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

Human alcoholics have reduced neuronal counts in certain brain regions, such as superior frontal cortex (SFC), where the form and quantity of synaptic gamma-aminobutyric acid type A (GABAA) receptor sites are atypical. We measured the expression of GABAA receptor isoform mRNA and protein, since GABAA receptor pharmacology is strongly influenced by its subunit composition. Cortex samples were obtained at autopsy; whole-tissue extracts were assayed for mRNA by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), while synaptic membranes were studied for both GABAA receptor pharmacology and subunit protein levels by Western blots with isoform-specific antibodies. Although alpha 1 and alpha 3 mRNA species were strongly expressed in alcoholics irrespective of cirrhosis than in controls, alpha 1 protein differed little between case groups, and alpha 3 protein showed some complex variations. Differences in GABAA pharmacology conformed more closely with differences in protein levels than with altered mRNA expression.
 ...
PMID:Cell death mediated by amino acid transmitter receptors in human alcoholic brain damage: conflicts in the evidence. 966 64

The diagnosis of cirrhosis in patients with hepatitis C virus (HCV) infection is currently made using a liver biopsy. In this study we have trained and validated artificial neural networks (ANN) with routine clinical host and viral parameters to predict the presence or absence of cirrhosis in patients with chronic HCV infection and assessed and interpreted the role of the different inputs on the ANN classification. Fifteen routine clinical and virological factors were collated from 112 patients who were HCV RNA positive by reverse transcriptase-polymerase chain reaction (RT-PCR). Standard and Ward-type feed-forward fully-connected ANN analyses were carried out both by training the networks with data from 82 patients and subsequently testing with data from 30 patients plus performing leave-one-out tests for the whole patient data set. The ANN results were also compared with those from multiple logistic regression. The performance of both ANN methods was superior compared with the logistic regression. The best performance was obtained with the Ward-type ANNs resulting in a sensitivity of 92% and a specificity of 98.9% together with a predictive value of a positive test of 95% and a predictive value of a negative test of 97% in the leave-one-out test. Hence, further validation of the ANN analysis is likely to provide a non-invasive test for diagnosing cirrhosis in HCV-infected patients.
 ...
PMID:Prediction of cirrhosis in patients with chronic hepatitis C infection by artificial neural network analysis of virus and clinical factors. 975 Oct 12

Sustained responses to interferon-alpha occur in 10% to 25% of patients with chronic hepatitis C, but the long-term outcome is not well defined. We evaluated the long-term clinical, histological, and virological outcomes of 10 patients with chronic hepatitis C who were treated between 1984 and 1987 with interferon-alpha-2b for 52 +/- 6 weeks (total doses of 492 +/- 116 MU). Before therapy, all 10 had hepatitis C virus (HCV) RNA, elevations of serum aminotransferases, and chronic hepatitis with fibrosis on liver biopsy. Clinical follow up was 6 to 13 years, and liver biopsies were done 5 to 11 years after initiation of therapy. HCV RNA was assayed by qualitative and quantitative reverse transcriptase-polymerase chain reaction assays. Among 5 patients who had a 6-month sustained response after therapy, all remained HCV RNA negative, and at last follow-up, 4 had normal and 1 minimally elevated serum aminotransferase levels. Liver biopsy specimens were nonreactive for HCV RNA, and all the patients showed improvements in both inflammation and fibrosis and were either normal or had mild, nonspecific inflammatory changes. Among 5 patients without a sustained response, all continued to have HCV RNA in serum and persistent or intermittent aminotransferase elevations. Liver biopsy specimens showed little or no change in necrosis and inflammation; all except 1 patient had progression of fibrosis scores or cirrhosis. All 5 patients had symptoms of chronic hepatitis, 1 underwent liver transplantation, and another had progressive hepatic decompensation. In conclusion, patients with a 6-month posttreatment virological response have a favorable long-term clinical and histological outcome.
 ...
PMID:10-Year follow-up after interferon-alpha therapy for chronic hepatitis C. 975 52

Triple antiretroviral therapy combining reverse transcriptase and protease inhibitors modifies the prognosis of human immunodeficiency virus (HIV) infection, with dramatic improvement in immune status. The precise impact, if any, of anti-HIV triple therapy on hepatitis C virus (HCV) infection is unknown. We describe an unusual case of rapidly evolving HCV-related cirrhosis that paralleled restoration of immune status in an HIV-infected patient and discuss the possible link between such a severe course of hepatitis C and anti-HIV triple therapy.
 ...
PMID:Rapidly evolving hepatitis C virus-related cirrhosis in a human immunodeficiency virus-infected patient receiving triple antiretroviral therapy. 982 79

Telomerase is a specialized type of reverse transcriptase that catalyzes the synthesis and extension of telomeric DNA. High levels of telomerase activity have been detected in most hepatocellular carcinoma (HCC) tissues; very weak telomerase activity is, however, detected in approximately half of nontumorous chronic liver disease tissues. The purpose of this study was to investigate the possible source of this weak telomerase activity in these tissues using quantitative competitive reverse transcription (RT)-polymerase chain reaction (PCR) and in situ RT-PCR. Competitive RT-PCR indicated that the relative amount of human telomerase RNA (hTR) was significantly higher in chronic hepatitis or liver cirrhosis compared with the normal liver (p < 0.005), and in HCC compared with the normal liver (p < 0.001) and with chronic hepatitis or liver cirrhosis (p < 0.0001). In the normal liver tissue, hTR was detected by in situ RT-PCR in occasional sinusoidal cells and nuclei of occasional hepatocytes. In tumor-free liver or tumor-bearing liver, hTR was detected in sinusoidal cells, infiltrating lymphocytes, occasional proliferative bile ductal epithelial cells, and the nuclei of occasional hepatocytes. In HCC, hTR was detected in nuclei of all HCC cells as an intense signal and in sinusoidal cells. These results indicate that the amount of hTR increases in the nuclei of hepatocytes during hepatocarcinogenesis, and that the cells associated with the weak telomerase activity in approximately half of the nontumorous chronic liver lesions are mainly migrating lymphocytes and sinusoidal cells.
 ...
PMID:Quantitative analysis and in situ localization of human telomerase RNA in chronic liver disease and hepatocellular carcinoma. 995 7

The sequential development of cirrhosis and hepatocellular carcinoma (HCC) in patients with post-transfusion hepatitis was a clue that led to the identification of hepatitis C virus (HCV) as a risk factor for HCC. The average time lag between transfusion-associated infection and cancer development was 30 years, with a range of 15-45 years. Using the polymerase chain reaction (PCR) technique, HCV-RNA has been almost invariably detected in serum and tumor tissue of anti-HCV-seropositive patients with HCC In many patients, HCV-RNA was found to belong to the more pathogenic type 1b. However, it is unlikely that HCV plays a direct role in liver tumorigenesis, since no reverse transcriptase activity has been found in infected livers. One current opinion is that HCV may promote cancer through cirrhosis, which is per se an important risk factor for this tumor: almost all patients with HCC have cirrhosis and up to 30% of them have coexisting serological evidence of hepatitis B virus (HBV) or alcohol abuse, further supporting the idea that both HCC and cirrhosis might result from the interplay of several risk factors. However, there are also data suggesting that HCV may interact with cellular genes regulating cell growth and differentiation independently of the onset of cirrhosis.
 ...
PMID:The role of hepatitis C virus in hepatocellular carcinoma. 1002 14

Several new nucleoside analogues have been developed which can inhibit hepatitis B replication by at least two logs. Lamivudine is the most widely studied of these new agents. Extensive phase II and III studies in patients with chronic hepatitis B have been completed. The sustained HBeAg seroconversion rate in patients who have received 100 mg lamivudine increases from 17% after a year of treatment to 27% after 2 years of treatment. Histological improvement has been noted in 38%-52% of lamivudine-treated patients, exceeding the improvement seen in placebo recipients. Similar histological improvement has been noted in anti-HBe-positive, DNA- positive patients. Lamivudine can prevent recurrence of hepatitis B after liver transplantation. It is likely that in the absence of immune clearance to accelerate elimination of infected hepatocytes, inhibitors of virus replication such as lamivudine will need to be administered for a long period to reduce the burden of infected hepatocytes in the liver, and to prevent relapse. The drug is generally well tolerated with few direct adverse events. Genotypic mutations have been observed in 23% (range 13-32%). In a study in Asian patients treated for two years the incidence of these mutants increased to 38% (as detected by PCR). Loss of susceptibility to lamivudine has been found to be due to reverse transcriptase amino acid substitutions. Lamivudine is likely to be reserved for patients with replicative hepatitis B infection with active chronic hepatitis, and/or active cirrhosis. Copyright 1998 John Wiley & Sons, Ltd.
 ...
PMID:Lamivudine treatment of chronic hepatitis B. 1039 3

Hepatitis C virus (HCV) is pathogenetically involved in many cases of hepatocellular carcinoma (HCC) worldwide. HCV-related HCC is on the rise in many developed countries as a consequence of past infections with HCV. The time lag between HCV infection and cancer development is several decades. HCV-related tumors arise in older patients, are almost invariably associated with cirrhosis, and often have a less aggressive course than HCC related to other etiologic factors. In most patients, HCC grows as a single hepatic node for years before generating satellite or distant tumor nodes. However, there are tumors that originate as multifocal disease. Tumor progression and hepatic failure are the leading causes of death in most patients. HCV has been almost invariably detected in tumor tissue of anti-HCV patients with HCV, but it is not clear whether the virus promotes cancer through chronic hepatocellular inflammation, which is per se an important risk factor for HCC, or has a direct role in liver carcinogenesis. No reverse transcriptase activity has been found in infected livers, but there are data suggesting that HCV has oncogenic properties, because its interacts with cellular genes regulating cell growth and differentiation.
 ...
PMID:Hepatitis C virus and hepatocellular carcinoma. 1051 6

Hepatitis B virus (HBV) infection is a worldwide public health problem. In France, 150,000 individuals are infected with the HBV. Although many are asymptomatic carriers, about 30% have chronic hepatitis, a condition associated with a risk of cirrhosis and hepatocellular carcinoma. Antiviral treatments, most notably interferon alpha, probably modify the natural history of hepatitis B, decreasing the risk of hepatocellular carcinoma and increasing survival. Nucleoside analogs, particularly lamivudine, have also demonstrated potent antiviral activity, which should however be weighed against the increasing risk over time of mutation development in the YMDD region of the DNA polymerase reverse transcriptase. Antiviral therapy monitoring should include clinical safety evaluations and periodic laboratory tests including blood cell counts, transaminase activities, and serum DNA levels. The improving results provided by antiviral drugs should not deflect attention away from the importance of large-scale hepatitis B immunization of neonates, which has been shown to decrease the incidence of hepatocellular carcinoma in areas with high levels of hepatitis B endemicity.
 ...
PMID:[Hepatitis B: epidemiology, natural history, biology, treatment monitoring]. 1060 72

Generally, 0.4-2.5% of patients with chronic hepatitis C virus (HCV) infection develop hepatocellular carcinoma (HCC). HCC occurs more often in patients with cirrhosis and in those with increased liver cell proliferation. HCV-related tumors occur in older patients and often have a less aggressive course than HCC, related to other etiological factors. Many HCV-related HCC are multifocal in origin. However, many tumors grow as a single hepatic nodule for years before generating satellite or distant tumor nodules. The growth pattern varies from one tumor to another, with tumor volume doubling times ranging from 1 to 20 months. Tumor progression and hepatic failure are the leading causes of death in most patients. Using the polymerase chain reaction technique, HCV-RNA has been almost invariably detected in serum and tumor tissue of anti-HCV patients with HCC. In many patients, HCV-RNA was found to belong to the possibly more pathogenic type 1b. However, it is unlikely that HCV plays a direct role in liver tumorogenesis, since no reverse transcriptase activity has been found in infected livers. One current opinion is that HCV may promote cancer through cirrhosis, which is per se an important risk factor for this tumor. In HCV carriers, the risk of developing HCC and having more severe tumor disease may be increased by coexisting hepatitis B virus (HBV) or alcohol abuse, further supporting the idea that both HCC and cirrhosis might be a result of the interplay of several risk factors. HCC could also be the consequence of HCV interacting with cellular genes that regulate cell growth and differentiation, independent of the effect of cirrhosis.
 ...
PMID:Natural history and pathogenesis of hepatitis C virus related hepatocellular carcinoma. 1062 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>