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)

A monoclonal antibody, RL23/36, reacting preferentially with a determinant expressed on normal human hepatocytes is described. Use of an immunohistochemical technique on frozen sections from a range of 75 human liver biopsy specimens revealed that the determinant detected by RL23/36 was not expressed on hepatocytes from a number of patients with biopsy-proven liver disease. Although a normal staining pattern was observed in 28 of 29 biopsy specimens from patients with no evidence of liver disease, the antibody did not bind to hepatocytes in some cases of chronic active hepatitis (2/13), alcoholic liver disease (2/9), haemochromatosis (1/1), cirrhosis (1/2) and liver metastases (2/8). Furthermore, as in a previous study undertaken in the rat, the antibody failed to bind to tumour cells in the single human hepatoma observed in this study. These results suggest that further studies using RL23/36 may shed light on the pathogenesis of a number of liver diseases, including primary hepatocellular carcinoma.
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PMID:A monoclonal antibody reactive with human hepatocytes. 619 94

A review of 180 patients with either chronic hepatitis or hepatocellular carcinoma (HCC) indicate a significant association. 40 patients with chronic hepatitis were seen between 1975-79. 6/25 of chronic active hepatitis and 7/15 with chronic persistent hepatitis were HBsAg positive (RIA). In the 41 patients with HCC, 15 (37%) were alcoholic, 10 cirrhosis (HBsAg positive), 5 haemochromatosis 5 cryptogenic cirrhosis, 2 probably due to sex steroids and in 4 no aetiological factor was apparent. HBsAg was present in 10/22 (45%) of HCC with cirrhosis, 15/256 (6%) for alcoholic cirrhosis, 5/16 (33%) for haemachromatosis and 5/30 (16%) cryptogenic cirrhosis. 8/80 (10%) who had acute viral hepatitis (B) are antigen positive at 6 months. This report shows that Hepatitis B virus infection is now a significant causes of liver injury in 180 patients studied. The majority of patients who have HBsAg positive cirrhosis do not have a history of acute hepatitis.
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PMID:An Australian experience of hepatitis B infection, cirrhosis and hepatocellular carcinoma. 625 12

Despite Scotland's well-recognised alcohol problem, there is scant information of the aetiology of cirrhosis in this country. This study of 222 patients, reviewed 197 cases presenting as cirrhosis and 25 cases presenting as primary liver cell carcinoma (PLCC) in the East Tayside area of Scotland between 1975 and 1979. The survey was based on an analysis of all histologically proven cases of cirrhosis and PLCC encountered during a five-year period. There was a constant rate of presentation of cirrhosis of about 40 new patients per year, with a stable pattern of aetiology. About 55 per cent were due to alcohol, and there was no significant change in this proportion over the study. No evidence was found for an increasing female susceptibility or earlier female morbidity in alcoholic cirrhosis. Cryptogenic cirrhosis, cardiac cirrhosis and secondary biliary cirrhosis were more often diagnosed at post mortem. Ninety one per cent of patients with primary biliary cirrhosis were females, but the expected male preponderance in haemochromatosis was not present. In addition to the 25 patients presenting with PLCC, three of the cirrhotic patients developed the tumour by the end of 1979. Seventy one per cent of PLCC cases arose in already cirrhotic livers, none were HBsAg positive. Bronchopneumonia, hepatic failure, gastrointestinal bleeding and cardiac failure were the most frequent causes of death.
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PMID:Cirrhosis and primary liver cell carcinoma in Tayside: a five year study. 627 84

Two human cases of hepatocellular carcinoma combined with primary hemochromatosis and liver cirrhosis were studied with special reference to liver lesions displaying resistance to iron accumulation, and presence of hepatitis B surface antigen. Hepatocellular carcinomas, as well as small islands of hepatocytes within regenerative nodules, were free of the iron accumulation which otherwise occurred throughout the remainder of the hemochromatotic liver parenchyma. A positive reaction for hepatitis B surface antigen using the orcein staining method occurred randomly in iron-containing hepatocytes and in clusters of iron-containing hepatocytes cirrhotic nodules, but completely iron-free cells of foci and carcinomas were negative for orcein. Therefore, these iron-free foci are suggested to be precursors to the carcinoma.
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PMID:Resistance to iron accumulation and presence of hepatitis B surface antigen in preneoplastic and neoplastic lesions in human hemochromatotic livers. 628 22

Two cases of iron overload in the liver are presented--one of hemochromatosis with associated hepatoma and one of hemosiderosis with probable androgen dependent multicentric hepatic adenomas. Nuclear magnetic resonance scans displayed the tumours as well as low liver parenchymal signal intensity on the saturation-recovery, inversion-recovery, and spin-echo pulse sequences probably as a result of decreased tissue T1 and T2.
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PMID:NMR imaging of the liver in two cases of iron overload. 632 87

Experience over the last 20 years with 34 patients with idiopathic hemochromatosis is summarized and the literature is reviewed. Methods are now available which are highly effective in the diagnosis of iron overload and virtually all diagnoses are made antemortem. The nature of the disease has changed through the removal of iron by phlebotomy. Early deaths are limited to patients with severe and rapidly progressive heart disease and to those presenting with neoplasm. The major mortality has shifted to a much later period and the incidence of hepatoma is increasing. There is particular interest at the present time in family studies since excessive iron stores are frequently found within the family. The significance of intermediate degrees of iron overload is unclear, but future attention should be given to the recognition of iron overload long before clinical manifestations appear.
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PMID:Idiopathic hemochromatosis, an interim report. 698 8

23 descendents of a 74--year-old Englishman who had beta-thalassaemia trait, and died of hepatoma, were studied to discover whether thalassaemia minor alone could predispose to iron overload. Serum ferritin and HLA antigens were assessed in all members, and adults underwent radioiron investigations and liver biopsy. 2 members of the second generation and 1 of the third generation, all of whom had thalassaemia trait, had elevated liver iron concentration, indicating preclinical iron overload. This was not associated with any HLA type. None of the subjects had been treated with exogenous iron. The one member of the second generation who had thalassaemia minor but not iron overload was female, and the 5 members of the third generation with the trait, but with normal serum ferritin levels, were all under the age of 15 years. Members of the family without beta-thalassaemia minor had normal iron metabolism. It is possible that the development of iron overload in 4 members of this family was related to the presence of thalassaemia minor, and not to the inheritance of another abnormal gene causing idiopathic haemochromatosis.
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PMID:Iron overload in beta-thalassaemia minor. A family study. 734 95

In the human metal storage disorders of Wilson's disease and primary haemochromatosis, ion transport and excretion dysfunctions result in the intracellular deposition of copper and iron, respectively. These aberrant accumulations of transition metal ions lead to extensive tissue damage, especially in the liver. In order to investigate the possible role of metal ion-mediated oxygen free radical-generated DNA damage in these processes, DNA was isolated from liver of eight Wilson's disease patients and six haemochromatosis patients. Significant levels of bulky DNA damage were detected in these samples by 32P-postlabelling analysis, but were not found in liver DNA from age-matched controls. This form of novel DNA damage was detected in six out of eight Wilson's patients, varying between approximately 1 and 100 base modifications per 10(8) nucleotides, and in all of the haemochromatosis samples examined; the levels of modified species per 10(8) nucleotides varying from approximately 2 to 50. HPLC analysis of these bulky DNA lesions demonstrated that the species formed in Wilson's disease and in haemochromatosis were chromatographically identical but were not the same as putative purine dimers that can be generated in DNA by in vitro incubation with Cu+/Fe2+ and H2O2 (although the possibility that the adducts detected are closely related has not been ruled out). Analysis of the oxidative base lesion 8-hydroxydeoxyguanosine showed that levels were not elevated in liver DNA from either Wilson's disease or haemochromatosis sufferers. In fact, a statistically significantly lower level of this lesion was found in Wilson's disease patients than in controls. These data suggest that bulky DNA damage present in the liver of both wilson's disease and primary haemochromatosis patients may play a more important role in the induction of tissue damage than 8-hydroxydeoxyguanosine. The novel DNA damage detected by 32P-poslabelling may also be a significant factor in the initiation of neoplasia leading to malignant hepatoma in haemochromatosis patients.
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PMID:Detection of bulky DNA lesions in the liver of patients with Wilson's disease and primary haemochromatosis. 752 89

Hepatocellular carcinoma (HCC) is among the 10 most common tumors in the world. However, incidence is not evenly distributed across the world. In many instances, the proximate cause for the tumor can be identified. Chronic hepatitis B infection is probably the most common cause, followed by chronic hepatitis C. Other important causes are alcoholic liver disease, hemochromatosis, alpha 1-antitrypsin deficiency, and other chronic liver diseases. Although proximate causes may be identifiable, pathogenesis remains uncertain. Factors that may be important include the presence of Aflatoxin B1 in food, genetic changes induced by the hepatitis B virus, and repeated rounds of necrosis and regeneration, also induced by hepatitis viruses. The genes involved and the mutations necessary for hepatic carcinogenesis are unknown, with the sole exception of the p53 gene, which is probably a late phenomenon. Screening for HCC is widely practiced despite the lack of evidence of improved survival. The screening tests used include alphafetoprotein levels and ultrasonography. Screening can identify small tumors; however, survival may not be improved, because the presence of cirrhosis may limit the number of patients who can undergo resections; recurrences or second primary tumors are common; and the presence of chronic liver disease means that survival may be limited anyway. There are many different forms of therapy available; unfortunately, most have not been compared in randomized controlled trials. Surgery remains the therapy of choice if feasible. All other therapy is palliative, including chemotherapy, chemoembolization, hepatic artery embolization, various forms of radiotherapy, and various forms of ablative therapy.
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PMID:Hepatocellular carcinoma. 753 16

The putative relationship between genetic haemochromatosis and PiZ alpha 1 antitrypsin deficiency was studied using a monoclonal antibody against the PiZ variant in 67 consecutive patients with genetic haemochromatosis seen at Karolinska Hospital and Huddinge University Hospital, Stockholm over a 10 year period. Three (4.5%) of the patients with haemochromatosis were found to be PiZ homozygotes (odds ratio = 82, confidence interval = 26, 256; p < 0.0001). The prevalence of the heterozygous (PiZ) phenotype was similar to that in the general population (p = 0.937). During the ascertainment period, liver biopsy was performed in 65 (97%) of the patients; 66% (2 of 3) of the PiZ homozygotes were found to have cirrhosis compared with 10% (6/59) of the non-carriers of the PiZ variant (p = 0.039). None of the homozygous or heterozygous alpha 1 antitrypsin deficient patients had developed hepatocellular carcinoma compared with 3.4% (2 of 59) of the non-PiZ gene carriers (p = 1.0). Two of those with the homozygous phenotype had developed severe emphysema. HLA typing was performed in 18 patients, 16 (89%) of whom manifested antigens known to be linked to haemochromatosis. There were no significant differences between the PiZ gene carriers and non-carriers in mean age at onset of disease, sex distribution, or HLA type. Two of the PiZ heterozygotes had plasma alpha 1 antitrypsin concentrations below the normal range, though the group mean was lower than that of the non-PiZ carriers (p = 0.0003). The data suggest that the presence of the PiZ allele for alpha1 antitrypsin deficiency, in a double dose, is associated with genetic haemochromatosis and may contribute to the earlier onset of cirrhosis in these patients, though it does not increase the risk of hepatocellular carcinoma.
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PMID:Increased PiZ gene frequency for alpha 1 antitrypsin in patients with genetic haemochromatosis. 761 85


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