Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 51-year-old woman who had been treated for primary biliary cirrhosis (PBC) was admitted to our hospital for evaluation of unexplained, isolated, persistently increased aspartate aminotransferase (AST) activity. Results of laboratory tests on admission showed: AST 171 KU, alanine aminotransferase 28 KU, and anti-mitochondrial titer 1/1280. Results of hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (HCV Ab; C100-3) assays were negative. Histology of a liver biopsy specimen was compatible with a diagnosis of PBC (stage III of Scheuer's classification). The molecular size of serum AST was estimated to be more than 500,000 by high-performance size-exclusion liquid chromatography. Electrophoretic analysis showed an abnormal band of AST between supernatant AST (sAST) and mitochondrial AST (mAST), which band was characteristic of AST-immunoglobulin complexes (AST-Ig). Ouchterlony double-diffusion and immunoprecipitation tests identified the immunoglobulin component as IgM. The presence of AST-Ig appeared to be responsible for the elevated serum AST.
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PMID:Aspartate aminotransferase-linked immunoglobulin complexes in serum of a patient with primary biliary cirrhosis. 801 13

Relationships between liver biochemical test values and reported frequency of consumption of various foods were examined using a principal-component analysis of data from 42 patients with chronic liver disease. The statistical procedure identified relationships among biochemical and dietary variables. One relationship included the variables albumin, bilirubin, and frequency of intake of fruits and vegetables, starch, and meats. A relationship was also found between serum alkaline phosphatase (ALP) levels and fat/oil intake. Data from patients with primary biliary cirrhosis (PBC) and noncholestatic liver disease were compared using a correlational analysis. In patients with PBC, serum ALP levels were positively correlated with frequency of intake of fat/oil (r = 0.59, p < 0.01) and meats (r = 0.46, p < 0.05), whereas serum bilirubin (Bili) and aspartate aminotransferase (AST) levels were significantly correlated with frequency of intake of dairy products (rs = 0.48 and 0.45, ps < 0.05 for Bili and AST, respectively), meats (rs = 0.59 and 0.65, ps < 0.01), and fat/oil (r = 0.54, p < 0.02 and r = 0.48, p < 0.05). In patients with noncholestatic liver disease, Bili levels were correlated with frequency of intake of fat/oil (r = 0.58, p < 0.01), and fruits and vegetables (r = 0.68, p < 0.01). These results suggest that the degree of elevation of some liver biochemical tests in patients with liver disease may be affected by dietary intake.
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PMID:Relationship between liver biochemical tests and dietary intake in patients with liver disease. 807 8

In order to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of Chinese patients with primary biliary cirrhosis, a short-term, randomized, double-blind controlled, cross-over study was done with long-term follow up. In the first part of the study, 12 patients were randomly chosen to receive either UDCA 600 mg/day for 3 months followed by a placebo for 3 months or a placebo for 3 months followed by UDCA for 3 months. The clinical symptoms of pruritus improved when the patients were receiving UDCA but became worse when receiving a placebo. Mean serum levels of alkaline phosphatase (ALPase), gamma-glutamyl transferase (gamma-GT), total bilirubin, cholesterol, alanine aminotransferase (ALT) and aspartate aminotransferase all decreased below the baseline values when receiving UDCA treatment and all increased above the baseline values when receiving the placebo. The difference was statistically significant. In the second part of the study, 19 patients received long-term UDCA treatment (mean 20 months). The clinical symptoms of pruritus improved in 90% of the pruritic patients. Serum levels of ALPase, gamma-GT and ALT fell significantly from the pretreatment values, 6, 12 and from the mean 20 months after UDCA treatment. Serum levels of total bilirubin fell significantly 6 and 12 months after UDCA treatment but did not reach statistical significance at the last follow up. No patient lost antimitochondrial antibody and elevated immunoglobulin levels did not improve significantly, but the Mayo clinical risk score improved significantly after long-term UDCA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a short-term, randomized, double-blind controlled, cross-over study with long-term follow up. 810 Jan 53

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 reports on a group of 20 patients with an initial diagnosis of primary biliary cirrhosis (PBC) whose serum tested negative for antimitochondrial antibodies by immunofluorescence. All had a clinical history compatible with primary biliary cirrhosis, and results of biochemical, histological, and radiological investigations were consistent with this diagnosis despite the absence of antimitochondrial antibodies by immunofluorescence. For comparison, these patients were matched for sex and serum bilirubin with 20 antimitochondrial antibody positive (> 1:160) and histologically confirmed primary biliary cirrhosis patients who served as controls. Serum samples from both groups were retested blindly for antimitochondrial antibodies using immunoblotting and for antibodies to the major M2 mitochondrial autoantigens by enzyme linked immunosorbent assay (ELISA). Three antimitochondrial antibody immunofluorescence negative patients had antimitochondrial antibodies by immunoblotting and ELISA; the remaining 17 patients were confirmed negative by all methods. The antimitochondrial antibody immunofluorescence positive controls were verified by immunoblotting or ELISA, or both. All 17 patients negative for antimitochondrial antibodies had antinuclear antibodies, often in high titres, compared with 3/17 of the antimitochondrial antibody positive controls (p = 0.0001). Additionally, the antimitochondrial antibody negative group also had significantly higher smooth muscle antibody titres (p = 0.03) and lower serum IgM (p = 0.01) and aspartate aminotransferase (p = 0.03) activities than the antimitochondrial antibody positive controls. Analysis of clinical findings, histological tests, serum bilirubin, alkaline phosphatase, alanine aminotransferase, and IgG, disclosed no significant differences between the two groups. This paper describes a group of patients with the clinical and histological features of PBC but who do not fulfil the usual criteria necessary to make this diagnosis. Because they also have very high titres of antinuclear antibodies, smooth muscle antibodies, and comparatively low IgM and aspartate aminotransferase activities, we believe they are distinct from PBC and have a syndrome of autoimmune cholangitis.
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PMID:Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis. 830 80

Immunological abnormalities frequently observed in patients with primary biliary cirrhosis are considered to be related to the pathogenesis of this disease. We performed a prospective trial to evaluate whether immune mechanisms play a role in the effectiveness of ursodeoxycholic acid (UDCA) therapy. Fifteen female patients with primary biliary cirrhosis were followed for 1 year and were then treated with UDCA (600 mg/day) for another year. Laboratory tests, including peripheral blood lymphocyte subsets assessed by dual colour fluorescence analysis using monoclonal antibodies against respective T cell markers, were evaluated at the beginning of the study, at the start of therapy and at the end of therapy. In primary biliary cirrhosis, the proportion of cytotoxic T cells, suppressor inducer T cells and alpha beta-receptor bearing T cells were significantly lower than in healthy controls. No significant changes were observed in the proportions during the year before the therapy. These reductions, however, recovered to normal ranges after 1 year of UDCA therapy. These changes were associated with an improvement in the serum levels of aspartate aminotransferase, alkaline phosphatase, gamma-globulin and IgM. The close correlation between the improvement in the imbalance of lymphocyte subsets after the therapy and the clinical status suggests that an immunological process may play a role in the effectiveness of therapy in primary biliary cirrhosis.
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PMID:Improvement of peripheral blood lymphocyte subsets in primary biliary cirrhosis after ursodeoxycholic acid therapy. 871 4

A randomized concentration-controlled clinical trial (RCCCT) is a trial design in which patients are randomized to predefined blood drug concentrations (low, medium, high). If the concentration ranges are sufficiently separated, this study design can reveal important blood concentration-response relations. Tacrolimus is a potent yet "infant" immunosuppressant for the treatment and prevention of graft rejection and has been shown to exhibit significant clinical activity in some immune-mediated disorders. A tacrolimus artificial intelligence modeling system (AIMS) was used to guide patient dosing to achieve target concentrations specified by the study protocols. In the Multiple Sclerosis study group, we were able to define a concentration range (0.3-0.7 ng/ml) that appeared to show efficacy and minimal tacrolimus toxicity. Patients randomized to the high zone (0.6-1.2 ng/ml) in the Primary Biliary Cirrhosis study group showed significant reduction (approximately 50%) in surrogate efficacy markers [aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT)] compared with patients in the low zone (0.1-0.6 ng/ml). Therefore the RCCCT allowed the detection and delineation of clinically significant concentration-response relations in an ethical and efficient manner.
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PMID:Computer-guided randomized concentration-controlled trials of tacrolimus in autoimmunity: multiple sclerosis and primary biliary cirrhosis. 885 64

Recent data suggest that plasma levels of the phase II detoxification enzyme glutathione S-transferase alpha may be a sensitive indicator of hepatocellular integrity in acute liver disorders but little information is available in chronic hepatic disorders. Using a newly developed enzyme linked immunosorbent assay, glutathione S-transferase A1-1 (GSTA1-1) levels were measured in 279 plasma samples from patients with chronic liver disorders. Results were categorized as normal or elevated plasma GSTA1-1 and normal or elevated plasma aspartate aminotransferase (AST) levels. In 24 patients with alcoholic liver cirrhosis, plasma GSTA1-1 levels were not significantly different from a group of 350 healthy controls and only one patient (4%) had an elevated GSTA1-1 level while 10 (42%) patients had elevated AST activities. In samples from patients with primary biliary cirrhosis (n = 150), primary sclerosing cholangitis (n = 26) or chronic hepatitis (n = 79) significantly (P < 0.0001) elevated plasma GSTA1-1 concentrations were detected in 25 (17%), 7 (27%) and 17 (22%) of the samples, respectively. AST activities were increased in a higher percentage of samples in all three disorders: 89%, 88%, and 57%, respectively. Plasma GSTA1-1 and AST levels were significantly correlated (P < 0.005) in the above mentioned disorders but not in alcoholic liver cirrhosis. It is concluded that plasma GSTA1-1 is not a sensitive parameter for the detection of hepatocellular damage in chronic liver disorders.
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PMID:Plasma glutathione S-transferase alpha 1-1 levels in patients with chronic liver disorders. 904 44

The serum concentrations of CA19-9 and carcinoembryonic antigen (CEA) were measured in 150 consecutive patients with histologically proven liver disease admitted to a liver unit for transplant assessment. A significant proportion of the cases studied had a CA19-9 above the upper limit of the reference range (35 kU/L): alcoholic liver disease (73%), primary sclerosing cholangitis (61%), primary biliary cirrhosis (60%), chronic hepatitis B (71%), chronic hepatitis C (84%), autoimmune hepatitis (36%) and hepatocellular carcinoma (54%). CEA was only elevated in a small proportion of the patients with benign liver disease and the degree of elevation was small (15-37 micrograms/L). Significantly raised CEA was observed in two patients (15%) with hepatocellular carcinoma. Statistically significant correlations were observed between the serum CA19-9 concentration and standard parameters of liver dysfunction: positive correlations with aspartate aminotransferase, alkaline phosphatase and bilirubin and negative correlations with albumin and gamma-glutamyltransferase. Positive relationships were also observed between CA19-9 and both CEA and creatinine. Both increased production of CA19-9 from biliary epithelial cells and decreased clearance due to cholestasis may be contributing to the elevation of CA19-9 in the bloodstream. Our data indicate that caution is needed in the interpretation of CA19-9 results in the presence of liver dysfunction.
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PMID:The effect of benign and malignant liver disease on the tumour markers CA19-9 and CEA. 946 46

Ursodeoxycholic acid (UDCA) has been shown to have beneficial effects on patients with primary biliary cirrhosis, suggesting that UDCA has immunomodulating effects. We investigated the effect of UDCA in patients with autoimmune hepatitis (AIH) which is characterized by immunological abnormalities. Eight patients with type 1 AIH were treated with 600 mg of UDCA per day for 2 years. Based on the criteria of the International Autoimmune Hepatitis Group, five patients were diagnosed as definite and three as probable type 1 AIH. Liver function tests were performed every 4 weeks, before and during UDCA therapy and the serum levels of anti-nuclear antibodies (ANA), smooth muscle antibodies (SMA), immunoglobulin G and gamma globulin were determined every 3 months. The levels of serum aspartate aminotransferase and alanine aminotransferase significantly decreased from 154 +/- 24 IU/L and 170 +/- 17 IU/L before UDCA therapy to 31 +/- 3 IU/L and 25 +/- 5 IU/L (P < 0.001) after 1 year of treatment and 28 +/- 2 IU/L and 23 +/- 4 IU/L (P < 0.001) after 2 years of treatment. After 2 years of treatment, the levels of serum immunoglobulin G and gamma globulin significantly decreased (P < 0.05) and ANA titres (5/8 patients) were reduced and SMA (3/5 patients) became negative. Furthermore, hepatic histopathological changes of four patients were assessed after 1 year of treatment, and an improvement of intrahepatic inflammation, but not fibrosis, was observed. In conclusion, these results suggest that UDCA has a beneficial therapeutic effect in patients with type 1 autoimmune hepatitis.
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PMID:Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis. 964 39


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