Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune chronic active hepatitis (CAH-A) is a chronic liver disease of unknown etiology that is believed to have an autoimmune pathogenesis. The disease is slowly progressive until hepatic failure and portal hypertension develop and either death or liver transplantation occur. Currently, the only widely recognized therapy is the administration of glucocorticoids, which have both anti-inflammatory and immunosuppressive actions. Many patients cannot tolerate such therapy because of the psychiatric, osteoporotic, and weight-enhancing actions of steroids. Tacrolimus (FK 506) is a new macrolide antibiotic that has an immunosuppressive activity that is estimated to be 10-200 times greater than that of cyclosporine. Because of its greater immunosuppressive activity, we have used it in the treatment of 21 patients with autoimmune chronic active hepatitis. Before each subject was treated, a liver biopsy and a panel of hematological, serological, and biochemical parameters were assessed. The Tacrolimus was administered orally at 12-h intervals, and the dose was controlled by monitoring plasma FK trough levels. After 3 months of therapy at an oral dose of 3 mg twice a day, having achieved a median blood level of 0.5 ng/ml, the serum ALT level was reduced by 80%, and the AST level was reduced by 70%. Modest change in the white blood cell count and platelet count were noted. The median BUN level increased from a level of 12 to 18 mg/dl, and the serum creatinine increased from 0.9 to 1.3 mg/dl. These preliminary data demonstrate that: 1) Tacrolimus can be used to successfully treat CAH-A; 2) the response of CAH-A to Tacrolimus treatment is rapid and sustained; and 3) a minor increase in the serum BUN and creatinine levels occurs as a consequence of Tacrolimus treatment. It is anticipated that with continued treatment for periods of 1-2 yr, the natural history of CAH-A will be changed such that hepatic failure and the requirement for liver transplantation may be averted.
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PMID:Tacrolimus: a potential new treatment for autoimmune chronic active hepatitis: results of an open-label preliminary trial. 753 44

Our aim was to verify whether the presence of antibodies to HCV envelope protein might mark the occurrence of liver damage, as recently suggested in the literature. Sera from 104 patients (62 male, 42 female) were tested: 84 were positive and 20 were negative to a second generation enzyme immunoassay for anti-HCV antibodies; 51 patients had mild chronic liver disease (44 chronic hepatitis, seven steatosis), 43 had liver cirrhosis (superimposed by hepatocellular carcinoma in 18) and ten were asymptomatic anti-HCV positive subjects with normal liver function tests. Besides, all sera were tested by means of an enzyme immunoassay for the presence of serum antibodies to the synthetic peptide S24A (SIYPGHVSGH RMAWDMMMNW SPTA) derived from amino acids 307-330 of HCV polyprotein. Anti-S24A antibodies were detected in 40/84 sera positive and 1/20 negative at anti-HCV testing (Pearson chi 2 12.29; p = 0.005). Among anti-HCV positive sera, no significant difference existed in anti-S24A status with regard to clinical evidence of liver disease, ALT concentration or HCV RNA positivity. Thus, anti-S24A antibodies are detectable in approximately half of HCV-positive sera, but they do not seem to add significant clinical information to existing tests or to be useful as putative markers of viraemia.
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PMID:Anti-envelope antibodies in anti-hepatitis C virus (HCV) positive patients with and without liver disease. 753 99

This study was designed to evaluate serum HCV-RNA, liver histology, and RIBA-II pattern in asymptomatic anti-HCV positive subjects with persistently normal or slightly (i.e. < or = 1.5 times the upper limit of the normal range) elevated serum ALT levels. To this purpose, 22 asymptomatic anti-HCV positive subjects (11 men and 11 women, median age 40, range 21-70 years) underwent liver biopsy and determination of serum HCV-RNA. Positivity for anti-HCV was determined by ELISA-2 and by RIBA-II. Serum HCV-RNA was determined by PCR. Our data show that: 1) 9/22 symptom-free, anti-HCV positive subjects had histological features of chronic liver disease associated with ongoing HCV infection; 2) four subjects had no histological signs of chronic hepatitis and normal serum ALT levels despite positivity for serum HCV-RNA; 3) serum ALT levels did not discriminate HCV-RNA positive subjects with from those without chronic hepatitis; 4) in anti-HCV positive subjects with normal serum ALT levels, a positive RIBA-II pattern was not always predictive of HCV viraemia or chronic hepatitis while an indeterminate RIBA-II pattern was frequently associated with nonspecific liver changes or normal histology. In conclusion, based on these findings, "true" healthy carriers of HCV (i.e. subjects with normal serum ALT levels and no histological features of chronic hepatitis despite HCV viraemia) may exist.
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PMID:Hepatitis C virus RNA in serum and liver histology in asymptomatic anti-HCV positive subjects. 753

To study the virological and serological characteristics of asymptomatic hepatitis C virus (HCV) carriers, 165 blood donors positive for antibody against HCV proteins by the second generation assay, were analyzed for their clinical backgrounds, serological reactivity against antigens derived from HCV by recombinant immunoblot assay, and the amount and genotype of HCV by the polymerase chain reaction. Compared with blood donors having abnormal levels of alanine aminotransferase (ALT), sera from the donors with normal levels of ALT reacted less frequently against NS4 antigens (anti-5-1-1: 34.4% vs. 54.5%, P = 0.0609; anti-c100-3: 34.4% vs. 56.1%, P < 0.05). Also the positivity for antibodies against these antigens were more frequent in sera from donors with genotype 1b HCV-RNA than other genotypes (anti-5-1-1: 61.0% vs. 23.5%, P < 0.01; anti-c 100-3: 61.0% vs. 26.5%, P < 0.01). The prevalence of each genotype in blood donors with normal ALT levels was different from that in patients with advanced liver disease (P < 0.05), genotype 1b being less and genotype 2a being more frequent. The number of HCV-RNA copies/0.5 ml in donors with normal ALT was 10(7.9 +/- 1.0) (n = 27) and that in patients with chronic liver disease was 10(7.4 +/- 0.8) (n = 116), the difference being statistically significant (P < 0.05). In conclusion, the results of this study suggest that asymptomatic blood donors carrying HCV have the serological and virological characteristics different from the patients with advanced liver disease.
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PMID:Virological and serological characterization of asymptomatic blood donors positive for anti-hepatitis C virus antibody. 754 61

The presence and significance of hepatitis C virus infection was evaluated in 241 renal transplant recipients from our hospital. Hepatitis C virus antibodies were tested by second-generation enzyme immunoassay, followed by second- and third-generation immunoblot assays (RIBA-2 and RIBA-3); hepatitis C virus RNA was measured by nested polymerase chain reaction. Hepatitis C virus antibodies, which were detected in 46.5% of patients, were mainly present before transplantation and independently associated with the total amount of transfused blood, time in hemodialysis and duration of posttransplant follow up. Liver dysfunction (alanine aminotransferase elevation) was observed in 50% of antibody-positive recipients, and 92.5% of patients with chronic liver disease without hepatitis B infection were infected with hepatitis C virus. Most antibody-positive patients (78.4%) tested positive by RIBA-2, but 21.6% were indeterminate; RIBA-3 was positive in 90% of these indeterminates. Hepatitis C virus RNA detection was positive in 96% of antibody-positive cases tested, in 20% of patients who were already anti-HCV negative before transplantation and also demonstrated persistence of HCV infection in all cases who, being antibody positive prior to transplantation, lost these antibodies during follow up (9% of transplanted patients). In conclusion, hepatitis C virus infection is extremely prevalent in renal transplant recipients from Spain and is the main cause of chronic liver disease in these patients. Confirmation by supplemental assays of anti-HCV antibodies is not necessary, but hepatitis C virus RNA testing is indispensable to detect those cases who lose or do not develop hepatitis C virus antibodies.
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PMID:Hepatitis C virus infection in renal transplant recipients: epidemiology, clinical impact, serological confirmation and viral replication. 760 77

To study the distribution of hepatitis C virus (HCV) in liver tissue and its pathogenesis, nonisotopic in situ hybridization with a digoxin labelled cDNA probe to 5'-NC region of HCV and immunohistochemical study with monoclonal anti-body of anti HCV C33c were performed on the liver tissue from 24 HCV infection patients with chronic liver disease. The results were as follows: In the liver tissue of 17 patients with HCV infection (both ELISA anti-HCV and nested PCR HCV RNA positive in serum), the positivity of HCV RNA and C33c were 82.3% (14/17) and 88.2% (15/17) respectively. In 7 patients with anti-HCV positive only HCV RNA was not detected in the liver tissue, but 4 out of these 7 cases were C33c positive. The specific signals of HCV RNA and C33c were mainly localized in the cytoplasm of hepatocytes. The distribution of the HCV infected hepatocytes was spotty, scattered or diffuse. There was no relationship between the distribution and the level of alanine transaminase or pathologic changes in liver. There were many lymphocytes and monoclear cells infitrating the periphery of HCV-infected liver cells. The results suggested that replication of HCV in the cytoplasm of hepatocytes elicits the host immune response in cells infected with HCV and this is important in the pathogenesis of HCV infection.
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PMID:[Detection of hepatitis C virus RNA and C33c antigen in the liver tissue from hepatitis C virus infection patients with chronic liver disease]. 764 39

The relationship between plasma hepatitis C virus (HCV) RNA levels, antibody positivity, and hepatocellular damage were studied in 41 patients with non-A, non-B chronic liver disease. The patients were placed into two groups according to the plasma levels of HCV-RNA: plasma HCV-RNA level was estimated as high when detected by a one stage polymerase chain reaction (PCR) and as low when detectable only after a two stage PCR. Anti-HCV (first and second generation assays) and anti-GOR were also measured. The mean alanine aminotransferase (ALT) level of the high HCV-RNA group was 115 +/- 62 IU/l, whereas that of the low HCV-RNA group was 59 +/- 37 IU/l (P < 0.05). Patients with ALT levels above 100 IU/l had invariably a high level of HCV-RNA. There were no differences in clinical features in relation to the presence of anti-GOR or anti-HCV. Circulating HCV-RNA levels but not anti-HCV or anti-GOR antibodies correlated with hepatocellular damage.
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PMID:Correlation of plasma hepatitis C virus RNA levels with serum alanine aminotransferase in non-A, non-B chronic liver disease. 768 56

Antibody against the recombinant protein Y19 deriving from non-structural region 3 (NS3) of the hepatitis C virus (HCV) genome was measured in the serum from 300 patients with nonA-nonB chronic liver disease including serial serum samples from these patients by using an enzyme linked immuno-sorbent assay. Simultaneously, antibodies to a synthetic core peptide (AR142) and the recombinant peptide of NS 3-4 region (C-100) were tested. Anti-Y19 antibody was detected in 83.3%, 65.2% and 76.6% of patients with nonA-nonB chronic hepatitis (n = 144), liver cirrhosis (n = 46) and hepatocellular carcinoma (n = 43), respectively. In sera of other chronic liver disease, the detection rate of anti-Y19 antibody was significantly low comparing to nonA-nonB chronic liver disease. Positive rates of the patients for AR142 antibody and C-100 antibody were similar to the one for Y19 antibody. Patients positive for Y19 antibody have a tendency to be positive for C-100 antibody. Serum Y19 antibody level during and after treatment with natural interferon alpha (IFN-alpha; 5MU, 24 weeks) was studied in 33 patients with chronic hepatitis C. The effectiveness of IFN therapy did not correlate with the Y19 antibody level before the treatment. In most cases Y19 antibody level decreased relating to the improvement of the serum ALT level during the treatment. Y19 antibody level declined not only during IFN treatment but after the treatment in Responder group (as assessed by normal ALT for 6 months after the treatment; n = 14). Whereas, in Non-responder group (the rest of Responder group; n = 16) Y19 antibody level was maintained to the level at the end of the treatment or elevated again to the level before the treatment. In Responder group, 6 of 7 cases in whose serum HCV-RNA disappeared at 6 months after the treatment, had decrease of Y19 antibody to less than 20% of the pretreatment level and Y19 antibody became undetectable in 4 cases at 6 months after the treatment. One case in whom Y19 antibody did not decrease by the treatment had an increase of serum ALT level and a relapse of the disease at 12 months after the treatment. 5 of 6 cases in "Responder" group that HCV-RNA remained positive had more than 20% of Y19 antibody level of the pretreatment level at 6 months after the treatment. Therefore the decrease of Y19 antibody level was closely related to the efficacy in terms of serum ALT level and HCV-RNA level.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Clinical significance of antibody to Y19 protein in nonA and nonB chronic liver disease]. 768 28

A total of 203 paediatric cancer treatment survivors were tested for serum antibodies against hepatitis-C virus (anti-HCV). Anti-HCV was detected in 41 patients (20.2%) with first generation anti-HCV ELISA. Positive results were confirmed in all samples retested with a second generation ELISA (n = 35) and in all but two cases re-analysed by immunoblotting (n = 23). Anti-HCV positive children had received significantly more blood product transfusions compared to seronegative patients. In 75 children (32%) chronic liver disease was found. It was defined as an elevation of serum alanine aminotransferase values to a least 2.5 times the upper limit of normal persisting for 6 months or longer. Hepatitis A was never detected, and in 58 children the chronic hepatopathy was unexplained by hepatitis B (non-A non-B chronic liver disease). Of these patients 29 (50%) were seropositive for anti-HCV. Surprisingly, non-A/non-B chronic liver disease was associated with anti-HCV in 14 of 19 solid tumour patients (78.9%), but in no more than 14 of 39 leukaemia and lymphoma patients (35.9%). This phenomenon was not explained by different rates of cytomegalovirus disease and drug toxicity related hepatopathies between the two groups. It may be related to differences of leukaemia/lymphoma compared to solid tumour therapy schedules (differential immunosuppression and liver toxicity).
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PMID:Association of hepatitis C virus infection with chronic liver disease in paediatric cancer patients. 768 44

Hepatitis C virus (HCV) is a major cause of transfusion-induced chronic liver disease in hemophiliacs, with 70% to 90% being anti-HCV positive. Seroreversion or loss of antibody response to HCV has been observed in a small proportion of human immunodeficiency virus-positive [HIV(+)] anti-HCV(+) hemophilic men. Despite the seroreversion to an anti-HCV-negative state, such patients continue to show serum alanine aminotransferase (ALT) elevations and biopsy evidence of cirrhosis and/or chronic active hepatitis. To determine the cause for the loss of anti-HCV antibody, we compared first- and second-generation anti-HCV enzyme immunosorbent assay (EIA 1.0 and 2.0), second-generation recombinant immunoblot (RIBA 2.0), and HCV-RNA amplification using polymerase chain reaction (PCR) in 19 "seroreverters" before and after seroreversion. There was no difference between 19 seroreverters and 59 persistently anti-HCV-positive hemophiliacs in mean ALT (1.1 +/- 0.1 XUL v 2.0 +/- 0.2 XUL; chi 2 = 1.80, P > .05), in mean CD4 (188 +/- 36/microL v 232 +/- 28/microL; t = 0.965, P > .05), or in the rate of progression to acquired immunodeficiency syndrome (13 of 19 [68.4%] v 30 of 59 [50.9%]; chi 2 = .987, P > .05, respectively). Before seroreversion, all 19 seroreverters (100%) were positive for EIA 1.0 and 2.0 and PCR, and all but 2 of 19 (89.5%) were RIBA 2.0 positive, whereas, after seroreversion, none were positive for EIA 1.0, 15 of 19 (78.9%) were positive for EIA 2.0, 8 of 18 (44.4%) were positive for RIBA 2.0, and 18 of 19 (94.7%) were positive for PCR. There was a lower CD4 lymphocyte number after seroreversion in those who were RIBA 2.0 negative as compared with those who were RIBA 2.0 positive (32 +/- 10/microL v 171 +/- 52/microL; t = 2.638, P > .05). These results indicate that HIV(+) anti-HCV(+) hemophilic men who undergo "HCV seroreversion" are truly infectious and anti-HCV positive by second-generation tests. Anti-HCV detection in immunosuppressed hosts is significantly improved by second-generation EIA and RIBA assays.
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PMID:The presence of hepatitis C virus (HCV) antibody in human immunodeficiency virus-positive hemophilic men undergoing HCV "seroreversion". 768 87


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