Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred and eighty nine patients with primary biliary cirrhosis were entered into a double blind, placebo controlled randomised trial starting in January 1978 to assess the therapeutic value of d-penicillamine 1200 mg daily. Eighteen of the 98 patients receiving d-penicillamine and 22 of the 91 placebo treated patients died during the study. Thirty six per cent of those on d-penicillamine and 8% of those on placebo were withdrawn from the study. No difference in overall survival was noted between the two groups of patients whether the results were analysed for the entire period of observation or only during the period in which the patients were receiving therapy. The mortality rate of those receiving d-penicillamine in histological stage I to II, however, was one third of that of the placebo group although this difference did not reach statistical significance. Using the occurrence rate ratio as the statistical method of analysis, no effect of d-penicillamine was noted on any clinical, biochemical or histological features examined, except the serum alanine aminotransferase activity which was greater in those on active treatment. In this trial we have been unable to establish any therapeutic benefit from the drug.
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PMID:Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis. 388 23

Biliary glycoprotein I (BGP I), a constituent of normal bile and serum, is a glycoprotein (mol. wt. approximately 90,000) containing about 40% carbohydrate. Serum BGP I (S-BGP I) was determined by means of a double-antibody radioimmunoassay in patients with liver and gastrointestinal disease and in healthy individuals. The serum levels of five liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (S-ALP), gamma-glutamyltranspeptidase (S-GT), and lactic dehydrogenase), bilirubin (total and conjugated), and bile acids (cholic and chenodeoxycholic acid) were determined in parallel. Healthy individuals had 0.5 +/- 0.3 mg/l of S-BGP I (mean +/- 2 S.D.; range, 0.2-0.9 mg/l). Most patients with liver disease (chronic hepatitis, alcoholic cirrhosis, primary biliary cirrhosis) had elevated levels, up to 5-10 times the upper reference limit, whereas most patients with gastrointestinal disease (ulcerative colitis, Crohn's disease, other GI diseases) had normal values. In patients with liver disease S-BGP I was positively correlated (p less than 0.0005) to S-GT. In primary biliary cirrhosis a positive correlation (p less than 0.005) between S-BGP I and S-ALP was also obtained. All other comparisons between S-BGP I and the other liver function tests showed non-significant correlations. It is concluded that S-BGP I is a determinant of cholestasis of similar use as S-GT.
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PMID:Serum level of biliary glycoprotein I, a determinant of cholestasis, of similar use as gamma-glutamyltranspeptidase. 611 67

To study autoantibodies against liver cell surface membrane clinically, anti-LP-1 and anti-Tamm-Horsfall glycoprotein (THGP) were determined in the sera of patients with various liver diseases. They were detected by ADCC assay using antigen-coated cells as the target. A high incidence of anti-LP-1 was seen in chronic hepatitis (CH), liver cirrhosis (LC), primary hepatic cancer with cirrhosis (PHC), and primary biliary cirrhosis. The incidence of anti-THGP was also high in CH, LC, and PHC. Both anti-LP-1 and anti-THGP were detected in 2 of 3 patients with lupoid hepatitis. The patients studied here had no obvious evidence of renal tubular acidosis or pyelonephritis. Serum alanine transaminase activity, serum gamma-globulin content, and the presence of rheumatoid factors were not associated significantly with the presence of anti-LP-1 or anti-THGP in chronic liver disease. In 7 cases of CH tested serially during their clinical course, anti-LP-1 and/or anti-THGP tended to appear during acute exacerbations. The demonstration of anti-LP-1 and anti-THGP suggested that their appearance was related to the development of chronic liver disease.
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PMID:Studies on anti-LP-1 and anti-Tamm-Horsfall glycoprotein in chronic liver disease using ADCC assay against antigen-coated target cells. 718 May 72

We determined the serum molybdenum concentration by neutron activation analysis in apparently healthy subjects and in patients with diseases of the liver and biliary system. The level was found to be markedly elevated in the initial phase of acute viral hepatitis (mean +/- S.D. 3.10 +/- 1.46 ng/ml vs. 0.55 +/- 0.21 in controls) and to return to normal during convalescence, in parallel with the liver function tests. The most significant correlations were found between the serum molybdenum concentration and the serum levels of GOT ( r = 0.710, p less than 0.001) and GPT (r = 0.683, p less than 0.001). Besides, the serum molybdenum level (mean +/- S.D.) was observed to be definitely increased in patients with HBsAg-positive chronic active hepatitis (0.97 +/- 0.49 ng/ml), HBsAg-positive liver cirrhosis (1.01 +/- 0.50), alcoholic liver disease (1.32 +/- 0.56), liver metastases (1.40 +/-0.39), gallstones (1.28 +/- 0.38), tumors of the gallbladder or extrahepatic bile ducts (1.64 +/- 0.44), and carcinoma of the head of the pancreas (1.61 +/- 0.91). Finally, the serum molybdenum level was found to be raised in two patients with primary biliary cirrhosis and in two out of four patients with drug-induced liver injury. The etiologic mechanism and the clinical importance of the observed abnormality remain to be established. Our study enlarges the existing information concerning the disorders of trace element metabolism in liver diseases.
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PMID:Serum molybdenum in diseases of the liver and biliary system. 720 61

The liver has an important role in thyroid hormone metabolism and the level of thyroid hormones is also important to normal hepatic function and bilirubin metabolism. Besides the associations between thyroid and liver diseases of an autoimmune nature, such as that between primary biliary cirrhosis and hypothyroidism, thyroid diseases are frequently associated with liver injuries or biochemical test abnormalities. For example, thyroid diseases may be associated with elevation of alanine aminotransferase and alkaline phosphatase, which is mainly of bone origin, in hyperthyroidism and aspartate aminotransferase in hypothyroidism. Liver diseases are also frequently associated with thyroid test abnormalities or dysfunctions, particularly elevation of thyroxine-binding globulin and thyroxine. Hepatitis C virus infection has been connected with thyroid abnormalities. In addition, antithyroid drug therapy may result in hepatitis, cholestasis or transient subclinical hepatotoxicity, whereas interferon (IFN) therapy in liver diseases may also induce thyroid dysfunctions. These thyroid-liver associations may cause diagnostic confusions. Neglect of these facts may result in over of under diagnosis of associated liver or thyroid diseases and thereby cause errors in patient care. It is suggested to measure free thyroxine (FT4) and thyroid-stimulating hormone (TSH) which are usually normal in euthyroid patients with liver disease, to rule out or rule in coexistent thyroid dysfunctions, and consider the possibility of thyroid dysfunctions in any patients with unexplained liver biochemical test abnormalities. It is also advisable to monitor patients with autoimmune liver disease or those receiving IFN therapy for the development of thyroid dysfunctions, and patients receiving antithyroid therapy for the development of hepatic injuries.
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PMID:Clinical associations between thyroid and liver diseases. 754 16

We evaluated the clinical significance of the antibody to hepatitis C core protein (anti-p22) analysing 147 sera from 99 patients; 45 of them had post-transfusion non A non B (NANB) hepatitis, 28 cryptogenic non A non B hepatitis, 12 chronic hepatitis B, 7 chronic hepatitis D, 6 other forms of liver disease (4 primary biliary cirrhosis, 2 autoimmune hepatitis) and 1 rheumatoid arthritis. All sera were tested by commercial 1st and 2nd-generation ELISAs and anti-p22 single antibody ELISA. We found a highly significant correspondence between anti-p22 and commercial assays (p = 0.0001). HCV-RNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in sera showing positive or negative concordant results and in all sera (24) that showed discordant results by anti-p22 and commercial ELISAs. HCV-RNA was found in 14 of 17 (82%) anti-p22 positive sera that were negative by commercial ELISAs, in 1 of 7 (14.3%) anti-p22 negative sera that were positive by commercial ELISAs (p = 0.001) and in all control sera from patients with positive concordant results. It was undetectable in 7 sera from patients with autoimmune diseases (negative by all ELISAs). We studied follow-up sera from 16 patients treated with interferon: 8 long-term responders (with persistently normal ALT levels for at least 24 months after discontinuation of therapy and histological remission) and 8 non-responders. Sera were also tested by a 4-antigen recombinant immunoblotting assay (RIBA II).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical significance of the antibody to the putative core protein of hepatitis C virus in patients with chronic liver disease. 769 Aug 74

Antimitochondrial antibodies are of considerable importance for the diagnosis of primary biliary cirrhosis. Several subtypes of antimitochondrial antibodies have been identified and the pattern has been associated with prognosis of the disease in the long term course. 22 patients with primary biliary cirrhosis (19 female, 3 male; age 29-66, mean 49 years) were examined for the occurrence of the subtypes of antimitochondrial antibodies anti M2, anti M4 and anti M9. Diagnosis of primary biliary cirrhosis was based on elevated cholestatic enzymes, antimitochondrial antibodies, histology and exclusion of other chronic liver disease in all patients and elevated serum IgM concentration in 18/22 patients. Most patients were included in a study protocol of the Swiss Association for the Study of the Liver and treated with 10 mg/kg/day oral ursodeoxycholic acid. According to the subtype pattern of antimitochondrial antibodies, patients were divided into 4 groups A to D (A: anti M2-, anti M4-, anti M9+; B: anti M2+, anti M4-, anti M9+; C: anti M2+, anti M4-, anti M9- and D: anti M2+, anti M4+, anti M9-). The groups were compared with respect to the prognostically relevant parameters age, bilirubin, albumin, prothrombin time and peripheral edema, as well as the occurrence of granulomas in liver biopsy, galactose elimination capacity and response to treatment with ursodeoxycholic acid during one year. Treatment response was expressed as decrease of the serum concentration of IgM, GPT, alkaline phosphatase, gamma glutamyl transpeptidase and bilirubin. No significant differences between the four groups were found with respect to the prognostically relevant parameters, histology and galactose elimination capacity at study entry.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Significance of subtype pattern of antimitochondrial antibodies in primary biliary cirrhosis for prognostic parameters and response to ursodeoxycholic acid]. 774 Feb 90

A 60-year-old woman with chronic active hepatitis C was treated with 6 million units of rIFN-alpha 2b daily for two weeks and subsequently three times weekly for several months. Histological examination proved a severe form of chronic active hepatitis C unexpectedly complicated with primary biliary cirrhosis (PBC). Before treatment, levels of serum alkaline phosphatase (ALP) or gammaglutamyltranspeptidase (GGT) had remained within normal limits over six months, although anti-mitochondrial antibody (AMA) was shown to be positive. After eight weeks of therapy, the daily dose of rIFN was reduced to 3 million units because of a marked increase of ALP and GGT, although the serum alanine aminotransferase (ALT) was normalized. Four months later, IFN treatment was suspended because of continuous elevation of the ALP and GGT levels, and administration of ursodeoxycholic acid was substituted. Two months later, the ALP and GGT levels returned to the normal range, although ALT was not normalized and HCV-RNA remained positive. This is the first report case that demonstrates IFN treatment potentially exacerbates PBC associated with chronic active hepatitis C. It is important for treating physicians to keep this association in mind.
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PMID:Exacerbation of primary biliary cirrhosis during interferon-alpha 2b therapy for chronic active hepatitis C. 778 37

We developed a sensitive enzyme-linked immunosorbent assay (ELISA) for serum ornithine carbamoyltransferase (OCT) protein, and examined serum OCT concentrations in patients with various liver diseases. OCT concentrations were markedly elevated in cases of hepatic encephalopathy, 'acute on chronic', and those with the acute phase of acute hepatitis, moderately in chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis, and slightly in those with a fatty liver. High percentages (92-98%) of patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma had higher than normal concentrations of serum OCT protein. There was a close correlation with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and moderate correlations with those of mitochondrial AST, glutamate dehydrogenase and gamma-glutamyltranspeptidase. The OCT/ALT ratio was higher in patients with liver cirrhosis than in those with chronic hepatitis (p < 0.001), and was still higher in cases of hepatocellular carcinoma (p < 0.05). In 2 patients with 'acute on chronic' disease, OCT concentrations decreased similarly with or more rapidly than AST or ALT activities after admission. In 2 patients with hepatic encephalopathy, the OCT concentrations changed similarly with AST and ALT activities. This OCT ELISA system will aid in diagnosing various liver diseases and in the follow-up of the patients, and the OCT/ALT ratio may serve for a differential diagnosis of liver diseases.
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PMID:Clinical evaluation of serum ornithine carbamoyltransferase by enzyme-linked immunosorbent assay in patients with liver diseases. 778 67

The beneficial effects of ursodeoxycholic acid (UDCA) in patients with primary biliary cirrhosis led to therapeutic trials with this bile acid for the treatment of PSC. In two prospective placebo-controlled trials, UDCA led to a significant improvement of AP, GGT, ALT, AST, and, in one study, also of serum bilirubin. In both studies liver histology improved significantly, mainly due to a decrease of cellular infiltrates in portal triads. Pruritus and fatigue improved in approximately one-third of the patients, but, compared to placebo, this effect was not significant. In a follow-up study after on average 3.1 years of UDCA treatment, 7/43 of the patients with stages I-IV disease developed a stenosis of the common bile duct which was effectively treated by endoscopic dilatations. Of 57 patients with PSC included since 1987 in the study, 14 dropped out and of these in 10 information on the outcome is available. In patients treated by UDCA and, whenever necessary, by endoscopic dilatations, the frequency of transplantations was significantly reduced in comparison to patients who dropped out of the study. Bile duct carcinoma developed in 5% of our patients. The data indicate that treatment of patients with PSC with UDCA and by endoscopic dilatations of common duct stenoses is promising. In patients with endstage disease, the only effective therapy is liver transplantation. Therefore, the early diagnosis of the disease seems very important.
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PMID:Ursodeoxycholic acid therapy in treatment of primary sclerosing cholangitis. 782 79


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