Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with liver cirrhosis undergoing portocaval shunt operation have been followed immunologically during their postoperative course regarding antibody titres to various antigens, viral as well as bacterial. The antibody determinations included rubella, vaccinia and cytomagalo viruses, diptheria toxoid, Candida albicans, streptolysin O, typhoid and paratyphoid O and H and the syphilis reactions: Kahn, Wassermann and Meinicke. Twenty-one blood donors served as controls. Skin test reactions to diptheria, Candida albicans, streptokinase and tuberculin were performed on the same patients. Eight patients submitted to cholecystectomy served as controls for pre-and postoperative skin tests and antibody titres. The liver cirrhosis group before operation had a significantly higher number of elevated antibody titres concomitant with a significantly reduced skin test reactivity to diphtheria toxoid and streptokinase. An increase in the number of elevated antibody titres was seen after portocaval shunt operation. In no case was a higher antibody titre associated with an increase in skin reactivity to the corresponding antigen. A number of significant titre changes to viral antigens were seen in the postoperative course without clinical evidence of the corresponding viral disease. Thes findings indicate that under certain circumstances antibody titre changes should be interpreted with caution.
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PMID:Antibody titre changes and skin reactivity in patients with liver cirrhosis undergoing portocaval shunt operation. 112 73

A high incidence of community-acquired hepatitis C virus infection that can lead to the progressive development of chronic active hepatitis, liver cirrhosis, and primary hepatocellular carcinoma occurs throughout the world. A vaccine to control the spread of this agent that represents a major cause of chronic liver disease is therefore needed. Seven chimpanzees (Pan troglodytes) have been immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)] that were copurified from HeLa cells infected with a recombinant vaccinia virus expression vector. Despite the induction of a weak humoral immune response to these viral glycoproteins in experimentally infected chimpanzees, a strong humoral immune response was obtained in all vaccines. The five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1. The remaining two vaccines became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections. These results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination.
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PMID:Vaccination of chimpanzees against infection by the hepatitis C virus. 750 68

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The absence of culture systems permissive for HCV replication has presented a major bottleneck to antiviral development. We sought to recapitulate the early steps in the life cycle of HCV by means of DNA-based expression of viral genomic sequences. Here we report expression of replicating HCV RNA by using a, to our knowledge, novel binary expression system in which cells were transfected with a T7 polymerase-driven full-length HCV cDNA plasmid containing a cis-acting hepatitis Delta ribozyme to control 3' cleavage, and infected with vaccinia-T7 polymerase. HCV genomic and replicative strand synthesis, in addition to protein synthesis, was detectable and depended on full-length HCV sequences. Moreover, the system was capable of generating HCV RNA quasispecies, consistent with the action of the low-fidelity HCV NS5B RNA polymerase. IFN-alpha, but not ribavirin, directly inhibited the viral replicative cycle in these cells, identifying the virus itself and not solely the immune system as a direct target of IFN action. The availability of a cell-based test for viral replication will facilitate screening of inhibitory compounds, analysis of IFN-resistance mechanisms, and analysis of virus-host cell interactions.
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PMID:Hepatitis C virus replication is directly inhibited by IFN-alpha in a full-length binary expression system. 1149 7

Historical sources for the use of Glycyrrhiza species include ancient manuscripts from China, India and Greece. They all mention its use for symptoms of viral respiratory tract infections and hepatitis. Randomized controlled trials confirmed that the Glycyrrhiza glabra derived compound glycyrrhizin and its derivatives reduced hepatocellular damage in chronic hepatitis B and C. In hepatitis C virus-induced cirrhosis the risk of hepatocellular carcinoma was reduced. Animal studies demonstrated a reduction of mortality and viral activity in herpes simplex virus encephalitis and influenza A virus pneumonia. In vitro studies revealed antiviral activity against HIV-1, SARS related coronavirus, respiratory syncytial virus, arboviruses, vaccinia virus and vesicular stomatitis virus. Mechanisms for antiviral activity of Glycyrrhiza spp. include reduced transport to the membrane and sialylation of hepatitis B virus surface antigen, reduction of membrane fluidity leading to inhibition of fusion of the viral membrane of HIV-1 with the cell, induction of interferon gamma in T-cells, inhibition of phosphorylating enzymes in vesicular stomatitis virus infection and reduction of viral latency. Future research needs to explore the potency of compounds derived from licorice in prevention and treatment of influenza A virus pneumonia and as an adjuvant treatment in patients infected with HIV resistant to antiretroviral drugs.
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PMID:Antiviral effects of Glycyrrhiza species. 1788 24

Chronic hepatitis C caused by infection with the hepatitis C virus(HCV)is a global health problem. HCV causes persistent infection that can lead to chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The therapeutic efficacy of antiviral drugs is not optimal in patients with chronic infection; furthermore, an effective vaccine has not yet been developed. To design an effective HCV vaccine, generation of a convenient animal model of HCV infection is necessary. Recently, we used the Cre/loxP switching system to generate an immunocompetent mouse model of HCV expression, thereby enabling the study of host immune responses against HCV proteins. At present vaccine has not yet been shown to be therapeutically effective against chronic HCV infection. We examined the therapeutic effects of a recombinant vaccinia virus(rVV)encoding HCV protein in a mouse model. we generated rVVs for 3 different HCV proteins and found that one of the recombinant viruses encoding a nonstructural protein(rVV-N25)resolved pathological chronic hepatitis C symptoms in the liver. We propose the possibility that rVV-N25 immunization has the potential for development of an effective therapeutic vaccine for HCV induced chronic hepatitis. The utilization of the therapeutic vaccine can protect progress to chronic hepatitis, and as a consequence, leads to eradication of hepatocellular carcinoma. In this paper, we summarized our current study for HCV therapeutic vaccine and review the vaccine development to date.
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PMID:[The development of therapeutic vaccine for hepatitis C virus]. 2306 54

A protective vaccine against hepatitis C virus (HCV) remains an unmet clinical need. HCV infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular cancer. Animal challenge experiments, immunogenetics studies, and assessment of host immunity during acute infection highlight the critical role that effective T cell immunity plays in viral control. In this first-in-man study, we have induced antiviral immunity with functional characteristics analogous to those associated with viral control in natural infection, and improved upon a vaccine based on adenoviral vectors alone. We assessed a heterologous prime-boost vaccination strategy based on a replicative defective simian adenoviral vector (ChAd3) and modified vaccinia Ankara (MVA) vector encoding the NS3, NS4, NS5A, and NS5B proteins of HCV genotype 1b. Analysis used single-cell mass cytometry and human leukocyte antigen class I peptide tetramer technology in healthy human volunteers. We show that HCV-specific T cells induced by ChAd3 are optimally boosted with MVA, and generate very high levels of both CD8(+) and CD4(+) HCV-specific T cells targeting multiple HCV antigens. Sustained memory and effector T cell populations are generated, and T cell memory evolved over time with improvement of quality (proliferation and polyfunctionality) after heterologous MVA boost. We have developed an HCV vaccine strategy, with durable, broad, sustained, and balanced T cell responses, characteristic of those associated with viral control, paving the way for the first efficacy studies of a prophylactic HCV vaccine.
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PMID:A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional HCV-specific T cell memory. 2537 45