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)

In this paper, we describe a clinicopathological study of primary hepatocellular carcinoma (HCC) associated with alcoholic liver disease without hepatitis virus infection. In 180 HCC patients who were admitted to Asahikawa Medical College Hospital from 1987 to 1995, 10 patients (6%) had HCC associated with pure alcoholic liver disease (Al-HCC), whereas the HCC in 165 patients was associated with chronic viral liver diseases, in 2 with primary biliary cirrhosis, in 1 each with coexistence of the hepatitis C virus infection and hemochromatosis, and in 2 with cirrhosis of unknown origin. In the Al-HCC group, all patients were male. The diagnosis of HCC was obtained at the age of 54 to 67 years old, and the duration of ethanol intake was 33 to 40 years. Four cases had a history of temperance. As an underlying liver disease, liver fibrosis was found in three cases and liver cirrhosis in seven cases. HCC was diagnosed histologically in all cases. Serum alpha-fetoprotein and PIVKA-II were positive in patients with advanced HCC. In cases with small HCC, the tumor was resected surgically in three cases and percutaneous ethanol injection was performed in two cases. In four cases with small HCC, the patients were alive without tumor recurrence during the observation period. In advanced HCC, transcatheter arterial chemolipiodolization was performed. In the analysis of genetic polymorphism of ALDH 2, all Al-HCC had ALDH 2(1)/2(1).
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PMID:Hepatocellular carcinoma associated with alcoholic liver disease: a clinicopathological study and genetic polymorphism of aldehyde dehydrogenase 2. 898 42

Iron overload has been shown to impair the immune response of the liver, and induce hepatic fibrosis and cirrhosis. Opinions differ concerning the relative risk of developing hepatocellular carcinoma (HCC) in siderotic patients as compared with patients with hepatic fibrosis and cirrhosis and the possible mechanism of liver carcinogenesis in genetic hemochromatosis is still unknown. The purpose of this study is to assess hepatic iron overload, fibrosis and cirrhosis in liver tissue adjacent to hepatocellular carcinoma and in liver tissue of controls in population at risk for hepatocellular carcinoma. Liver tissue was available for examination in 147 biopsies with HCC collected in South Africa. As controls we used liver samples from 211 age and sex matched Africans who died in accidents. Tissue samples were processed routinely, stained with H and E, Sweet's reticulin, Masson's trichrome for fibrous tissue, Prussian blue for iron stain and immunohistochemically for HBsAg. Iron content was assessed with the method described by Brissot. Iron overload was detected in 42.1% of cancerous livers and in 43.7% of livers from controls. The presence of siderosis and iron content gradually increased with the age of studied similarly in cases and in controls. Cirrhosis was present in 32% of cancerous livers and was associated with iron overload in 13%. No cirrhosis and 6% of mild periportal fibrosis not related with siderosis was observed in controls. HBsAg was stainable in 80% of cancerous livers of patients below 25 years of age and in 40% of patients over 35 years. HBsAg in controls was positive in 9%. No relationship of HBsAg and amount of stainable iron in cancerous and livers of controls was found. In conclusion, African siderosis can not play important role in the etiopathogenesis of HCC.
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PMID:Hepatic siderosis, fibrosis and cirrhosis: the association with hepatocellular carcinoma in high-risk population. 942

Although HLA-linked hemochromatosis greatly increases the risk for hepatocellular carcinoma in people of European ancestry, iron overload in Africa is not thought to be etiologically related to this malignancy. To determine if African iron overload may be associated with hepatocellular carcinoma, we reviewed 320 consecutive diagnostic liver biopsies processed at the University of Zimbabwe from 1992 to 1994 and we selected for analysis 215 biopsies from adults that were suitable for the histological assessment of hepatocellular iron. Subjects were stratified according to hepatocellular iron grades of 0-2+ (normal levels to mild siderosis; n = 183) and grades of 3+ and 4+ (distinctly elevated levels consistent with iron overload; n = 32). Thirty-six subjects had hepatocellular carcinoma. Logistic regression modeling revealed a significant association between iron overload and hepatocellular carcinoma after adjustment for age, sex and and the presence of portal fibrosis or cirrhosis (p = 0.041). The odds of hepatocellular carcinoma in subjects with iron overload was 3.1 (95% confidence interval of 1.05-9.4) times that of subjects without iron overload. While we could not test for exposure to viral hepatitis or to aflatoxins in this study, our findings suggest that iron overload may be a risk factor for hepatocellular carcinoma in Africa.
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PMID:African iron overload and hepatocellular carcinoma (HA-7-0-080). 945 25

Chronic hepatitis C and B are the main causes of hepatocellular carcinoma (HCC) worldwide. Little is known about the etiology of HCC in Germany which is regarded as a low-prevalence area for viral hepatitis C (HCV) and B (HBV). To assess the etiologic factors of HCC in Germany we have retrospectively analyzed the records of 100 consecutive patients with hepatocellular carcinoma in our clinic. HCC-patients with documented status on HCV/HBV-infection and daily alcohol intake (n = 55) had HCV antibodies in 53%, HBs-Ag in 20%, isolated chronic alcohol abuse in 11% and genetic hemochromatosis in 2%. In 13% of the HCC-patients no risk factor could be identified. Coinfections with HCV and HBV were not observed. Liver cirrhosis was present in 90% of the HCC-patients. In histologically confirmed HCC (n = 71) serum alpha-fetoprotein level was normal (< 8.5 ng/ml) in 20%, moderately elevated (8.5-300 ng/ml) in 48% and considerably elevated (> 300 ng/ml) in 32% of the patients. Only 31% of all patients presented with small single lesions (< or = 5 cm) without evidence for extrahepatic metastases or portal vein thrombosis. Only 30% of the HCC-patients could be treated with a curative intention (28 hepatic resections, one orthotopic liver transplantation). Patients who underwent resection had cumulative 6-month, 1-year, 2-year and 3-year survival rates of 83.8%, 65.9%, 54.3% and 24.8% respectively. Median survival time after resection was 24.8 months compared with 5.8 months in symptomatically treated patients with unresectable HCC (n = 39). Patients with hepatitis C-associated HCC were significantly older than patients with hepatitis B-associated HCC (mean values: 63.2 vs. 54.2 years). Frequency of cirrhosis, tumor stage, alpha-fetoprotein level and prognosis did not differ between groups. In conclusion hepatocellular carcinoma was predominantly associated with chronic HCV-infection. Most patients presented with normal or moderately elevated serum AFP-levels. Prognosis was poor even after hepatic resection.
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PMID:[Hepatocellular carcinoma in Germany. Epidemiology, etiology, clinical aspects and prognosis in 100 consecutive patients of a university clinic]. 948 38

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

To evaluate the pattern of plasma cyclic adenosine 3',5'-monophosphate, cyclic guanosine 3',5'-monophosphate, atrial natriuretic factor and glucagon levels in different stages of chronic liver diseases, we measured these variables in 20 normal subjects, 25 patients with genetic hemochromatosis, associated with liver cirrhosis in 19 cases and not in six, eight patients with compensated and 15 with decompensated alcoholic or posthepatitic cirrhosis, and 12 with hepatocellular carcinoma. All variables were within the normal range in non-cirrhotic hemochromatotic patients. Cyclic adenosine 3',5'-monophosphate levels were within the normal range (9.5-15.7 nmol/l) in hemochromatotic cirrhotics and elevated in other patients. Cyclic guanosine 3',5'-monophosphate, atrial natriuretic factor and glucagon were above the normal ranges (1.92-5.91 nmol/l, 8.8-62.7 ng/l, and 39-165 ng/l, respectively) in most patients with cirrhosis both with and without hemochromatosis and in most individuals with hepatocellular carcinoma. Cyclic guanosine 3',5'-monophosphate correlated with atrial natriuretic factor in the former groups but not in the latter. These findings indicate that glucagon and atrial natriuretic factor hypersecretion is an early event in cirrhosis, regardless of its etiology. In hepatocellular carcinoma, the underlying cirrhosis may account for most hormonal and metabolic changes although cyclic guanosine 3',5'-monophosphate increases could also be due to the neoplastic process per se.
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PMID:Pattern of plasma cyclic nucleotides and related hormones in liver cirrhosis and hepatocellular carcinoma. 980 95

Cirrhosis of the liver can be regarded as premalignant state, since more than 80 percent of hepatocellular carcinoma (HCC) in the western world develop in a cirrhotic liver. The risk to develop this malignancy depends on the activity of the underlying cirrhosis, its etiology and the duration of the disease. Patients suffering from cirrhosis of the liver due to HBV-, HCV- or HDV-infection and patients with genetic hemochromatosis exhibit a high risk for HCC. This risk is further increased by cocarcinogens, such as alcohol, nicotine and toxins. Ultrasound and AFP-studies aim to diagnose HCC early. The sensitivity of AFP in the serum is remarkably low (about 64%). In contrast a normal AFP-concentration (< 20 ng/ml) carries a high negative prognostic value (> 90%). Patients suspected to suffer from HCC according to the results of screening procedures should be subjected to additional radiologic investigations, such as CT-arterioportography or lipiodol-angiography.
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PMID:[Cirrhosis of the liver as a precancerous condition]. 984 85

The risk of developing hepatocellular carcinoma is significantly increased in patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C infection. The precise mechanisms underlying the development of hepatocellular carcinoma in these conditions are not well understood. Stem cells within the liver, termed oval cells, are involved in the pathogenesis of hepatocellular carcinoma in animal models and may be important in the development of hepatocellular carcinoma in human chronic liver diseases. The aims of this study were to determine whether oval cells could be detected in the liver of patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C, and whether there is a relationship between the severity of the liver disease and the number of oval cells. Oval cells were detected using histology and immunohistochemistry in liver biopsies from patients with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C. Oval cells were not observed in normal liver controls. Oval cell numbers increased significantly with the progression of disease severity from mild to severe in each of the diseases studied. We conclude that oval cells are frequently found in subjects with genetic hemochromatosis, alcoholic liver disease, or chronic hepatitis C. There is an association between severity of liver disease and increase in the number of oval cells consistent with the hypothesis that oval cell proliferation is associated with increased risk for development of hepatocellular carcinoma in chronic liver disease.
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PMID:Oval cell numbers in human chronic liver diseases are directly related to disease severity. 1002 11

Genetic hemochromatosis is an autosomal recessive disorder characterized by excessive iron absorption from the gut, resulting in increased total body iron stores, multisystem organ dysfunction, and an increased risk of hepatocellular carcinoma. The magnetic susceptibility effects of excess hepatocellular iron generally cause diffuse hepatic signal loss on T2- or T2*-weighted MR images. Although hepatic iron deposition is usually diffuse, focal areas of iron sparing can occur, and, when present, superimposed neoplasm is a consideration. We describe a patient with cirrhosis, hemochromatosis, and multiple small benign relatively hyperintense iron-poor foci consisting of piecemeal sideronecrosis.
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PMID:Ferumoxide-enhanced MRI of sideronecrosis superimposed on genetic hemochromatosis. 1005 Aug 15

The synergistic effects of iron overload and ethanol on the liver of mice were studied over a period of 46 weeks. The determination of several parameters (iron, calcium, magnesium, alpha-hydroxyproline, lipid peroxidation, hepatomegalic and splenomegalic indexes) showed that ferrous and ferric lactates provoke an increase of calcium in the liver, higher than that of ethanol in the control animals. The relationship between liver calcium homeostasis modification and the increase of collagen and lipid peroxidation is discussed. Histological examinations showed differences in the tissular characteristics especially when iron and ethanol were given together. These findings suggest the liver calcium homeostasis changes found as a synergistic effect in the early stages of chronic iron overload may be of importance as a trigger of events leading to the pathway of fibrosis-->cirrhosis-->hepatocarcinoma reported in pathologies such as nutritional siderosis and hemochromatosis.
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PMID:Iron-ethanol synergism and pathological liver transformation. 1021 26


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