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)

We studied the relationship between hepatocyte proliferation and hepatitis delta virus (HDV) replication at the single cell level. The proliferating cell nuclear antigen (PCNA) (by immunohistochemistry) and the HDV RNA (by in situ hybridization) were stained in neoplastic and non-neoplastic liver tissues of 19 patients with chronic HDV infection, including four cases of cirrhosis with superimposed hepatocellular carcinoma (HCC). As controls, we assessed the hepatocyte proliferation of liver tissues from 16 patients with chronic hepatitis B and on three normal livers. The hepatocyte PCNA labelling index of HDV-infected tissues was comparable with that seen in chronic hepatitis B-infected livers but was significantly higher than that observed in normal livers. Although cirrhotic tissues had lower hepatocyte proliferating fractions than non-cirrhotic tissues, the difference was not statistically significant. The hepatocyte proliferation rate did not correlate with the level of intrahepatic HDV replication or with the histological activity. In double-labelling experiments, PCNA and HDV RNA staining did not co-localize, with the exception of two of three cirrhotic tissues associated with HCC, where the association between the two markers was statistically significant. This co-localization was not observed, however, in the adjacent tumorous tissues. In patients with chronic HDV infection the hepatocyte proliferation was increased with respect to normal liver tissue, but was comparable with that observed in patients with chronic hepatitis B virus infection and did not correlate with the level of HDV replication or the histological activity. In the cirrhotic tissue of patients with HCC (but not in the tumour counterpart), HDV RNA may occasionally co-localize with the marker of hepatocyte proliferation. Whether this association between viral replication and cell division is related to liver carcinogenesis remains to be established.
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PMID:Relationship between hepatocyte proliferation and hepatitis delta virus replication in neoplastic and non-neoplastic liver tissues. 909 64

While the cytological features of hepatocellular carcinoma on fine needle aspiration cytology are well described, cases of hepatocellular carcinoma with malignant cells in ascitic fluid and their characteristics are not. A patient is described with cirrhosis resulting from chronic hepatitis B virus infection, ascites, and hepatocellular carcinoma diagnosed by effusion cytology. The malignant cells in the effusion were shown to be positive for alpha fetoprotein using immunocytochemistry, and for human albumin using in situ hybridisation, confirming the diagnosis of hepatocellular carcinoma. Further investigations in a terminally ill patient were thus avoided.
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PMID:Effusion cytology of hepatocellular carcinoma with in situ hybridisation for human albumin. 921 33

Hepatitis B viruses can cause chronic liver diseases in both children and adults. In hyperendemic areas, although most related complications occur during adulthood, nearly half of the primary infection in chronic hepatitis B virus carriers occurs in perinatal period through maternal transmission and the other half are from horizontal transmission mainly through intrafamilial spread or injection using unsterilized needles. Children with chronic hepatitis B virus infection are mostly asymptomatic. They are generally active and growing well with very rare exceptions. Even with acute exacerbation of liver function and active inflammation, jaundice or growth failure is uncommon. Mild histologic abnormalities in the liver begins early in life and may progress to severe liver impairment in later life. Severe liver damage, with bridging hepatic necrosis or fibrosis, or cirrhosis of the liver may occur, but is rare during childhood. Universal immunization program of hepatitis B virus has been proved to be effective in reducing hepatitis B carrier rate for more than 10 folds, and the incidence of hepatocellular carcinoma in children has also been reduced significantly.
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PMID:Hepatitis B: long-term outcome and benefits from mass vaccination in children. 965 11

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor that is prevalent in Southeast Asia. Although the etiological factors associated are now well recognized, the interactions between individual factors and the molecular mechanisms by which they lead to cancer remain unclear. Cytogenetic analysis on HCC has been limited because of poor hepatocyte growth in vitro. The recently developed technique of comparative genomic hybridization (CGH), however, permits screening of the entire genome without the need of cell culture. CGH was applied to the study of genomic aberrations in 67 surgically resected samples of HCC, 3 of adenomatous hyperplasia (AH), and 12 of nontumorous cirrhotic liver surrounding the tumors. All samples were from patients of a racially and etiologically homogeneous population in Southern China, where chronic hepatitis B virus infection is the main etiological factor. CGH analysis of the HCC samples revealed frequent copy number gain of 1q (48/67 cases, 72%), 8q (32/67 cases, 48%), 17q (20/67 cases, 30%), and 20q (25/67 cases, 37%) and common losses on 4q (29/67 cases, 43%), 8p (25/67 cases, 37%), 13q (25/67 cases, 37%), and 16q (20/67 cases, 30%). Our finding of a high incidence of 1q gain strongly suggested this aberration was associated with the development of HCC. Genomic abnormalities were detected in 1 of the 3 AH specimens but absent in all 12 cirrhotic tissues surrounding the tumor. Clinical staging classified 3/67 HCC cases as T1, 53 cases as T2, and 11 cases as T3. No significant difference in the pattern of genomic imbalances was detected between stages T2 and T3. A significant copy number loss of 4q11-q23 was, however, identified in those tumors larger than 3 cm in diameter. Of particular interest was the identification of 8q copy number gain in all 12 cases of HCC that arose in a noncirrhotic liver, compared with only 20/55 cases in HCC arising in a cirrhotic liver. We suggest that 8q over-representation is likely associated with a growth advantage and proliferative stimulation that have encouraged malignant changes in the noncirrhotic human liver.
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PMID:Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: relationship to disease stage, tumor size, and cirrhosis. 991 16

Infection with hepatitis B virus can lead to serious long-term complications including chronic hepatitis B virus infection leading to hepatocellular carcinoma, liver failure, and death. We report a case of prolonged hepatitis B antigenemia after routine vaccination with Engerix B. A positive hepatitis B surface antigen was found when the individual donated blood 18 days after vaccination. This resulted in rejection of the donated blood and permanent deferral from further donation. It also led to referral to a physician, creating anxiety in the individual and additional unnecessary testing. Additional studies are needed to identify the length to time of hepatitis B surface antigenemia after hepatitis B vaccination, and blood collection centers should be aware of the potential for donors to have a prolonged false-positive hepatitis B surface antigen after vaccination against hepatitis B. hepatitis B, hepatitis B vaccine, hepatitis B surface antigen, vaccine-induced positive hepatitis B surface antigen, Engerix B.
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PMID:Prolonged hepatitis B surface antigenemia after vaccination. 1083 94

Infection by hepatitis B virus remains a major health problem in the world despite the availability of effective vaccines. Although vaccination programs targeting high risk groups have been pushed to their limits, high prevalence rates persist especially in endemic zones. More recently mass vaccination programs conducted on Taiwan have demonstrated the efficacy of this approach with a decrease in the number of chronic hepatitis B virus carriers in the general population in association with a decrease in the incidence of hepatocellular carcinoma, one of the most serious complications of chronic hepatitis B virus infection. Side effects have been reported including the risk of central nervous system demyelination. However studies have shown no evidence of a significant correlation between vaccination and this type of disease. Occurrence of hepatitis B in properly vaccinated subjects could result from selection of mutant viral strains able to escape detection by the immune system. The recently revised benefit-to-risk ratio remains highly favorable for vaccination. Current data indicates that the policy of mass vaccination of the population should be pursued.
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PMID:[Vaccination against hepatitis B virus: current data]. 1090 55

Previously, we have linked prolonged intense mitogen-activated protein kinase (MAP kinase; MAPK) signaling in hepatocytes to increased expression of p21(Cip-1/WAF1/MDA6) (p21) and p16(INK4a) (p16), that leads to a p21-dependent growth arrest. In this study, we investigated the impact of hepatitis B virus X protein (pX) expression on MAPK-modulated cell cycle progression in primary mouse hepatocytes. In hepatocytes, expression of pX enhanced protein levels of p21 and p27, but not of p16. The elevated levels of p21 and p27 correlated with reduced DNA synthesis in wild-type (+/+) hepatocytes and with a weak stimulation of DNA synthesis in p21 null (-/-) cells. Antisense p27 messenger RNA (mRNA) (p27as) increased DNA synthesis in +/+ and p21 -/- cells, and pX blunted this effect in +/+ cells. In p21 -/- cells, however, p27as permitted pX to further stimulate DNA synthesis. These data argue that a reduced ability to enhance expression of both p21 and p27 is required to fully reveal the growth-potentiating properties of pX. This finding also implies that depending on the functional status of the p21 and p27 genes, expression of pX can have 2 very different effects on hepatocyte proliferation. Prolonged intense MAPK signaling reduced DNA synthesis in +/+ cells and enhanced DNA synthesis in p21 -/- cells. The enhancement of DNA synthesis in p21 -/- cells was blocked by pX, and the effect of pX was abrogated by p27as. Furthermore in p21 -/- cells, overexpression of p16 blocked MAPK-stimulated DNA synthesis, and this effect was partially reversed by p27as. These data argue that p27 can also cooperatively interact with p16 to inhibit DNA synthesis in hepatocytes. Collectively, our findings show that reduced expression of p16, p21, and p27, which can occur during hepatocellular carcinoma, enhances the ability of MAPK signaling and pX to cause proliferation in hepatocytes. Thus loss of cyclin kinase inhibitor function may play an important role in the process of tumor progression after chronic hepatitis B virus infection.
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PMID:Hepatitis B virus X protein increases expression of p21(Cip-1/WAF1/MDA6) and p27(Kip-1) in primary mouse hepatocytes, leading to reduced cell cycle progression. 1167 61

Anti-Golgi antibodies are a type of anticytoplasmic autoantibody rarely found during routine examination of pathological samples. Although they have been mostly associated with connective autoimmune diseases, they are also present in other clinical conditions, including few cases of liver dysfunction. In this report, we describe for the first time the presence of high titres of anti-Golgi antibodies in a patient with virus-C-induced hepatocellular carcinoma (HCC). By immunofluorescence, the patient's serum yielded a characteristic fluorescence pattern that corresponded to the presence of Golgi reactivity. On immunoblot, the serum disclosed three reactive bands of approximately 105, 79 and 59 kDa. In addition, we retrospectively analysed the presence of anti-Golgi antibodies in sera from 95 patients with chronic hepatitis C, in 32 patients with chronic hepatitis B, in 35 patients with HCC associated with either virus C (27 cases), virus B (five cases) or both virus C and virus B (three cases), and in 18 patients with HCC induced by alcoholism. We found an additional positive patient, beside the patient presented herein, with HCC induced by B virus infection, whereas all patients without HCC were negative. Thus, the overall frequency of anti-Golgi antibodies in our series of patients with virus-induced HCC was 5.5% (two cases out of 36). The mechanism involved in the appearance of anti-Golgi antibodies in HCC is discussed, along with a review of the reported cases of liver diseases associated with the appearance of Golgi autoantibodies.
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PMID:Autoantibodies to Golgi proteins in hepatocellular carcinoma: case report and literature review. 1216 87

Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and is estimated to cause approximately half a million deaths annually. Because of its high fatality rates, the incidence and mortality rates are almost equal. The major risk factors for HCC are chronic hepatitis B virus infection, chronic hepatitis C virus (HCV) infection, and alcoholic cirrhosis. The epidemiology of HCC is characterized by marked demographic (age, gender, race/ethnicity) and geographic variations. Hepatitis B virus infection, with and without aflatoxin exposure, is responsible for most cases in developing countries; better control of these risk factors has resulted in a recent decline in HCC in some places like Taiwan and China. Recently, however, a trend of rising rates of HCC has been reported from several developed countries in Europe and North America. These new trends are associated with "new" risk factors such as HCV and, possibly, diabetes. In the United States, the incidence of HCC has approximately doubled over the past 3 decades. White individuals are two to three times less often affected than African Americans, who in turn are two to three times less often affected than Asians, Pacific Islanders, or Native Americans. Men are two to three times more often affected than women. Concomitant with the rising rates of HCC, there has been a shift of incidence from typically elderly patients to relatively younger patients between ages of 40 to 60 years. An increase in HCV-related HCC accounts for at least half of the witnessed increase in HCC in the United States. Hepatocellular carcinoma continues to carry an overall dismal survival rate (close to 5%); very few patients qualify for and receive potentially curative therapy. The future incidence trends of HCC will be determined to a large extent by the clinical course of HCV-infected people.
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PMID:Hepatocellular carcinoma: an epidemiologic view. 1239 9

Dietary exposure to aflatoxins is one of the major risk factors for hepatocellular carcinoma. Individual susceptibility to aflatoxin-induced hepatocarcinogenesis may be modulated by both genetic and environmental factors affecting metabolism. A cross-sectional study was performed to evaluate determinants of the formation of aflatoxin covalently bound to albumin (AFB1-albumin adducts). A total of 474 subjects who were free of liver cancer and cirrhosis and were initially selected as controls for previous case-control studies of aflatoxin-induced hepatocarcinogenesis in Taiwan, were employed in this study. Aflatoxin-albumin adducts were determined by competitive enzyme-linked immunosorbent assay, hepatitis B surface antigen and antibodies to hepatitis C virus by enzyme immunoassay, as well as genotypes of glutathione S-transferase M1-1 and T1-1 by polymerase chain reaction. The detection rate of AFB1-albumin adducts was significantly higher in males (42.5%) than in females (21.6%) (multivariate-adjusted odds ratio=2.6, 95% confidence interval=1.4-5.0). The formation of detectable albumin adducts was moderately higher in hepatitis B surface antigen carriers (42.8%) than in non-carriers (36.6%) (multivariate-adjusted odds ratio=1.4, 95% confidence interval=1.0-2.1). In addition, the detection rate of AFB1-albumin adducts tended to increase with the increasing number of null genotypes of glutathione S-transferase M1-1 and glutathione S-transferase T1-1. In conclusion, this cross-sectional study has assessed the relative contributions of environmental exposure and host susceptibility factors in the formation of AFB1-albumin adducts in a well characterised Chinese adult population. This study further emphasises the necessity to reduce aflatoxin exposure in people living in an area endemic for chronic hepatitis B virus infection.
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PMID:Determinants of formation of aflatoxin-albumin adducts: a seven-township study in Taiwan. 1243 85


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