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)

Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown. We analyzed data on adults ages 17 yr and older (N = 15,676) from the Third National Health and Nutrition Examination Survey (1988-1994). Participants were classified as having elevated aminotransferase levels if either aspartate aminotransferase or alanine aminotransferase was elevated above normal. Aminotransferase elevation was classified as "explained" if there was laboratory evidence of hepatitis B or C infection, iron overload, or if there was a history of alcohol consumption. Analyses were weighted to provide national estimates. The prevalence of aminotransferase elevation in the United States was 7.9%. Aminotransferase elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection and high transferrin saturation were found in only 31.0% of cases. Aminotransferase elevation was unexplained in the majority (69.0%). In both men and women, unexplained aminotransferase elevation was significantly associated with higher body mass index, waist circumference, triglycerides, fasting insulin, and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05). Aminotransferase elevation was common in the United States, and the majority could not be unexplained by alcohol consumption, viral hepatitis or hemochromatosis. Unexplained aminotransferase elevation was strongly associated with adiposity and other features of the metabolic syndrome, and thus may represent nonalcoholic fatty liver disease.
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PMID:The prevalence and etiology of elevated aminotransferase levels in the United States. 1280 14

Hereditary hemochromatosis is a common inherited disorder characterized by iron overload. A single mutation (C282Y) in the HFE gene is present in 80-95% of cases in populations of northern European extraction. The disorder presents a large phenotypic heterogeneity, and its expression can be influenced by environmental factors. This 1977-2002 study aimed to identify the influence of alcohol consumption on expression of the disease. The authors retrospectively registered 378 C282Y-homozygous patients treated in a blood center of western Brittany, France. In this cohort, 33 patients reported excessive alcohol consumption (8.7%). Those subjects presented significantly increased iron parameters (serum ferritin: 1745.2 vs. 968.7 microg/liter, p< 0.0001; serum iron: 39.9 vs. 36.0 micromol/liter, p = 0.0040; transferrin saturation: 87.1 vs. 80.1%, p = 0.0071) and elevated liver enzymes (alanine aminotransferase: 66.3 vs. 41.1 IU/liter, p = 0.0003; aspartate aminotransferase: 56.2 vs. 34.9 IU/liter, p = 0.0002). Their risk of skin pigmentation was also higher (odds ratio = 3.4, p = 0.0006). Results remained unchanged after adjustment. This study provides precise quantitative data about the impact of alcohol on expression of hereditary hemochromatosis in C282Y-homozygous patients. Excessive alcohol consumption accentuates disease expression and therefore the risk of cirrhosis and cancer. Consequently, these patients should be encouraged to consume very moderate quantities of alcohol.
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PMID:Hereditary hemochromatosis: effect of excessive alcohol consumption on disease expression in patients homozygous for the C282Y mutation. 1285 Dec 25

Thrombocytopenia is a frequent hematological complication in patients with liver cirrhosis, but its pathogenesis is not clearly understood. We evaluated the effect of iron depletion by phlebotomy on platelet count in 62 consecutive iron overloaded patients with liver cirrhosis and thrombocytopenia. After a median follow-up of 30.2 months we observed a significant increase of platelet count in all patients (from mean baseline levels of 110.1 up to 168.22109/l at the end of follow-up, P<0.001) with platelet count normalization in 42 of them (67.7%). In addition, we observed a significant improvement of serum ALT levels (from pretreatment mean values of 126.7 up to 59.7 U/l at the end of follow-up, P<0.001) along with the reduction of serum ferritin levels and transferrin saturation during phlebotomy. Different pathogenetic mechanisms involving both humoral (erythropoietin and thrombopoietin, TPO) and physical (portal hypertension and hypersplenism) factors are here discussed to explain the platelet count increase following phlebotomy. Our results show that phlebotomy is effective not only in lowering iron overload, but also in improving liver function and thrombocytopenia in patients with liver cirrhosis.
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PMID:Platelet count increase following phlebotomy in iron overloaded patients with liver cirrhosis. 1291 44

Alcohol biomarkers include tests indicative of acute or chronic alcohol consumption (state markers), and markers of a genetic predisposition to develop alcohol dependence after chronic exposure (trait markers). While a comprehensive trait marker for alcohol dependence has not been identified, a number of successful state markers for monitoring drinking status are used clinically. These tests provide direct or indirect ways to estimate the amounts of alcohol consumed and the duration of ingestion, and to detect any harmful effects on body functions resulting from long-term misuse. The most obvious method to prove recent drinking is by demonstrating the presence of ethanol in body fluids or breath, but, because ethanol is cleared fairly rapidly from the body, this method is limited to detect only very recent drinking. Measurement of urinary 5-hydroxytryptophol or ethyl glucuronide provide more sensitive methods to disclose recent drinking, because their washout constants are much longer than for ethanol. The liver functions test (GGT, AST and ALT in serum) and the mean corpuscular volume of erythrocytes (MCV) are among the standard diagnostic tools used to identify chronic alcohol exposure. The main disadvantage with these measures is that they have low sensitivity for recent excessive intake, and that raised levels may result from several causes besides heavy drinking, implying a low specificity for alcohol. Carbohydrate-deficient transferrin (CDT), which refers to changes in the carbohydrate composition of serum transferrin, is a more specific marker for identifying excessive alcohol consumption and monitoring abstinence during outpatient treatment. The alcohol biomarkers improves knowledge of drinking patterns in both individuals and populations, and they are also valuable tools for the objective evaluation of treatment efforts. Alcohol markers have, for example, found uses in early identification of at-risk and harmful drinking, and they help to monitor abstinence and relapse in response to outpatient treatment.
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PMID:Biological markers in alcoholism. 1458 1

Hepatitis C virus (HCV) infection is a common cause of liver disease in thalassemia major patients in Western, especially Mediterranean, countries. Its significance in thalassemic patients from Southeast Asia has not been critically evaluated. In this report, we describe our study of the prevalence of HCV infection among Thai patients with thalassemia. The relationships of the infection to blood transfusion and the infection's effects on liver function have also been determined. Of the 104 patients studied, 21 (20.2%) tested positively by enzyme immunoassay for anti-HCV antibody, whereas only 2 patients (2%) had the hepatitis B surface antigen. There was no significant relationship between the presence of anti-HCV antibodies and the number and frequency of blood transfusions. In fact, 2 patients (10%) who tested positive for anti-HCV antibodies had never received transfusions. Patients with anti-HCV antibodies had significantly abnormal liver functions, such as higher levels of serum aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) and lower levels of serum albumin, compared with patients without anti-HCV antibodies (P = .021, .017, and .004, respectively). However, there were also significant correlations between iron status as indicated by transferrin saturation or serum ferritin levels and SGOT, SGPT, and gamma-glutamyltransferase (GGT) levels. Moreover, abnormal liver function as represented by elevated levels of SGOT, SGPT, GGT, and serum alkaline phosphatase was observed more frequently in patients with iron overload than in patients with a lower degree of iron burden. The presence of HCV did not alter the effects of iron overload on liver function. The findings suggest that both HCV and iron overload are the main causes of abnormal liver function in Thai patients with thalassemia. The treatment of both problems, if coexisting in patients with thalassemia, is required to prevent progression to chronic liver disease.
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PMID:Prevalence and clinical significance of hepatitis C virus infection in Thai patients with thalassemia. 1468 98

The biological, clinical and social effects of alcohol abuse call for objective and specific biomarkers of alcohol-related diseases and early detection of alcohol consumers at risk. Alcohol abusers may exhibit several clinical and/or chemical changes. Changes in parameters such as gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and mean corpuscular volume (MCV) may serve as biomarkers of chronic alcoholism. All available biomarkers have two drawbacks. The first is that they indicate adverse effects in a particular organ, but tell little about their aetiology. The second is that they are not sensitive enough to detect abuse before it results in organic impairment. The 1990s have seen the introduction of a new diagnostic biomarker, carbohydrate-deficient transferrin (CDT). Reduced concentrations of this biomarker are found in serum after regular high alcohol intake. Relying on literature and their own clinical experience, the authors conclude that CDT seems to meet the clinical criteria of reliability and specificity.
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PMID:Blood biomarkers of alcohol abuse. 1499 47

The coherence of carbohydrate-deficient transferrin (CDT) as a biomarker of alcohol abuse was investigated with 15 conventional laboratory parameters, with the self-reported medical history and with clinical findings, all previously reported to be associated with chronic alcohol intake. In total, 100 male persons who were at least suspected of abusing alcohol were assessed. Medical history, clinical picture and physical examination were taken, and laboratory parameters regarding blood count, liver enzymes, serum lipids, iron balance, Ig A and uric acid were determined. These data were correlated with the CDT values, the daily ethanol intakes reported, and several findings from medical history and clinical examination. The mean CDT level (mean+/-S.D.) of the entire group was 29.4+/-19.7 U/l. Eighty-one patients admitted a daily ethanol intake of 60 g or more. The ratio AST/ALT (de Ritis ratio) appeared as the best conventional parameter correlated with both CDT and ethanol intake. Mean corpuscular volume (MCV), serum iron, AST and red blood cell count also correlated significantly with CDT. CDT, AST and ferritin correlated significantly with the reported daily ethanol intake. It is concluded that CDT provides a reliable estimate of long-term alcohol intake.
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PMID:Carbohydrate-deficient transferrin (CDT) as a biomarker in persons suspected of alcohol abuse. 1517 58

The IFCC Committee on Plasma Proteins has been investigating regional differences for commonly assayed plasma proteins to determine whether universal reference intervals can be applied. As a part of this study, we launched an Asian project analyzing the concentrations of 13 serum proteins whose values are standardized to CRM470, and five newer analytes: retinol-binding protein (RBP), cystatin C (CysC), light-chain-kappa (L-kappa), and light-chain-lambda (L-lambda). In Tokyo, Seoul, Kuala Lumpur, Hong Kong, Taipei and Shanghai, serum samples were collected from 146 to 415 apparently healthy individuals with nearly equal gender ratios. All assays were performed in Tokyo on a Behring Nephelometer II (BN II). Seven chemical analytes (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gammaGT), creatinine, total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C)) were also measured. These results were used for excluding individuals with possible latent clinical disorders. Positive acute phase reactants were consistently lower, and negative ones were higher, in Tokyo than those in other cities. The most conspicuous difference was observed in C-reactive protein (CRP). There were no regional differences in transferrin, albumin, or CysC. Creatinine was much lower in Tokyo despite comparable CysC levels. ALT and gammaGT were higher in Shanghai, Taipei and Seoul; gammaGT and TG were higher in Shanghai; and HDL-C was higher in Tokyo. Gender-related differences in reference intervals were observed for immunoglobulin (Ig)M, haptoglobin, RBP, transferrin, alpha2-macroglobulin (A2M), transthyretin, alpha1-acid glycoprotein, CysC, and C4 in all cities. Slight age-related differences were observed, irrespective of the region, in IgA and ceruloplasmin (increase) and A2M (decrease). Environmental factors and lifestyle seem to have a great influence on many commonly measured analytes.
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PMID:Diagnostic and epidemiological implications of regional differences in serum concentrations of proteins observed in six Asian cities. 1532 16

Carbohydrate-deficient transferrin (CDT) has been well established as a marker for high alcohol consumption. As studies concerning the specificity of CDT in patients with liver disease have shown controversial outcomes, efforts to illuminate mechanisms leading to impaired CDT specificity in this patient group cannot yet be considered successful. Evidence of apoptosis as examined in 72 alcohol-dependent patients using serum contents of caspase-related M30 monoclonal antibody significantly correlated with aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase but did not influence CDT levels. These results suggest that impairment of CDT specificity is brought forth by derangement of hepatic metabolism rather than by acute hepatocellular damage.
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PMID:CDT values are not influenced by epithelial cell apoptosis in chronic alcoholic patients-preliminary results. 1536 11

A 32-year-old man presented with increases in serum alanine aminotransferase activity, iron concentration, and transferrin saturation, suggestive of hepatic dysfunction and iron overload. In addition, he had unusually low plasma concentrations of LDL-cholesterol and apolipoprotein (apo) B. Hepatic ultrasonography was consistent with fatty liver. On liver biopsy, marked steatosis and moderate to marked iron deposition were observed. The patient was found to carry the HFE C282Y and H63D mutations, which are associated with hereditary hemochromatosis, and the alpha(1)-antitrypsin PiZ variant. An immunoblot of plasma for apoB showed the presence of a truncated apoB species, indicative of familial hypobetalipoproteinemia. DNA sequence analysis revealed that the patient was heterozygous for the apoB-80.5 (c.11040T>G) mutation. This unique case shows an unusual combination of underlying disorders that could all be contributing to liver dysfunction and fatty liver.
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PMID:Liver dysfunction and steatosis in familial hypobetalipoproteinemia. 1551 99


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