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 duck hepatitis B virus (DHBV) genome cloned from a domestic duck from the People's Republic of China has been sequenced and exhibits no variation in sequences known to be important in viral replication or generation of gene products. Intrahepatic transfection of a dimer of this viral genome into ducklings did not result in viremia or any sign of virus infection, indicating that the genome was defective. Functional analysis of this mutant genome, performed by transfecting the DNA into a chicken hepatoma cell line capable of replicating wild-type virus, indicated that viral RNA is not encapsidated. However, virus core protein is made and can assemble into particles in the absence of encapsidation of viral nucleic acid. Using genetic approaches, it was determined that a change of cysteine to tyrosine in position 711 in the polymerase (P) gene C terminus led to this RNA-packaging defect. By site-directed mutagenesis, it was found that while substitution of Cys-711 with tryptophan also abolished packaging, substitution with methionine did not affect packaging or viral replication. Therefore, Cys-711, which is conserved in all published sequences of DHBV, may not be involved in a disulfide bridge structure essential to viral RNA packaging or replication. Our results, showing that a missense mutation in the region of the DHBV polymerase protein thought to be primarily the RNase H domain results in packaging deficiency, support the previous findings that multiple regions of the complex hepadnaviral polymerase protein may be required for viral RNA packaging.
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PMID:Naturally occurring point mutation in the C terminus of the polymerase gene prevents duck hepatitis B virus RNA packaging. 130 4

Sera from 103 patients were tested for hepatitis C virus RNA by nested polymerase chain reaction assay. Using primers from the highly conserved 5'-untranslated region, we detected hepatitis C virus RNA in 67 (88.2%) of 76 patients positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. Hepatitis C virus RNA was detected in 93% of patients who had been infected for 10 yr or less and in 89% of those who had been infected for longer than 10 yr. Hepatitis C virus RNA was detected in all patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma and in 50% of those with nonspecific reactive hepatitis or inactive cirrhosis. Hepatitis C virus RNA was not detected in sera from 22 patients negative for antibody to hepatitis C virus or in 5 patients positive for antibody to hepatitis C virus by second-generation but not by neutralization enzyme immunoassay. Using primers from the less conserved nonstructural region 4, we detected hepatitis C virus RNA at a lower frequency, in 66% of patients who were positive for antibody to hepatitis C virus by both second-generation and neutralization enzyme immunoassays. The detection rate was higher in patients with frequent parenteral exposure. Our study showed that hepatitis C viremia can be detected in most patients with hepatitis C virus infection, including those with long-standing infection or advanced liver disease.
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PMID:Hepatitis C viremia in patients with hepatitis C virus infection. 131 37

Human papillomaviruses (HPV) have been linked causally to some human cancers such as cervical carcinoma. To determine whether any additional type of human malignancy contained HPV DNA, we examined 16 hepatocellular carcinoma (HCC) specimens by Southern blot technique and by polymerase chain reaction (PCR). One HCC contained HPV 16 DNA as demonstrated by both Southern blot and PCR. Two other HCC samples contained HPV 18-related nucleotide sequences by PCR but were negative by Southern blot of genomic DNA. HPV could have been carried via blood to the liver, thus indirectly supporting the presence of an HPV viremia. Our findings suggest that oncogenic HPV might constitute a cofactor acting synergistically with hepatitis B virus (HBV) in the development of the HCC in these patients. Alternatively, the presence of HPV in the tumor tissue might be the result of an opportunistic infection.
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PMID:Detection of human papillomavirus in primary hepatocellular carcinoma. 132 Mar 56

Wild duck populations were investigated over a 4 year period for duck hepatitis B virus (DHBV) infection and liver disease. It appeared that DHBV is endemic in wild migratory mallards from France and the U.S.A., although neither hepatocellular carcinoma nor viral DNA integration could be detected in liver samples examined. The follow up of natural infection indicated that wild mallards developed significantly higher serum titres to DHBV DNA than Pekin ducks. The results of experimental transmission demonstrated that such differences in viraemia were not related to the breed of ducks but to the virus isolate, since the wild mallard-isolated DHBV (DHBV WM) induced significantly higher viraemia in both mallard and Pekin ducklings compared to the domestic Pekin DHBV (DHBVP) isolate. The naturally infected mallard and Pekin ducks had only minor histological lesions of the liver compared with experimentally infected birds. There was no correlation between the intensity of viraemia and the severity of liver lesions, suggesting that as for mammalian hepadnaviruses the hepatic injury in DHBV-infected ducks is probably immunologically mediated.
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PMID:Natural and experimental infection of wild mallard ducks with duck hepatitis B virus. 199 78

Hepatitis D virus and hepatitis B virus nucleic acids were detected by Northern and Southern blot hybridization in the sera and livers of 85 chronic carriers of HBsAg and anti-hepatitis D followed up for a mean of 10 yr. We identified three subsets of patients: 13 with hepatitis D virus and hepatitis B virus viremia, 53 with serum hepatitis D virus RNA, but without hepatitis B virus DNA and 19 negative for both nucleic acids. Genomic and subgenomic forms of hepatitis D virus RNA were detected only in patients with hepatitis D virus and hepatitis B virus viremia. Histological findings and disease activity at admission were comparable in the three groups of patients, but the outcome was significantly worse in patients with active replication of both viruses; two of them died of terminal liver failure and hepatocellular carcinoma developed in two; the remaining patients had an uneventful course. These results suggest that active hepatitis B virus replication represents an important previously unrecognized determinant of severe liver damage in patients with chronic hepatitis D virus infection. Since hepatitis B virus provides the means for hepatitis D virus secretion and release from infected cells, active hepatitis B virus multiplication favoring the spread of hepatitis D virus from cell to cell may increase the pathogenetic potential of the defective agent.
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PMID:Hepatitis B virus replication modulates pathogenesis of hepatitis D virus in chronic hepatitis D. 199 12

The study of two major risk factors in the development of hepatocellular carcinoma, namely persistent hepatitis virus infection and exposure to dietary aflatoxins, has been hampered by lack of an experimental system. To this end we have used a Pekin duck model to examine the effect of congenital duck hepatitis B virus (DHBV) infection and aflatoxin B1 (AFB1) exposure in the induction and development of liver cancer. AFB1 was administered to DHBV infected or noninfected ducks at two doses (0.08 and 0.02 mg/kg) by i.p. injection once a week from the third month posthatch until they were sacrificed (2.3 years later). Two control groups of ducks not treated with AFB1 (one of which was infected with DHBV) were observed for the same period. Each experimental group included 13-16 ducks. Higher mortality was observed in ducks infected with DHBV and treated with AFB1 compared to noninfected ducks treated with AFB1 and other control ducks. In the groups of noninfected ducks treated with high and low doses of AFB1, liver tumors developed in 3 of 10 and 2 of 10 ducks; in infected ducks treated with the high dose 3 of 6 liver tumors were observed and none in the low dose of AFB1. No liver tumors were observed in the two control groups. Ducks infected with DHBV and treated with AFB1 showed more pronounced periportal inflammatory changes, fibrosis, and focal necrosis compared to other groups. All DHBV carrier ducks showed persistent viremia throughout the observation period. An increase of viral DNA titers in livers and sera of AFB1 treated animals compared to infected controls was frequently observed. No DHBV DNA integration into the host genome was observed, although in one hepatocellular carcinoma from an AFB1 treated duck, an accumulation of viral multimer DNA forms was detected. The metabolism of AFB1 in infected and noninfected duck liver was also examined. The study on the role of DHBV infection and AFB1 in the etiopathogenesis of liver tumors may help to clarify some of the basic mechanisms of carcinogenesis.
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PMID:Contribution of aflatoxin B1 and hepatitis B virus infection in the induction of liver tumors in ducks. 210 70

A 'blind' recombinant immunoscreening approach, of general application to studies of infectious diseases, was used to clone and identify the genome of the previously uncharacterized non-A, non-B hepatitis (NANB) virus. This agent is a positive-stranded RNA virus that appears to be distantly related to the flaviviridae family. A recombinant viral antigen (C100-3) was used to develop a capture assay for circulating antibody. Data obtained using this assay indicate that this agent, termed the hepatitis C virus (HCV), is the major cause of post-transfusion, community-acquired and cryptogenic, NANB. Anti-C100-3 antibody appears to be directed towards dominant, non-structural viral epitopes. It is a non-neutralising antibody that develops generally late in infection and is a particularly good marker of chronic, persistent viraemia. Many asymptomatic but infectious blood donors can now be detected using this antibody assay. HCV is associated with the development of hepatocellular carcinoma and possibly, other liver diseases.
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PMID:Hepatitis C virus: the major causative agent of viral non-A, non-B hepatitis. 211 12

Twenty-nine Pekin ducks were inoculated with duck hepatitis B virus (DHBV), DHBV-free serum, or saline at 1 day of age. Congenitally DHBV-infected ducks were also studied. Ducks were killed periodically during a 92-week study and examined histologically and immunohistochemically to assess liver and extrahepatic inflammation and to detect and characterize DHBV core antigen tissue distribution. DHBV infection produced an asymptomatic but persistent DHBV viremia in all ducks associated with a mild to moderate transient hepatic inflammation apparent at 3 to 6 weeks post-inoculation and waning afterwards. DHBV core antigen was detected in hepatocyte cytoplasm at 1 week post-inoculation, and by 3 weeks post-inoculation scattered pancreatic acinar and islet cells also contained viral antigen. Small numbers of mononuclear cells in the splenic white pulp also contained viral antigen. Viral antigen persisted in all of these tissues throughout the duration of the experiment. No inflammation or tissue injury was detected in any of the extrahepatic tissues during the course of DHBV infection. One DHBV-injected duck developed a hepatocellular carcinoma at 88 weeks of age. Isolated patches of neoplastic hepatocytes contained cytoplasmic DHBV core antigen. The results of this study indicate that DHBV, like mammalian hepadnavirus, is capable of producing a persistent infection of the liver and several extrahepatic tissues and suggest that persistent infection may be associated with the development of hepatocellular carcinoma.
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PMID:A sequential histologic and immunohistochemical study of duck hepatitis B virus infection in Pekin ducks. 254 May 86

To search for events underlying reduction of peripheral viremia and integration of hepatitis B virus (HBV) DNA into the liver cell genome in long-term virus carriers with hepatocellular carcinoma, paired samples of liver and tumor tissue were analyzed by molecular hybridization and immunological methods. Most tumor tissues contained integrated viral DNA; in none was extrachromosomal HBV DNA detected. Integrated HBV DNS was also found in peritumor liver tissue in the majority of patients. However, liver of patients either with or without peripheral viremia also contained free HBV DNA and replicative intermediates. In three nonviremic patients with replicative HBV DNA in liver, viral core antigen expression was markedly reduced or absent, whereas viral envelope protein (surface antigen) expression was normal. In one case, replicative intermediates in liver were sensitive to DNase I digestion, indicating that viral DNA was not encapsidated in normal viral core particles. These results suggest that decreased or defective core antigen production can lead to reduced viremia associated with blocked virus assembly/secretion and accumulation of unencapsidated HBV DNA replicative intermediates in the liver cell. Accumulation of such HBV DNA molecular forms in the liver may lead to an increased propensity for HBV DNA to integrate into the host genome, which has been found with high frequency in hepatic neoplasms from patients infected with hepatitis B virus.
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PMID:Interrupted replication of hepatitis B virus in liver tissue of HBsAg carriers with hepatocellular carcinoma. 284 38

To elucidate the biologic significance of hepatocyte HBsAg, its expression patterns were correlated with virus replication and liver pathology in 578 liver biopsies taken from chronic HBsAg carriers aged 1 to 80 years. Five major patterns of hepatocyte HBsAg were identified: homogeneous [intense and discrete, (Pattern A), faint and discrete, (Pattern B) and faint and grouped (Pattern C)]; globular or spotty (Pattern D), and marginal (Pattern E). Pattern A was always associated with viremia and also very frequently with membrane HBsAg expression, but rarely with active liver disease. It occurred most commonly in HBeAg-positive carrier children and young adults, reflecting an early immune tolerance phase with active virus replication. Pattern B was also usually associated with viremia, but very commonly associated with active disease (70%), reflecting active virus replication with enhanced immune response. Pattern E (marginal HBsAg), which was always in group distribution resembling a clonal expansion, predominated the HBeAg-negative phase and was associated with absence of viremia and occurred mostly in older adults with inactive bipolar disease spectrum (normal liver/mild disease or cirrhosis/hepatocellular carcinoma); this reflects a late phase of inactive virus replication or integration. Patterns C and D did not correlate well with viremia, but also tended to have inactive diseases as did Pattern E. These findings suggest that hepatocyte HBsAg expression is closely related to the natural course of chronic hepatitis B virus infection.
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PMID:Correlation of hepatocyte HBsAg expression with virus replication and liver pathology. 339 3


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