Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A questionnaire-based survey involving 11,801 hemophiliacs from 54 hemophilia centers in the USA and Europe documented the occurrence of hepatocellular carcinoma (HCC) in 10 patients. The crude rate of HCC was 3.2/100,000 patients/year, at least 30 times higher than the background incidence of this tumor in the countries of origin of the patients. All patients were Caucasians with hemophilia A, 39 to 74 years of age, and had liver cirrhosis. All had one or more risk factor for cirrhosis and HCC: 5 were positive for serum hepatitis B surface antigen, 4 had the antibody to hepatitis C virus, and 4 had histories of alcohol abuse. Serum alpha-fetoprotein, measured in 6 patients, was significantly elevated in 4 (range: 807-1399 ng/ml), and only moderately elevated in 2 (25 and 171 ng/ml). The onset of HCC was asymptomatic in 5 patients, whereas it was accompanied by jaundice, abdominal pain, or ascites in the remaining patients. Thus, HCC seems to be a more important secondary disease for hemophiliacs than formerly recognized. Since HCC is often asymptomatic, screening hemophiliacs with chronic liver disease with periodic ultrasound scans might increase the changes of detecting HCC at a stage amenable to surgical treatment.
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PMID:Hepatocellular carcinoma in hemophilia. 165 Jan 34

The records of one hundred and four patients with confirmed hepatocellular carcinoma seen over a two year period at the National University Hospital were analysed to elucidate the clinical features of our local patients and to assess their response to various therapeutic modalities. Chinese males were over-represented with a peak frequency in the sixth to eighth decade of life. Seventy-five percent of the patients were HBsAg positive and at least 88% had evidence of previous Hepatitis B infection. Ninety-one percent were symptomatic at presentation with pain being the most common symptom. Hepatomegaly with features of cirrhosis were the main physical findings. Seventy percent of the patients presented within three months after the onset of symptoms. The majority of patients had stage II or III disease at diagnosis. Twenty percent of patients had normal alpha-fetoprotein levels. Chemotherapy did not appear to show a survival benefit. Curative surgical resection was feasible in about 10% of patients and it remains the only chance for long term survival. There is an urgent need to identify more effective drugs or other modalities to treat this common and rapidly fatal malignancy. Identification of high risk patients should prompt screening with both serum alpha-fetoprotein and ultrasonography of the liver.
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PMID:Hepatocellular carcinoma--a case series of 104 patients. 165 20

The prevalence of antibody to hepatitis C virus (anti-HCV) was investigated in patients with hepatocellular carcinoma (HCC), and correlated with the clinical features. Anti-HCV was detected in 129 histology or aspiration cytology proven HCC patients and 54 healthy controls. Anti-HCV was examined by the HCV EIA (Abbott Laboratories). All healthy controls were anti-HCV-negative. Nineteen of 81 (23.5%) hepatitis B surface antigen (HBsAg)-positive HCC patients were positive for anti-HCV. Anti-HCV was found among 60.4% (29/48) of HCC patients without detectable HB-sAg. Forty-eight of 129 (37.2%) HCC patients were positive for anti-HCV. There was a significant difference in the prevalence of anti-HCV between patients with HBsAg (23.5%) and those without HBsAg (60.4%, P = 0.0001). However, irrespective of the status of HBsAg, there was no statistical difference in sex, age, routine liver function tests, alpha-fetoprotein concentration, or associated cirrhosis between patients with anti-HCV and those without. The results imply that hepatitis C virus may play a role in the pathogenesis of HCC.
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PMID:Hepatitis C virus antibody in hepatocellular carcinoma in Taiwan. 165 8

One hundred thirty-five hepatocellular carcinomas were examined for the presence of antigenic tumor markers by the avidin-biotin-peroxidase complex method. Ninety-seven were from the US and 38 came from Argentina. The following markers were tested: alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg), hepatitis D delta antigen (HD delta Ag), and Mallory's bodies (MB). In the US cases, AFP was present in 43%, AAT in 41%, HBsAg in 17%, and MB in 48%. Both HBcAg and HD delta Ag were absent. In the cases from Argentina, AFP was found in 26% and AAT in 18%. None of the other antigens were seen. Thirteen US tumors expressed three antigens and two four antigens simultaneously. This study reveals in humans a heterogenous expression of antigens by neoplastic hepatocytes with geographic differences, possibly due to multiple factors such as alcohol consumption or prevalence of hepatitis B infection.
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PMID:Antigenic markers of hepatocellular carcinoma. 168

Hep G2, a human hepatocellular carcinoma, was grown s.c. in nude mice, as well as in tissue culture. This line retains the normal liver parenchymal cell capacity to synthesize human plasma proteins such as albumin, but there is no indication that it harbors the hepatitis B virus. We have detected the oncofetal antigens alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in both Hep G2 xenografts and spent tissue culture media by Ouchterlony double diffusion assays, enzyme-linked immunosorbent assay, and immunohistology. By enzyme-linked immunosorbent assay, the AFP levels were 544.9 ng/ml in the cell culture and 1.6 microgram/g in saline extracts of the xenograft. The CEA levels were 35.2 ng/ml in the cell culture and 5.4 micrograms/g in the xenograft. The biodistribution of a radioiodinated anti-AFP murine monoclonal antibody and an anti-CEA monoclonal antibody were studied separately in nude mice bearing s.c. Hep G2 xenografts in comparison to an isotype-matched irrelevant IgG (Ag8). Anti-CEA antibody showed a preferential localization for Hep G2, but anti-AFP antibody did not. Immunohistochemical studies of the Hep G2 tumor, using biotinylated anti-AFP and anti-CEA, indicate both cytoplasmic and luminal staining of CEA and AFP in the tumor. These results suggest that Hep G2 may be a useful cell line for radioimmunodetection and radioimmunotherapy studies using anti-CEA and possibly anti-AFP monoclonal antibodies.
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PMID:Carcinoembryonic antigen and alpha-fetoprotein expression and monoclonal antibody targeting in a human hepatoma/nude mouse model. 168 35

We studied the effects of transfection of the normal c-Ha-ras gene, rasGly-12, and its oncogenic mutant, rasVal-12, on expression of the alpha-fetoprotein (AFP) and albumin genes in a human hepatoma cell line, HuH-7. The mutant and, to a lesser extent, the normal ras gene caused reduction of the AFP mRNA but not the albumin mRNA level in transfected HuH-7 cells. Cotransfection experiments with a rasVal-12 expression plasmid and a chloramphenicol acetyltransferase reporter gene fused to AFP regulatory sequences showed that rasVal-12 suppressed the activity of enhancer and promoter regions containing A + T-rich sequences (AT motif). In contrast, rasVal-12 did not affect the promoter activity of the albumin and human hepatitis B virus pre-S1 genes even though these promoters contain homologous A + T-rich elements. ras transfection appeared to induce phosphorylation of nuclear proteins that interact with the AFP AT motif, since gel mobility analysis revealed the formation of slow-moving complexes which was reversed by phosphatase treatment. However, similar changes in complex formation were observed with the albumin and hepatitis B surface antigen pre-S1 promoters. Therefore, this effect alone cannot explain the specific down regulation of the AFP promoter and enhancer activity. ras-mediated suppression of the AFP gene may reflect the process of developmental gene regulation in which AFP gene transcription is controlled by a G-protein-linked signal transduction cascade triggered by external growth stimuli.
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PMID:c-Ha-ras down regulates the alpha-fetoprotein gene but not the albumin gene in human hepatoma cells. 169 Aug 41

Woodchuck hepatitis virus infection of the eastern woodchuck represents a useful model for the study of hepatitis B virus infection and disease in humans, including hepatocellular carcinoma. In man, hepatocellular carcinoma is frequently detected and monitored using assays for serum alpha-fetoprotein. To study the relationship between alpha-fetoprotein and woodchuck hepatitis virus-induced hepatocellular carcinoma in the woodchuck model, we produced a monoclonal antibody to woodchuck alpha-fetoprotein and used biophysical and immunochemical methods to demonstrate its specificity and affinity (7 x 10(8) L/mol) for woodchuck alpha-fetoprotein. A competition radioimmunoassay was then developed and standardized for measuring serum alpha-fetoprotein concentrations. In the radioimmunoassay system, woodchuck alpha-fetoprotein was detected between 20 ng/ml (20% to 25% inhibition) and 8,500 ng/ml (97% to 98% inhibition). Elevated serum alpha-fetoprotein concentrations (450 to 452,000 ng/ml) were measured in 21 of 23 woodchucks in the advanced stages of woodchuck hepatitis virus-induced hepatocellular carcinoma. Serum alpha-fetoprotein was elevated above normal (greater than or equal to 450 ng/ml) as early as 3 to 11 mo before terminal hepatocellular carcinoma in 11 of 16 of the woodchuck hepatitis virus-carrier woodchucks. In a pilot study, serum alpha-fetoprotein became markedly elevated above normal in woodchuck hepatitis virus-carrier woodchucks that developed hepatocellular carcinoma but not in serologically recovered or uninfected woodchucks (i.e., without hepatocellular carcinoma). Thus, alpha-fetoprotein may provide a useful noninvasive marker in the woodchuck model for detecting and monitoring woodchuck hepatitis virus-induced hepatocellular carcinoma from earlier stages.
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PMID:Alpha-fetoprotein in the woodchuck model of hepadnavirus infection and disease: immunochemical analysis of woodchuck alpha-fetoprotein and measurement in serum by quantitative monoclonal radioimmunoassay. 169 55

Circulating immune complexes (CIC), complement and alpha-fetoprotein (AFP) were detected in 93 hepatitis B surface antigen (HBsAg)-positive patients with hepatocellular carcinoma (HCC), 16 patients with liver cirrhosis (LC) and 54 healthy controls. The CIC and complements were significantly higher in HCC patients than in LC patients. The complement and polyethylene glycol(PEG)-CIC in HCC patients with LC were higher than those in LC only (P less than 0.0001). The complement levels in LC patients were significantly lower than in controls. There was no difference in C3 and C4 between HCC patients and controls, while the C3 proactivator was higher in HCC patients (P less than 0.02). The C1q-CIC was higher in HCC and LC patients when compared to controls (P less than 0.0001). In patients with HCC, there was no difference in the CIC and complement levels between patients with cirrhosis and those without. There were inverse correlations between C1q-CIC and C3 (P less than 0.05), C1q-CIC and C4 (P less than 0.04). The mean level of 3% PEG-CIC and C1q-CIC increased significantly as AFP elevated, but decreased as AFP was higher than 1599 ng/ml (P less than 0.05). These results imply that CIC increase with tumor growth but further tumor burden may result in a fall in CIC, there was a shifting of CIC from complement-fixing to non-complement-fixing as AFP increased gradually.
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PMID:Relationship of serum alpha-fetoprotein to circulating immune complexes and complements in patients with hepatitis B surface antigen-positive hepatocellular carcinoma. 169 50

The establishment of a new, differentiated, hepatitis B virus DNA-negative, human hepatoma cell line (named PLC/AN/2) is described. Neoplastic liver tissue was obtained during hepatectomy in an HBsAg-negative man. The established cell line is negative for alpha-fetoprotein and carcinoembryonic antigen; it has retained in vitro some of the differentiated functions of normal hepatocytes. Additionally, it presents a distinctive rearrangement (translocation) at the long arm of chromosome 4. The high degree of independence from serum growth factor requirements appears to be a major in vitro characteristic of PLC/AN/2 cells, making them a suitable model system for the more precise definition of the human hepatocellular carcinoma phenotype, including mechanisms of growth control.
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PMID:Growth-factor independence of a new differentiated hepatitis B virus DNA-negative human hepatoma cell line. 169 12

From 1980 to 1988, 161 patients underwent total extirpation of primary hepatocellular carcinoma. There were 18 operative or hospital deaths. Recurrence of tumor was diagnosed in 69 of the remaining 143 patients during follow-up treatment with monthly serum alpha-fetoprotein measurements and imaging studies that were performed every three months. There were 61 men and eight women whose ages ranged from 33 to 78 years. The histologic factors noted were cirrhosis of the liver in 60 patients and chronic hepatitis in nine. There were multiple or diffuse recurrences (Type A) in 34 instances, one to three nodular recurrences (Type B) in 21, marginal recurrences (Type C) in 11 and a mixed form of the latter two in three instances. Two-thirds of the recurrences were found within 1.5 years and the second peak was noted between 2.0 and 2.5 years. Sex of patient, hepatitis B virus, type of tumor, capsule, extent of hepatic resection and postoperative chemotherapy did not influence the rate of recurrence, but cirrhotic livers had a significantly higher recurrence rate. A second hepatic resection was performed upon 20 patients with a five year survival rate of 26.8 per cent. Good results were obtained by chemoembolization of the hepatic artery. Prevention and adequate treatment of intrahepatic recurrence are of paramount importance in achieving better surgical results for hepatocellular carcinoma.
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PMID:Assessment of pattern and treatment of intrahepatic recurrence after resection of hepatocellular carcinoma. 169 50


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