Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the influence of chronic hepatitis on intercellular adhesion molecule-1 serum concentration, we measured intercellular adhesion molecule-1 in the serum of 84 patients with chronic liver disease (17 chronic persistent hepatitis, 42 chronic active hepatitis and 25 active cirrhosis) caused by hepatitis B virus (n = 46), hepatitis C virus (n = 10) and autoimmunity (n = 28). Furthermore, 20 patients with acute viral hepatitis (16 hepatitis B virus and 4 hepatitis A virus) and 6 patients with acute drug-induced hepatitis were included. Sera from 20 healthy persons were used as control. Follow-up examinations were performed during immunosuppressive therapy in 20 patients with autoimmune chronic liver disease (13 chronic active hepatitis and 7 active cirrhosis). Intercellular adhesion molecule-1 serum concentration was significantly increased in patients with acute viral hepatitis, drug-induced hepatitis, chronic active hepatitis and active cirrhosis compared with healthy controls and with patients with chronic persistent hepatitis. Intercellular adhesion molecule-1 was also significantly increased in severe chronic active hepatitis and active cirrhosis compared with moderate chronic active hepatitis and moderate active cirrhosis. Serum concentration of intercellular adhesion molecule-1 decreased significantly in patients with autoimmune chronic liver disease after 2 mo of immunosuppression when remission was present. A close correlation between aspartate aminotransferase and intercellular adhesion molecule-1 serum levels was found. We conclude the following: (a) in chronic liver disease intercellular adhesion molecule-1 serum concentration may represent, at least in part, hepatocellular damage; and (b) intercellular adhesion molecule-1 serum level does not differentiate between chronic autoimmune and chronic viral hepatitis.
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PMID:Intercellular adhesion molecule-1 concentration in sera of patients with acute and chronic liver disease: relationship to disease activity and cirrhosis. 810 56

Ursodeoxycholic acid (UDCA or ursodiol) administration has been associated with a reduction of serum liver enzymes in patients with chronic liver disease and with improvement of liver histology in patients with primary biliary cirrhosis. To establish the potential therapeutic efficacy of ursodiol in chronic hepatitis, serum biochemistry and liver histology were investigated in a multicenter, double-blind placebo controlled clinical trial. Sixty patients with non-cholestatic chronic active (mild or severe) hepatitis, mainly of viral (virus C) etiology and almost completely asymptomatic, were enrolled in 3 centers: 29 were assigned to receive placebo and 31 UDCA (600 mg/day) for 1 year. Demographic, biochemical, virological and histological features were balanced between the 2 groups at the entrance into the study. Fifty-six patients (34 males, 22 females; 19 with cirrhosis; 5 HBsAg-positive; 45 anti-HCV positive) were included in the final analysis. Compliance was checked by measuring UDCA levels at the 3 follow-up visits (3, 6 and 12 months). Liver biopsy was performed at the beginning and at the end of treatment and was evaluated blindly by our pathologist (F.C.). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyltransferase (GGT) levels were significantly reduced by 25% from baseline values during treatment with ursodiol but not with placebo. The efficacy of UDCA in lowering serum AST and ALT was more pronounced in the presence of cirrhosis. The semiquantitative liver histological score used remained substantially unchanged after treatment and no differences between placebo and UDCA were found for portal or periportal necrosis or inflammation, intralobular degeneration, cholestasis or fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ursodiol in the long-term treatment of chronic hepatitis: a double-blind multicenter clinical trial. 815 Nov 7

This study was carried out to evaluated the role of the fibronectin (FN) in chronic liver diseases. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease. For these reasons FN plasmatic concentration was assayed in patient with different degrees of chronic liver disease; the correlation between FN and the most common parameters of liver function was also evaluated. Moreover we also correlated FN plasma levels with laminin and the N-terminale peptide of type III procollagen, serum levels, that are through to be markers of fibrogenesis. 172 patients were studied: twenty-one patients suffering from chronic persistent hepatitis (CPH), 45 from chronic active hepatitis (CAH) and 106 from liver cirrhosis (LC). Last patients were also divided according the Child-Pugh's classification. Control group was composed of 74 healthy blood donors. Significant reduction of plasmatic levels of FN was found in the LC groups in comparison with control group (p < 0.0001) and also with CPH group (p < 0.01) and with CAH group (p < 0.0001). Lower values of FN were found in the LC group at advanced stage (Child-Pugh's B and C classes). In the group of CAH significant correlations with the parameters of cholestasis (GGT, APh, Tot. Bil. p < 0.005) were found, while in the group of LC significant correlations both with the parameters of synthesis (Alb. and Protr. time p < 0.01) and necrosis (AST/ALT p < 0.001). A negative correlation was also found between FN and spleen volume (p < 0.05). No correlation between FN and the parameters of fibrosis was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Plasma fibronectin in chronic liver diseases]. 821 Jun 24

The proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha are thought to play important roles in the pathophysiology of liver disease. Specific antagonists of these cytokines have been found in recent years. Interleukin-1 receptor antagonist is a specific interleukin-1 antagonist. The soluble receptor derived from the cell-surface p55 tumor necrosis factor receptor p55 is a naturally occurring substance that inhibits the biological effects of tumor necrosis factor. We used specific radioimmunoassays to detect circulating interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor p55 levels in 14 patients with acute viral hepatitis and in 160 patients with various chronic liver diseases. Levels of interleukin-1 receptor antagonist and, especially, tumor necrosis factor soluble receptor were markedly increased in most patients with chronic liver disease regardless of pathogenesis and in viral hepatitis. Patients with chronic liver disease and cirrhosis showed significantly higher levels of both cytokine antagonists than did noncirrhotic patients. Correlations between interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor were more significant than those of either antagonist with C-reactive protein or blood sedimentation rate. Interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor levels were also positively correlated with bilirubin and AST levels. We conclude that circulating levels of interleukin-1 receptor antagonist and tumor necrosis factor soluble receptor may reflect ongoing disease activity and probably modulate some effects of endogenous interleukin-1 and tumor necrosis factor.
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PMID:Circulating interleukin-1 and tumor necrosis factor antagonists in liver disease. 822 19

Several biochemical events accompany and mediate the development of chronic liver disease and its evolution into cancer. Low plasma zinc and high copper levels have been observed in various liver diseases, such as liver cirrhosis and viral hepatitis, while increased oestradiol levels have been documented in chronic liver damage and hepatocellular carcinoma. We administered CCL4 intragastrically to 10 female Sprague Dawley rats for 30 weeks. All animals developed cirrhosis and four also developed hepatocellular carcinoma. Plasma levels of zinc, copper and oestradiol were significantly higher in the latter group than in animals with simple cirrhosis. Progesterone, AST and bilirubin showed a trend toward significant differences whereas testosterone and ALP levels were unchanged. These findings add to the evidence that sex hormones and trace elements are involved in the process of the development of chronic liver damage and carcinogenesis.
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PMID:Sex hormones and trace elements in rat CCL4-induced cirrhosis and hepatocellular carcinoma. 835 89

Molecules governing cellular interactions have been suggested to be involved in the spurious elevation of alpha 1-fetoprotein (AFP) in non-neoplastic liver disease. To explore this controversial issue, we measured AFP, circulating intercellular adhesion molecule 1 (cICAM-1), and common liver function tests in 111 patients (71 male, 40 female). Eighty-four patients had non-neoplastic chronic liver disease and 27 had hepatocellular carcinoma. The concentration of cICAM-1 was determined immunoenzymatically. In patients with non-neoplastic chronic liver disease, univariate analysis demonstrated a significant correlation between AFP and cholinesterase (R = -0.397, P < 0.001), aspartate aminotransferase (R = 0.421, P < 0.001), bilirubin (R = 0.231, P < 0.05) and cICAM-1 (R = 0.430, P < 0.001). Multivariate analysis among these variables and AFP indicated cICAM-1 to be the strongest independent predictor of AFP. We conclude that cICAM-1 compares favourably with liver function tests in predicting non-specific AFP variations in non-neoplastic chronic liver disease, suggesting a link between targeting of the inflammatory damage to the hepatocyte and development of neoplasia.
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PMID:Circulating intercellular adhesion molecule 1 predicts non-specific elevation of alpha 1-fetoprotein. 864 48

We describe a series of studies on the contribution of laboratory medicine to the differential diagnosis of clinically confounding diseases in the field of chronic hepatobiliary diseases. Ascitic cholesterol and lactate dehydrogenase (LD), selected by multivariate discriminant analysis (MDA) from a multitude of serum and ascitic analytes, correctly classified 100% of patients with malignant ascites or non-malignant ascites. In addition, ascitic pseudouridine differentiated hepatocarcinoma (HC) from cirrhotic ascites with a diagnostic effectiveness (overall discrimination power) of 90%. A panel of analytes constituted by serum gamma-glutamyltransferase (GGT), the GGT isoenzyme complexed with low- and very low-density lipoprotein, aspartate aminotransferase, copper, hepatic alkaline phosphatase (AP), the LD-5 isoenzyme and alpha-fetoprotein (AFP), selected by the MDA, correctly classified 93% of about 200 cases of cirrhosis or HC. Finally, MDA also identified an equation, based on serum values of the LD-4/LD-5 and carcinoembryonic antigen/AFP ratios, AP and iron that correctly classified 96% of HC or secondary liver neoplasia cases in 100 patients. This approach based on panels of analytes selected by a sophisticated statistical analysis is a rapid and non-invasive contribution to the differential diagnosis of chronic liver disease including neoplasia.
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PMID:Multivariate discriminant analysis of biochemical parameters for the differentiation of clinically confounding liver diseases. 902 25

In order to evaluate the pathogenetic role of iron in Porphyria cutanea tarda (PCT), the metabolism of iron was studied in 440 patient with PCT and associated chronic liver disease (CLD) and in 91 nonporphyric CLD patients (used as a control group). The parameters considered were the following: serum iron, ferritin, Total Iron Binding Capacity (TIBC) and percent saturation of transferrin. The statistical analysis showed that the differences between the means, in the two groups, were not significant in any of the parameters examined. To investigate the possible relationships between iron metabolism and other chemico-clinical parameters concerning the porphyric disease, the associated hepatic disease and hemometry, we studied the correlations between iron parameters and total urinary and serum porphyrins, serum copper, serum albumin, hemoglobin, red blood cells, ALT, AST, CHE and GLDH. This investigation was only possible in the last 99 cases. In addition to the obvious correlations between the parameters concerning iron metabolism, the highly significant (p < 0.001) correlation between ferritin and enzyme activities which indicate cytolysis (ALT, AST, GLDH) is extremely interesting. The results seem to point to the tentative conclusion that the alterations of iron metabolism are more related to the hepatocellular necrosis than to the metabolism of porphyrins.
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PMID:Iron and porphyria cutanea tarda. 907 91

Hepatitis C virus is the leading cause of acute and chronic liver disease in hemodialysis patients. There are at least six major HCV-genotypes, with a well documented geographical distribution in the general population. Moreover, HCV-genotype is one of the major determinants of the therapeutic response to Interferon Alpha in affected patients. Since the therapeutic outcome in HCV-positive hemodialysis patients, especially with regard to the different HCV-genotypes, is of interest, a multicentre epidemiologic study was performed in HCV-antibody positive hemodialysis patients of two geographically remote countries, i.e. in Flanders (Belgium) and in Saudi-Arabia. 184 chronic hemodialysis patients, with a positive second or third generation Elisa assay for HCV, were tested for HCV-viremia and HCV-genotype, using a 5' untranslated region (UR) nested PCR for the detection of HCV-RNA and subsequently type-specific probes to hybridize with HCV-RNA (Inno-Lipa). Additionally, clinical data were collected by means of a standardized questionnaire, thoroughly completed by the nephrologist in charge of each respective patient. Viremia was present in 79% of the patients (146 out of 184). The prevalence of HCV-genotypes differed significantly between Belgian and Saudi-Arabian dialysis-patients. In Belgian dialysis patients HCV-genotype 1b was most prevalent (i.e. 62%), while in Saudi-Arabian patients HCV-genotypes 4, 1b, and la were present in respectively 36,4%, 31,7%, and 25,8% of the HCV-PCR positive patients. Although there were significant differences between Belgian and Saudi-Arabian dialysis patients, no clinical data showed any significant correlation with the HCV-genotype. Transaminases, determined over a six months period, showed normal average values. Doubling of the transaminases, in at least one out of six measurements over a six monthly period, occurred only in 14% (alanine aminotransferase, ALT) and 10% (aspartate aminotransferase, AST) of the patients. In Belgian dialysis patients, HCV-genotype 4 (or HCV-genotype 5) significantly correlated with a more recent start of dialysis treatment. We conclude that there is a significant different geographical prevalence of HCV-genotypes in HCV-affected hemodialysis patients. None of the different HCV-genotypes shows any particular clinical expression. Transaminases are not a sensitive marker for ongoing HCV-replication in hemodialysis patients. In Belgian dialysis patients, a changing pattern of HCV-infection is suggested, with an increasing prevalence of HCV-genotype 4 (or HCV-genotype 5) in more recent years. These data suggest possible implications for the therapeutic strategy in dialysis patients.
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PMID:Prevalence and clinical expression of HCV-genotypes in haemodialysis-patients of two geographically remote countries: Belgium and Saudi-Arabia. 912 93

The intercellular adhesion molecule 1 (ICAM-1, CD54) and the lymphocyte associated antigen 3 (LFA-3, CD58) have been found in soluble form (sCD54 and sCD58) in human sera. Data concerning their role in chronic liver disease and their usefulness in disease monitoring are contradictory. We addressed the question whether elevated sCD54/sCD58 correlated either with disease activity or with decreased elimination secondary to reduced liver function in chronic hepatitis B. We studied 31 patients with chronic hepatitis B undergoing interferon alpha therapy in a longitudinal fashion. Serum concentrations of sCD54 and sCD58 were measured at four weeks interval by specific Sandwich ELISA during a follow-up period of ten months. The maximal difference in concentration of each biochemical parameter, e.g., delta AST, delta gGt, delta bilirubin, was determined for each patient during the whole follow-up period. These differences were correlated with the variation in sCD54 (delta sCD54) and sCD58 (delta sCD58) at the respective time points. Using this method, we were able to eliminate interindividual differences in serum concentrations for sCD54 and sCD58 and to avoid bias due to preselection of patients. We found that delta sCD54 correlated with delta AST (p = 0.001) and delta ALT (p = 0.002), whereas there was no such correlation for delta sCD58. Interferon therapy did not affect sCD54 or sCD58 levels. Neither hepatitis B viremia nor the immune response to hepatitis B during the time of seroconversion to anti-HBe did significantly increase sCD54 or sCD58 levels. However, delta sCD54 was associated with delta gamma GT (p = 0.005) and delta sCD58 correlated with delta bilirubin (p = 0.037); a negative correlation was found for delta sCD54 with delta cholinesterase (p = 0.007). Our findings imply that sCD54 and sCD58 may be associated with a decrease in liver function that accompanies hepatic disease activity. sCD54 and sCD58 did not prove useful to monitor disease activity or response to interferon therapy in chronic hepatitis B. From our data we conclude, that decreased elimination of soluble adhesion molecules sCD54 and sCD58 in advanced liver disease may be responsible for increased serum concentrations detected.
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PMID:Circulating ICAM-1 (sCD54) and LFA-3 (sCD58) in chronic hepatitis B--a longitudinal study in patients treated with interferon-alpha. 923 90


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