iron in the liver. If left untreated, the condition can lead to chronic or irreversible hepatic fibrosis, cirrhosis, hepatocellular carcinoma, arthritis, and organ failure. Common signs and symptoms seen in the primary care setting include fatigue, weakness, abdominal pain, palpitations, skin pigmentation changes, and arthropathy, but any symptom associated with organ damage may be reported. Because prompt intervention can cease or reverse the debilitating effects of iron overload, prompt disease diagnosis and treatments are imperative.
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PMID:Detecting hereditary hemochromatosis. 1091 30

Hemochromatosis was diagnosed in a 14-year-old, male, red ruffed lemur (Varecia variegata ruber) on the basis of abnormal results of serum biochemical analysis, including high serum ferritin and transferrin saturation values, and of liver biopsy. Therapy included chelation, using desferoxamine to remove excess iron and S-adenosylmethionine to improve liver function, and monthly peripheral blood removal by phlebotomy to reduce total body iron content. Response to treatment was assessed by changes in the lemur's attitude and appetite, as well as variations in serum biochemical and iron panel values. Initial improvement was associated with the onset of therapy. After 56 days of treatment, results of serum biochemical analysis indicated a decrease in iron panel values. Treatment was temporarily discontinued from days 56 to 65, and the lemur's condition worsened, so therapy was re-instituted. However, the lemur died of hepatocellular carcinoma on day 110 of treatment.
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PMID:Use of desferoxamine and S-adenosylmethionine to treat hemochromatosis in a red ruffed lemur (Varecia variegata ruber). 1502 25

We report the pattern of liver disease revealed by a study of liver biopsies of 277 adults aged 16-85 years old from January 1983 - December 1993. The most common histological diagnoses were: cirrhosis in 22.3%, chronic active hepatitis (CAH) 16.6%, hepatocellular carcinoma (HCC) in 7.2%, fatty changes in 12% of patients. Less common diagnoses included: Cholestasis in 8 (2.8%), Hemochromatosis in 7 (2.5%), periportal fibrosis in 4 (1.4%), Wilson's disease in 3 (1%), Alcoholic hepatitis in one patient and lymphoma in one patient. Inadequate specimens were encountered in 7 (2.5%). The commonest causes of liver cirrhosis were: Hepatitis C virus (HCV) in 73.3% of patients tested for it and hepatitis B virus (HBV) in 23.2%. Complications related to the procedures were exceedingly low. One patient, with Budd-Chiari Syndrome required emergency laparotomy to control bleeding. In conclusion, liver cirrhosis, CAH and HCC were common patterns of chronic liver disease in this series. HCV was the most common cause of CAH and liver cirrhosis.
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PMID:Pattern of liver disease in a Saudi patient population: a decade of experience at security forces hospital, Riyadh, KSA. 1986 42

Hemochromatosis has generally been considered to be a genetic disease in which progressive iron accumulation over many years can lead to cirrhosis of the liver, hepatocellular carcinoma, diabetes, cardiomyopathy, and arthropathy. Iron depletion by phlebotomy has been the recommended therapy although a randomized trial of phlebotomy versus no treatment has never been reported. Since the discovery of the HFE gene in 1996, it has been possible to predict the risk of developing iron overload by a simple blood test to detect C282Y homozygotes of the HFE gene. The application of the hemochromatosis genetic test in large population studies often initiated to investigate other diseases has provided a fascinating glimpse into the natural history of untreated C282Y homozygotes followed for over 20 years without phlebotomy treatment. These observations are summarized in this review article which raises questions about the need for phlebotomy in all C282Y homozygous patients.
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PMID:The natural history of untreated HFE-related hemochromatosis. 1990 50


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