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

Primary biliary cirrhosis (PBC) is a rare chronic cholestatic disorder of unknown origin that can now be treated effectively with ursodeoxycholic acid (UDCA). The clinical course of PBC is very variable, but a significant proportion of patients eventually die or undergo liver transplantation. In this single-center prospective long-term study, we analyzed the effect of UDCA therapy (10 mg/kg b.w./day) on conventional liver function tests and we also investigated whether serial quantitative liver function tests are useful in the clinical management of patients with PBC. Fifteen patients, most of them in an early disease stage, were followed up for either 4 (n = 7) or 5 (n = 8) years. In addition to regular conventional liver function tests, every 12 months quantitative liver function tests were performed. Thus we measured galactose elimination capacity, indocyanine green half-life and lidocaine half-life. Quantitative liver function tests were also performed once in healthy volunteers. Treatment with UDCA significantly improved conventional liver function tests, and this effect was maintained for several years (values in U/l before therapy and 4 years after therapy: AP = 1,346 +/- 317 vs. 516 +/- 93; gammaGT 378 +/- 80 vs. 144 +/- 30; LAP 122 +/- 10 vs. 71 +/- 9; AST 61 +/- 19 vs. 34 +/- 12; ALT 90 +/- 19 vs. 68 +/- 35; GLDH 14.3 +/- 1.9 vs. 8.2 +/- 1.9). Quantitative liver function tests were not significantly different between healthy volunteers and patients (GEC 6.8 +/- 0.3 vs. 7.0 +/- 0.3 mg/kg x min; ICG half-life 4.2 +/- 0.4 vs. 3.7 +/- 0.3 min; lidocaine half-life 75 +/- 8 vs. 79 +/- 6 min). In the patients, results of quantitative liver function tests (GEC, ICG and lidocaine half-lives) were not affected by UDCA therapy and remained constant over time. In the 1 patient who was transplanted, serial quantitative liver function tests did not indicate deteriorating liver function earlier than the patient's progressive symptoms or conventional liver function tests. Thus UDCA therapy markedly improved conventional liver function tests in patients with PBC, and this effect was maintained for at least 4-5 years. Possibly due to the fact that most of the patients were in an early disease stage, serial quantitative liver function tests provided little additional information that was relevant for planning therapy in the individual patient.
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PMID:Serial quantitative liver function tests in patients with primary biliary cirrhosis: a prospective long-term study. 932 69

To study the early stages of cell death in various types of chronic liver injury, liver biopsies from a total of 26 patients, including 7 with chronic hepatitis C(CHC), 4 with chronic hepatitis B(CHB), 7 with alcoholic liver disease (ALD), 4 with autoimmune or drug hepatitis (AI/DH), and 4 with primary biliary cirrhosis(PBC), were examined by an in situ nucleotidyl transferase assay (ISNTA), which detects DNA fragmentation. Positive nuclei in hepatocytes and sinusoidal lining cells were counted in all parenchymal areas, excluding triads and areas of fibrosis, using a computer with Sigmascan software. The number of positive hepatocytes/mm2 was similar in the biopsies of patients with CHC, CHB, ALD and AI/DH, but significantly lower in PBC. The number of positive sinusoidal lining cells/mm2 was significantly greater in biopsies with CHC compared to CHB, ALD, AI/DH and PBC. Double staining revealed that the ISNTA-positive sinusoidal lining cells were also CD68 positive, indicating that they were Kupffer cells. The frequency of ISNTA positivity did not correlate with serum AST or ALT levels, steatosis, cell swelling or cirrhosis. ISNTA-positive hepatocytes were more frequent than acidophilic bodies in every disease category. We conclude that apoptosis may be a common pathway of cell death in different liver diseases, that the high frequency of DNA fragmentation in Kupffer cells in CHC suggests that during chronic hepatitis C infection activated Kupffer cells may be subject to regulatory control by apoptosis and that ISNTA is more sensitive than acidophilic bodies in assessing the degree of cell injury in the liver.
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PMID:Frequency and distribution of DNA fragmentation as a marker of cell death in chronic liver diseases. 933 40

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

Heptral (S-adenosine-L-methionine) was given to 32 patients with chronic diffuse diseases of the liver and intrahepatic cholestasis. 16 of them had primary biliary cirrhosis (PBC). Phase I of the treatment lasted 16 days when the drug was injected intravenously in a dose 800 mg/day. It was followed by phase 2--1600 mg/day taken for 16 days. A response was registered in the majority of patients. They had relieved symptoms of asthenia, skin pruritus, jaundice. The patients with liver cirrhosis and chronic hepatitis exhibited a statistically significant fall in ALT, AST and GGTP. PBS patients showed insignificant lowering of cholesterol, bilirubin. No resistance was noted in repeated courses. Heptral tolerance was satisfactory.
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PMID:[Clinical trial of heptral in patients with chronic diffuse liver disease with intrahepatic cholestasis syndrome]. 986 18

Autoimmune cholangitis is an idiopathic disorder with mixed hepatocellular and cholestatic findings. Our goal was to characterize the disease prospectively by application of uniform diagnostic criteria. Twenty patients were identified and compared with 242 patients with conventional forms of autoimmune liver disease. Patients with autoimmune cholangitis were distinguished from type 1 autoimmune hepatitis (AIH) by lower serum levels of aspartate transaminase (AST), gamma-globulin, and immunoglobulin G; higher serum levels of alkaline phosphatase; and lower frequencies of autoantibodies. They were distinguished from primary biliary cirrhosis (PBC) by higher serum levels of AST and bilirubin, lower serum concentrations of immunoglobulin M, and greater occurrence of autoantibodies. Their female predominance, lower serum alkaline phosphatase levels, higher frequency of autoantibodies, and absence of inflammatory bowel disease differentiated them from primary sclerosing cholangitis (PSC). Laboratory findings ranged widely and did not characterize individual patients. HLA risk factors were similar to those of type 1 AIH and PBC, and different from those of PSC. Treatment responses to corticosteroids or ursodeoxycholic acid were poor. Composite histological patterns resembled mainly PBC or PSC. We conclude that autoimmune cholangitis diagnosed by prospective analysis cannot be assimilated into a single, conventional, diagnostic category. It may represent variant forms of diverse conditions, a transition stage, or a separate entity with varying manifestations.
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PMID:Autoimmune cholangitis within the spectrum of autoimmune liver disease. 1207 15

Ursodeoxycholic acid (UDCA) is a safe and effective medical therapy for most patients with primary biliary cirrhosis (PBC), but some patients show an incomplete response. Silymarin is a potent antioxidant with immunomodulatory and antifibrotic properties. The aim of this study was to evaluate the safety and assess the efficacy of silymarin in patients with PBC who had shown a suboptimal response to UDCA. Twenty-seven patients with PBC who had been on UDCA (13-15 mg/kg/day) therapy for 7 to 221 months and had shown a persistent elevation of alkaline phosphatase activity at least 2 times the upper limit of normal for more than 6 months were enrolled. Oral silymarin, 140 mg 3 times daily was given for 1 year, and patients continued on the same dosage of UDCA. No significant changes in serum alkaline phosphatase activity (897 +/- 84 vs. 876 +/- 95, P =.5), total bilirubin (0.9 +/- 0.1 vs. 1 +/- 0.1, P =.07), aspartate transaminase (AST) (58 +/- 5 vs. 56 +/- 6, P =.4), albumin (4.0 +/-.06 vs. 4.1 +/-.06, P =.4), or Mayo risk score (3.82 +/- 0.2 vs. 3.88 +/- 0.2, P =.4) were noted after 1 year of treatment with combination therapy. Transitory gastrointestinal adverse events occurred in 2 patients. In conclusion, although silymarin was well tolerated, this medication did not provide benefit to patients with PBC responding suboptimally to UDCA. The results of this pilot study would seem to discourage further controlled trials of silymarin in patients with PBC.
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PMID:Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid. 1117 60

Background/Aim: Hepatic venography with a positive-contrast medium has been reported as a method for evaluating liver disease. However, the contrast medium used in this method provides insufficient portal vein observation and may cause severe liver injuries. Carbon dioxide (CO(2)), a negative-contrast medium, may be able to depict the portal vein system with minimal hepatic toxicity. The aim of this study was to evaluate the usefulness and side-effects of balloon-occluded hepatic venography with CO(2) (CO(2) venography) and to evaluate the correlation between retrograde portogram and liver function in patients with cirrhosis. Subjects and methods: The subjects consisted of 23 biopsy-proven cirrhotic patients (male:female, 16:7; age, 58+/-12 years, range 34-80). The causes of cirrhosis were alcohol intake in ten, HCV infection in ten, HBV infection in one, primary biliary cirrhosis in one and Budd-Chiari syndrome in one. Of these patients, six were complicated with hepatocellular carcinoma (HCC). CO(2) venography was performed with an occlusion balloon catheter, and 25 ml of CO(2) was infused. CO(2) portograms were scored as follows: 0, no visualization of portal veins; 1, visualization of peripheral portal branches; 2, unilateral first portal branch; 3, bilateral first portal branches; 4, main portal vein; 5, left gastric vein, superior mesenteric vein and splenic vein. Hepatic venous pressure gradient (HVPG), cardiac functions, biochemical analysis, blood gas analysis and oxygen (O(2)) saturation monitoring were measured simultaneously. Arterio-portography was also performed. To evaluate the usefulness of CO(2) venography in patients with HCC accompanied by portal vein tumor thrombus (PVTT), three patients were also examined. Results: No significant changes in ALT, AST, O(2) saturation or blood gas data were observed after CO(2) venography. A statistically significant positive correlation was observed between CO(2) portogram scores and Child-Pugh scores (r=0.68, P=0.003). The correlations between CO(2) portogram scores and HVPG, and the forms of gastroesophageal varices in patients without PVTT and major shunts were not significant. The CO(2) portogram score was significantly higher in patients with alcoholic liver cirrhosis than in those with HCV-positive cirrhosis (P=0.04). Cavernous transformation and peripheral portal branches were demonstrated in patients with HCC accompanied by PVTT. These findings could not be observed by arterio-portography. Conclusion: CO(2) venography to obtain retrograde portogram is a safe and useful method for evaluating the portal vein system and liver function in patients with liver cirrhosis.
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PMID:Evaluation of balloon-occluded hepatic venography with carbon dioxide for portography and correlation between retrograde portogram and liver function in patients with liver cirrhosis. 1105 28

To clarify the role of IP-10 in autoimmune liver diseases, we studied the serum levels of IP-10 in 14 patients with autoimmune hepatitis (AIH), 23 patients with primary biliary cirrhosis (PBC), and 65 patients with chronic viral hepatitis (20 type B and 45 type C). The hepatic expression of IP-10 mRNA and the correlation between the serum levels of IP-10 and clinical parameters were also evaluated. In addition to 20 healthy controls, 16 rheumatoid arthritis (RA) patients were included as an extrahepatic inflammatory disease. The serum level of IP-10 was significantly (P < 0.02) higher in patients with AIH, PBC, and chronic hepatitis B and C than in healthy controls, and it was significantly correlated (P < 0.05) with the serum levels of aspartate aminotransferase and alanine aminotransferase in patients with AIH, PBC, and chronic hepatitis B and C. The serum level of IP-10 was not elevated in RA patients. After successful treatment of AIH and chronic hepatitis C, the serum level of IP-10 decreased to the same level as in healthy volunteers. As we previously showed in cases with chronic hepatitis B or C, in situ hybridization in both AIH and PBC cases demonstrated the expression of IP-10 mRNA in hepatocytes around focal or lobular necrosis surrounded by infiltrating mononuclear cells, whereas IP-10 mRNA was not expressed in areas around the damaged bile ducts in PBC cases. The present results suggest that IP-10 is specifically produced by hepatocytes in inflammatory areas irrespective of the aetiology of hepatitis, and that IP-10 may help to recruit T cells to the hepatic lesions in autoimmune liver diseases as well as in chronic viral hepatitis.
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PMID:Increase of chemokine interferon-inducible protein-10 (IP-10) in the serum of patients with autoimmune liver diseases and increase of its mRNA expression in hepatocytes. 1120 58

Significant amounts of ursodeoxycholic acid (UDCA) used for the treatment of patients with primary biliary cirrhosis (PBC) become epimerized at C-3 to isoUDCA. We investigated the metabolism of isoUDCA and a possible pharmacologic effect in five patients (51.4 +/- 5.8 years old; 3 females, 2 males) with PBC and persistent elevations of gamma-glutamyl transpeptidase (gamma-GT) and alkaline phosphatase despite treatment with UDCA for more than one year. Serum samples were analyzed for bile acid metabolites and surrogate markers of cholestasis in 4-week intervals after 1 g/d UDCA, wash-out, 0.5 g/d isoUDCA, 0.75 g/d isoUDCA, 0.75 g/d UDCA, and two further periods with 1 g/d UDCA. Bile acids in urine were analyzed after wash-out, 0.5 and 0.75 g/d isoUDCA, and 0.75 and 1 g/d UDCA. During wash-out, AST, AP, and gamma-GT rose significantly (P < 0.05) but reversed to previous levels during the first isoUDCA period, with 0.5 g/d only. No further improvements were observed after increasing the dose of isoUDCA or switching back to UDCA. In serum, the relative amounts of isoUDCA and UDCA were 8.1 +/- 7.4% and 16.2 +/- 6.4% during 0.5 g/d isoUDCA, 6.2 +/- 2.5% and 45.0 +/- 4.1% during 0.75 g/d isoUDCA, and 0.5;-3% and 56.4;-60.0%, respectively, during UDCA. In urine, UDCA was the predominant bile acid both during isoUDCA and UDCA medications. The similar serum enrichment and urinary excretion of UDCA during administration of either isoUDCA or UDCA together with low concentrations of the intermediate of isomerization, 3-dehydro-UDCA, indicate a first-pass epimerization of isoUDCA to UDCA in the liver. Approximately 25% of serum isoUDCA and 10% of serum UDCA were conjugated with either glucuronic acid or N-acetylglucosamine, indicating hepatic formation and systemic secretion of glycosidic conjugates. In PBC patients, isoUDCA becomes isomerized to UDCA and has similar effects on surrogate markers of cholestasis. Thus, isoUDCA has pro-drug characteristics.
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PMID:Isoursodeoxycholic acid: metabolism and therapeutic effects in primary biliary cirrhosis. 1135 80


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