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)

Infection by hepatitis C virus (HCV) generally induces an asymptomatic acute hepatitis. HCV infection becomes chronic in about 80% of cases. Chronic HCV infection is asymptomatic with persistent viremia and normal liver tests in a minority of the subjects. Chronic HCV infection is associated with chronic hepatitis with increased serum transaminases levels in the majority of the subjects. Among the patients with chronic hepatitis, the majority have minimal lesions; about 20% have a more severe disease and will develop after 5 to 20 years cirrhosis. In patients with cirrhosis, the incidence of hepatocellular carcinoma is high (around 5% per year). The factors influencing the evolution of HCV infection are not know. Alcohol is certainly an important factor. Virus related factors, such as genotype and level of replication, might also be important factors.
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PMID:[Natural history of hepatitis C virus infection]. 874 88

Hepatitis C virus (HCV) has been discovered in 1989 and is probably the most common cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma. HCV is a single-stranded, positive-sense RNA virus, 9.4 kilobases in length. The genetic organisation and the properties of viral proteins have been characterized. At least 50 HCV genotypes or subtypes have been identified. Genotypes 1, 2 and 3 are the most commonly observed in patients from Europe and USA. Genotype 1 is more resistant to interferon treatment. The hypervariability of HCV is responsible, within a single patient, of the existence of a spectrum of very closely-related genomes reffered as quasispecies that may be a mechanism of escape from the immune response and may explain chronicity. Virological diagnosis of HCV infection is based on the detection of anti-HCV antibodies by ELISA. In some cases (acute hepatitis, problems in the interpretation of ELISA tests, or in immunosuppressed patients), it is necessary to search for HCV RNA using genomic amplification or amplification of hybridization. These technics can also be useful to predict the response to interferon, as it has been demonstrated that patients with low viremia are better responders than others. HCV RNA detection or quantification could also be useful to follow the efficiency of anti-viral drugs.
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PMID:[Hepatitis C virus. Virological diagnosis]. 874 90

The viral load of hepatitis C virus, as reflected by hepatitis C virus viremia, has been shown to have important clinical implications. In this study the hepatitis C virus core protein level in serum was evaluated for the detection and quantification of hepatitis C virus viremia. Hepatitis C virus core protein in serum was detected using a simple and sensitive fluorescent enzyme immunoassay. Hepatitis C virus core protein was quantitated in 100 healthy subjects, 258 patients with hepatitis C virus infection and 108 patients with non-hepatitis-C-virus-related chronic liver diseases. HCV-RNA was determined using the branched DNA (bDNA) assay and reverse-transcription polymerase chain reaction. The detection limit of this fluorescent enzyme immunoassay was found between 10(4) - 10(5) copies/ml HCV-RNA equivalent. There was a good correlation between the core protein and bDNA assay results (p <0.01). Hepatitis C virus core protein was detected in 81% of patients with hepatitis C virus infection (acute hepatitis 4/5, chronic hepatitis 85/104, cirrhosis 64/73 and hepatocellular carcinoma 56/76) but in none of the healthy subjects and patients with non-hepatitis C virus chronic liver diseases. The amount of hepatitis C virus core protein in patients with hepatitis-C-virus-related hepatocellular carcinoma was lower compared to chronic hepatitis and cirrhosis (p <0.05). All 26 patients treated with interferon-alpha showed parallel changes between HCV-RNA and core protein levels. This fluorescent enzyme immunoassay is simple and quick (assay time <3 h) with sensitivity at least matching the bDNA assay. Similar levels of hepatitis C virus core protein were detected in patients with chronic hepatitis and cirrhosis, but patients with hepatocellular carcinoma tended to have a lower level of hepatitis C virus core protein.
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PMID:Simple fluorescent enzyme immunoassay for detection and quantification of hepatitis C viremia. 875 Jan 76

Chronic hepatitis C infection is associated with the rapid development of cirrhosis and hepatocellular carcinoma. A quantitative assay to determine the level of hepatitis C (HCV) viraemia during treatment would be useful in determining the effect of antiviral agents. Such an assay has been developed with the principle of the method being the co-amplification of the viral genome isolated from the patient with an RNA competitor molecule (CM) using the competitive reverse transcription-polymerase chain reaction (RT-PCR). Known amounts of the CM compete for amplification with HCV RNA from the patient. To quantify each sample, 5 amplification reactions with titrated amounts of CM were performed. The CM can be distinguished from the normal HCV PCR product since it has been genetically altered to be a smaller molecule by the process of restriction digestion, ligation and reamplification. This quantitative method was used to monitor the viral load in 10 patients undergoing antiviral therapy with lymphoblastoid interferon. The level of HCV viraemia in these patients ranged from 10(9) to 10(12) genomes/ml serum. Declines in the level of viraemia were seen in 8 of the 10 patients after therapy. Since patients with low HCV viraemia levels are more likely to respond to interferon therapy in a sustained fashion, this method may also be employed to quantitate the level of viraemia in patients prior to interferon treatment, and may be an indicator of the dose and schedule of treatment. These results show that this quantitative method is useful in the monitoring of HCV viral load in patients.
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PMID:Quantitation of hepatitis C viraemia by a competitive reverse transcription-polymerase chain reaction system. 877 56

Recently, a novel virus, tentatively designated GB virus (GBV-C) was identified in patients with hepatitis. The frequency of this novel virus infection was therefore investigated in 58 patients with chronic hepatitis B virus (HBV) infection and in 74 patients with chronic hepatitis C virus (HCV) infection who had received orthotopic liver transplantation (OLT) because of decompensated liver cirrhosis. Before OLT, GBV-C sequences were found by reverse transcription nested polymerase chain reaction with primers derived from the helicase-like region in six (10%) of the HBV- and in six (8%) of the HCV-infected patients. Specificity of the polymerase chain reaction products was confirmed in eight of them by direct sequencing. Pretransplant GBV-6 viremia was associated with posttransplant viremia in 75% of patients. The comparison of GBV-C nucleotide and amino acid sequences within the helicase-like region revealed that pre- and posttransplant sequences differed only in 0-7 nucleotide exchanges, and with the exception of one, all of them were silent mutations. After OLT, 29% of the HBV- infected and 12% of the HCV-infected patients became GBV-C positive,indicating a high rate of "de novo" GBV-C infection. By correlating the GBV-C status with the frequency of the occurrence of graft hepatitis in both groups of patients, it became evident that posttransplant GBV-C viremia did not increase the risk for this clinical condition. However, we found a significantly higher percentage of hepatocellular carcinoma in patients with pre-OLT GBV-C/HCV coinfection compared with patients with HCV infection alone (5/6 vs. 16/68;P<0.01).
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PMID:GB virus C infection in patients with chronic hepatitis B and C before and after liver transplantation. 882 65

beta-L-Nucleoside analogs represent a new class of potent antiviral agents with low cytotoxicity which provide new hope in the therapy of chronic hepatitis B virus (HBV) infections. We evaluated the anti-HBV activity of 2',3'-dideoxy-beta-L-5-fluorocytidine (beta-L-F-ddC), a beta-L-nucleoside analog derived from 2',3'-dideoxycytidine (ddC), in the duck HBV (DHBV) model. This compound was previously shown to inhibit HBV DNA synthesis in a stably transfected hepatoma cell line (F2215). Using a cell-free system for the expression of an enzymatically active DHBV polymerase, we could demonstrate that the triphosphate form of beta-L-F-ddC does inhibit hepadnavirus reverse transcription. In primary duck hepatocyte culture, beta-L-F-ddC showed a potent inhibitory effect on DHBV DNA synthesis which was concentration dependent. Although beta-L-F-ddC was shown to be less active than ddC against the DHBV reverse transcriptase in vitro, beta-L-F-ddC was a stronger inhibitor in hepatocytes. The oral administration of beta-L-F-ddC in experimentally infected ducklings showed that beta-L-F-ddC is a potent inhibitor of viral replication in vivo. Short-term therapy could not prevent a rebound of viral replication after the drug was withdrawn. Preventive therapy with beta-L-F-ddC could delay the onset of viremia by only 1 day compared with the time to the onset of viremia in the control group. The in vivo inhibitory effect of beta-L-F-ddC was much stronger than that of ddC and was not associated with signs of toxicity. Our data show that beta-L-F-ddC inhibits hepadnavirus reverse transcription and is a strong inhibitor of viral replication both in vitro and in vivo.
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PMID:2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo. 883 96

Hepatitis B virus (HBV) has long been known to be the major etiologic factor of chronic liver diseases and hepatocellular carcinoma (HCC), and in Taiwan 80-90% of chronic liver diseases and HCC are caused by HBV. Assays for antibody to hepatitis C virus (HCV) and to detect its viral genome (HCV-RNA) have revealed HCV as the next most common cause of these diseases in Taiwan. The prevalence of antibody to HCV (anti-HCV) in hepatitis B surface antigen (HBsAg)-negative patients is around 70-80%, and most of the patients are viremic. Anti-HCV is found in 0.5-1.0% of healthy adults. The epidemiology of HCV infection in Taiwan is similar to other areas of the world, with horizontal transmission as the major route of infection. Blood transfusion was an important route of transmission, accounting for 30-40% of chronic HCV infection. After screening for anti-HCV in blood donors was instituted, this infection route was effectively controlled. The nucleotide sequences of a Taiwanese isolate of HCV are similar to Japanese isolates (homology of > 90%) and less similar to the prototype U.S. isolate (78% homology). The predominant genotype is type II/lb, being detected in 66-71% of patients with chronic hepatitis C and in 83% of those with cirrhosis or HCC. Analysis of serum HCV cDNA levels by competitive polymerase chain reaction showed that the levels ranged from 10(1) to 10(7) copies/ml and did not correlate with the gender of the patients, past blood transfusion, serum aminotransferase activities, or histologic severity. However, the serum HCV levels were higher in patients with genotype II/lb than those with type III/2a or type IV/2b (p < 0.005), indicating genotype as an important determinant of levels of HCV viremia. Mixed infections of multiple genotypes of HCV may contribute to the acute exacerbations of chronic hepatitis C; among 20 patients with exacerbations, 11 (55%) had evidence indicating the emergence of a different predominant HCV genotype; among 26 without exacerbations, this was found in only 2 (8%) (p < 0.005). The incidence of HCC was studied by prospective follow-up of patients with cirrhosis by regular hepatic ultrasound examinations and serum alpha-fetoprotein surveillance in the following four groups: i) HBsAg-positive, 300 patients; ii) anti-HCV positive, 151 patients; iii) both positive, 144 patients; and iv) both negative, 62 patients. Each year, 3-5% developed HCC, and the difference in incidence between the four groups was not statistically significant. The mean age when HCC was detected was 56 +/- 10, 63 +/- 9, 55 +/- 11 and 60 +/- 14 years in each group, respectively. The results indicate a high incidence of HCC in cirrhotic patients in Taiwan, whether the cirrhosis was related to HBV or HCV; dual infections of both viruses did not accelerate the occurrence of HCC. Although most anti-HCV-positive patients with HCCs had cirrhosis, HCC did occur in some patients without cirrhosis. Studies of these two groups of HBsAg-negative, anti-HCV-positive HCC patients revealed less frequent detection of HCV-RNA in serum and lower titers of HCV RNA in HCC without cirrhosis. In fact, 10/20 (50%) non-cirrhotic HCC patients were actually positive for serum HBV DNA by PCR, indicating the possible role of HBV in the etiology of HCC in these patients.
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PMID:Hepatitis C virus in chronic liver disease and hepatocellular carcinoma in Taiwan. 887 6

We investigated the presence of hepatitis C virus (HCV) infection in 58 patients with humoral immunodeficiencies. Forty-three of these patients had common variable immunodeficiency (CVI), 2 had sporadic hyperimmunoglobulin M (HIM) syndrome, 2 had immunoglobulin G subclass deficiency, 4 had ataxia-telangiectasia (AT), and 7 had X-linked agammaglobulinemia (XLA). Patients with late-onset hypogammaglobulinemia (those with CVI, HIM, or immunoglobulin G subclass deficiency) had a 38.2% prevalence of HCV infection. In patients with XLA or AT, HCV infection was not detectable. Most of the HCV-infected patients had persistent viremia, with histologic findings of chronic hepatitis. Although patients positive for HCV ribonucleic acid (RNA) had received several lots of immunoglobulin, we were unable to detect any correlation between the time that alanine aminotransferase levels increased and the time that intravenous immunoglobulin therapy was given, except in one patient with CVI. Moreover, we found no differences in the number of blood transfusions, surgical procedures, or administrations of intravenous or intramuscular immunoglobulin between HCV RNA-positive and HCV RNA-negative groups. We concluded that: (1) the incidence of HCV infection in patients with hypogammaglobulinemia is much higher than that reported in the Italian general population; (2) although patients with hypogammaglobulinemia have persistent viremia, they do not show an aggressive course of HCV disease, nor does hepatocarcinoma develop; and (3) intravenous immunoglobulins are only one of several possible causes of HCV transmission in patients with humoral immunodeficiencies.
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PMID:Hepatitis C virus infection in Italian patients with hypogammaglobulinemia. 893 Apr 47

A routine screening test used in the diagnosis of hepatitis C virus (HCV) infection is the anti-HCV antibody (anti-HCV) test containing core, NS3, NS4, and NS5 antigens of HCV. When HCV infection occurs in immunocompromised hosts, antibody formation against core, NS3, or NS4 antigens may be weak in the presence of HCV viremia and cannot be detected by routine anti-HCV tests. This study proposed that in immunocompromised hosts such as patients with chronic renal failure (whose capacity to form antibodies is diminished), antibody formation against the E2 region would be preserved, because the E2/NS1 region of HCV is strongly immunogenic. The aim of this study is to evaluate the significance of anti-E2 in the diagnosis of HCV infection among patients on maintenance hemodialysis who are anti-HCV-negative, using a conventional third-generation enzyme immunoassay (EIA) kit. The E2/NS1 gene of HCV encoding the amino acid sequence 388-664 was molecularly cloned into a vector containing an SV 40 promotor and was expressed in Chinese Hamster ovary cells. Using this E2 protein, the anti-E2 test was performed by EIA on 100 patients on maintenance hemodialysis, and on 50 patients with chronic hepatitis C who were anti-HCV-positive, to evaluate the antigenecity of the E2 protein. Of the 100 hemodialysis patients, 15 (15.0%) tested anti-HCV-positive using a third generation anti-HCV ELISA kit. Of the 85 patients who tested negative for anti-HCV, nine (10.6%) were anti-E2-positive and six (66.7%) of these anti-E2 positive patients showed HCV RNA viremia by HCV reverse transcription-polymerase chain reaction. Fourty-two (84.0%) of 50 patients with chronic hepatitis C were anti-E2-positive. As a control group, we tested for anti-E2 among 30 blood donors who were anti-HCV-negative, and also among 85 patients with hepatocellular carcinoma who were anti-HCV-negative, but in both groups, none (0%) was anti-E2-positive. In conclusion, these data suggest that the E2 protein of HCV should be included in a diagnostic anti-HCV kit for the detection of HCV infection in immunocompromised patients.
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PMID:Significance of anti-E2 in the diagnosis of HCV infection in patients on maintenance hemodialysis: anti-E2 is frequently detected among anti-HCV antibody-negative patients. 895 33

Hepatitis C is becoming the main cause of cirrhosis and primary liver carcinoma. Infection by hepatitis C virus (HCV) generally induces an asymptomatic acute hepatitis. HCV infection becomes chronic in about 80% of cases. In a minority of the subjects, chronic HCV infection is asymptomatic with persistent viremia and normal liver tests. These asymptomatic subjects have minimal liver histologic lesions and a good prognosis. In a majority of the subjects, chronic HCV infection is associated with chronic hepatitis with increased serum transaminases levels. Among the patients with chronic hepatitis, the majority have a mild liver disease with a moderate increase in serum transaminases levels and, at liver histology, minimal lesions; a minority (about 20%) have a more severe liver disease and will develop cirrhosis after 5 to 20 years. In patients with HCV related cirrhosis, the incidence of hepatocellular carcinoma is high (around 5% per year). The factors influencing the evolution of HCV infection are not known. Alcohol is certainly an important factor which increases the risk of development of fibrosis then cirrhosis. Virus related factors, such as genotype and level of replication, might also be important. Autoimmune diseases have been reported in association with hepatitis C. HCV infection is a major cause of mixed cryoglobulinemia associated with vasculitis or glomerulonephritis. A relationship between HCV and auto-immune diseases such as thyroiditis or Gougerot syndrome has been suggested but not demonstrated. HCV infection is frequent in patients with porphyria cutanea tarda; in these patients, HCV related liver disease might trigger the expression of the metabolic disease.
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PMID:[Clinical picture and evolution of hepatitis C]. 899 8


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