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)

Nonalcoholic fatty liver disease (NAFLD) is most often associated with obesity, type II Diabetes mellitus, hyperlipidemia and chronic viral hepatitis C. The spectrum of changes encompasses fatty liver, steatohepatitis, liver fibrosis and cirrhosis. Most patients are asymptomatic. The aminotransferases are only slightly elevated (ALT > AST). Grade of inflammation and stage of fibrosis can be assessed accurately only by histologic examination of liver biopsy. In most cases prognosis is favourable but in a subgroup of patients NAFLD may progress to cirrhosis. Recent data suggest that up to 70% of cryptogenic cirrhoses are accounted for by nonalcoholic steatohepatitis. At the moment therapeutic modalities of proven value are not available.
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PMID:[Nonalcoholic fatty liver]. 1193 60

It has been proposed that liver dysfunction may contribute to the development of type 2 diabetes. The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma -glutamyltranspeptidase [GGT]) are associated with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO] during the low-dose insulin infusion of a hyperinsulinemic clamp) and acute insulin response (AIR) (25-g intravenous glucose challenge). Sixty-three subjects developed diabetes over an average follow-up of 6.9 +/- 4.9 years. In 224 subjects, who remained nondiabetic, follow-up measurements of M and AIR were available. At baseline, ALT, AST, and GGT were related to percent body fat (r = 0.16, 0.17, and 0.11, respectively), M (r = -0.32, - 0.28, and -0.24), and HGO (r = 0.27, 0.12, and 0.14; all P < 0.01). In a proportional hazard analysis with adjustment for age, sex, body fat, M, and AIR, higher ALT [relative hazard 90th vs. 10th centiles (95% CI): 1.9 (1.1-3.3), P = 0.02], but not AST or GGT, predicted diabetes. Elevated ALT at baseline was associated prospectively with an increase in HGO (r = 0.21, P = 0.001) but not with changes in M or AIR (both P = 0.1). Higher ALT concentrations were cross-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver in the pathogenesis of type 2 diabetes.
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PMID:High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. 1203 78

Nonalcoholic steatohepatitis (NASH) is a disorder characterized by hepatic steatosis, inflammation, and fibrosis. Leptin is an adipocyte-derived antiobesity hormone that in rodents prevents "lipotoxicity" by limiting triglyceride accumulation and also regulates matrix deposition (fibrosis) during wound healing. We therefore determined serum leptin levels in patients with NASH to determine whether relationships existed between leptin levels and severity of hepatic steatosis or fibrosis. We used a radioimmunoassay to determine serum [total] leptin concentrations in 27 men and 20 women with NASH and 47 controls matched for gender and body mass index (BMI; and partly for age). Serum leptin values were correlated with hepatic steatosis, fibrosis, and inflammation (each categorized semiquantitatively on liver histology), and with anthropometric indices, serum lipids, glucose, insulin, c-peptide, and alanine aminotransferase (ALT) levels. Compared with the controls, mean serum leptin levels were raised in both men and women with NASH (men 14 +/- 11 ng/mL vs. 7.2 +/- 4.1 ng/mL, P =.003; women 35 +/- 16 ng/mL vs. 15 +/- 8.2 ng/mL, P <.001). Leptin values correlated with serum c-peptide levels but not with BMI. In a multivariate analysis, serum leptin (P =.027), serum c-peptide (P =.001), and age (P =.027) were selected as independent predictors of the severity of hepatic steatosis. However, serum leptin was not an independent predictor of hepatic inflammation or fibrotic severity. In conclusion, hyperleptinemia occurs in NASH and is not explained simply by gender, obesity, or the presence of type 2 diabetes. Furthermore, leptin levels correlate directly with the severity of hepatic steatosis but not with inflammation or fibrosis. We propose that the relationship between leptin and steatosis reflects a pathogenic role of leptin in hepatic insulin resistance and/or a failure of the antisteatotic actions of leptin ("peripheral leptin resistance").
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PMID:Serum leptin in NASH correlates with hepatic steatosis but not fibrosis: a manifestation of lipotoxicity? 1214 49

Abnormal circulating levels of hepatic enzymes are frequently found in subjects displaying hyperlipidemia or obesity or both. At present, there is a paucity of information on the principal cardiovascular risk factors that are associated with elevated plasma levels of hepatic enzyme activity in hyperlipidemic patients. We analyzed the potential relationships between serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) and cardiovascular and metabolic risk factors in a cohort of 8,501 men and women referred to our outpatient clinic for hyperlipidemia by their general practitioner. In this cohort, 27.6% of patients displayed serum levels of ALT above the upper limit of normal values. Both men and women who exhibited ALT levels superior to the upper limit of the normal range had elevated systolic (SBP) and diastolic blood pressure (DBP), body mass index (BMI), alcohol intake, and serum levels of blood glucose, uric acid, total cholesterol, and triglycerides (P <.0035 for all parameters). In a multivariate analysis, BMI, uric acid, and blood glucose remained significantly associated with ALT levels in men and women. We conclude that cardiovascular and metabolic features characterizing the plurimetabolic syndrome, including serum uric acid levels, are associated with significant elevation of hepatic enzyme activities. Because these abnormalities may not only be reversible but also associated with a poor prognosis, further studies are needed to identify those dyslipidemic patients who are at risk for the development of severe hepatic tissue damage.
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PMID:A constellation of cardiovascular risk factors is associated with hepatic enzyme elevation in hyperlipidemic patients. 1214 84

The progression of fibrosis in chronic hepatitis C determines the ultimate prognosis and thus the need and urgency of therapy. Fibrogenesis is a complex dynamic process, which is mediated by necroinflammation and activation of stellate cells. The liver biopsy remains the gold standard to assess fibrosis. Scoring systems allow a semiquantitative assessment and are useful for cross-sectional and cohort studies and in treatment trials. The rate at which fibrosis progresses varies markedly between patients. The major factors known to be associated with fibrosis progression are older age at infection, male gender, and excessive alcohol consumption. Viral load and genotype do not seem to influence significantly the progression rate. Progression of fibrosis is more rapid in immunocompromised patients. Hepatic steatosis, obesity, and diabetes may also contribute to more rapid progression of fibrosis. There are no tests that reliably predict the rate of progression of fibrosis in an individual patient. High serum alanine aminotransferase (ALT) levels are associated with a higher risk of fibrosis progression, and worsening of fibrosis is uncommon in patients with persistently normal serum aminotransferase levels. Serum markers for fibrosis are not reliable and need to be improved and validated. Liver biopsy provides the most accurate information on the stage of fibrosis and grade of necroinflammation, both of which have prognostic significance. Repeating the liver biopsy, 3 to 5 years after an initial biopsy is the most accurate means of assessing the progression of fibrosis.
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PMID:Fibrosis and disease progression in hepatitis C. 1240 76

The purpose of this study was to clarify the clinicopathological features of nonalcoholic steatohepatitis (NASH) and identify risk factors for severe hepatic fibrosis. MATERIALS AND METHODS: Eighty-one patients with biopsy-proven NASH were studied. In all patients, the diagnosis of NASH was established on the basis of following criteria: (1) the presence of steatosis, lobular inflammation, and ballooning degeneration on liver biopsy, (2) intake of less than 20 g of ethanol per week, and (3) appropriate exclusion of other liver diseases. RESULTS: The median age was 54 years (range: 21-82 years) and 41 patients were women (51%). Obesity was present in 58 patients (72%), while 25 patients (31%) had diabetes mellitus and 33 patients (41%) had hyperlipidemia. Histologically, 58 patients (72%) had trivial to moderate fibrosis, 6 patients (7%) had bridging fibrosis, and 17 patients (21%) had established cirrhosis. Multiple logistic regression analysis assessed clinical, laboratory and histological factors showed that the risk factors for fibrosis were a low platelet count (P=0.0016), a high AST/ALT ratio (P=0.0229), and the presence of Mallory bodies (P=0.0209). To exclude factors that were a consequence of liver cirrhosis, variables included in the multiple logistic analysis were age, gender, diabetes, obesity, and hyperlipidemia. This showed that older age (P=0.0037) and the absence of hyperlipidemia (P=0.0150) were risk factors for fibrosis. CONCLUSIONS: We found that a low platelet count, a high AST/ALT ratio, and the presence of Mallory bodies were significant predictors of severe liver fibrosis.
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PMID:Nonalcoholic steatohepatitis: risk factors for liver fibrosis. 1247 42

The influence of the "shukko" (temporary transfer) work system on health was examined. "Shukko" is a Japanese individual work system. The life-time employment system was general in Japan. "Shukko" work system was devised to reduce the number of personnel in Japan. "Shukko" personnel belong to their present company but they must do the work of another company. Generally, the disadvantages of "shukko". Personnel are greater than in former "shukko" The subjects are 483 office workers in a certain industrial company. 143 workers work in a subsidiary of this company (Age: 42.2 +/- 5.5) (strategic shukko group), 30 workers work in the other company, having resigned their administrative post in the head office (55.6 +/- 2.1) (Demotion by the manager shukko group), and 310 workers work in the head office of this company (41.8 +/- 5.2) (head office working group). The medical examination results (degree of obesity, systolic blood pressure (SBP), GPT, GGTP, total cholesterol, triglyceride (TG), fasting blood sugar (FBS), uric acid (UA), electrocardiography (ECG), and gastrography were compared by mean of multiple regression analysis. In the "Demotion by the manager shukko" group, the average age and SBP were higher than in the other groups. (p < 0.0001). The "strategic shukko" group was compared with the "head office working" group. There is no significant difference in average age. The average SBP (p < 0.001) and FBS (p < 0.0001) of the "head office working" group was significantly higher than those of the "strategic shukko" group. ECG findings were more serious in the "Demotion by the manager shukko" group than in the other groups (p < 0.0001). There is a significant correlation between SBP and "degree of obesity, FBS and UA" (p < 0.0001). There is significant correlation between FBS and "GGTP, SBP, UA, GPT and TG" (p < 0.0001). And there is significant correlation between ECG findings and "working form and SBP" (p < 0.05). The prevention and early diagnosis of geriatric diseases is important for the "Demotion by the manager shukko" group, and their average age is older than that of the other groups. A problem with the head office working group is obesity. In this group it is important to take into consideration life related diseases. The workers complaint a lot in the "strategic shukko" group, but there are no abnormal findings. We think that their complaints are due to their mental stress. In this group measuring mental stress is important.
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PMID:[Investigation of the health condition of the "shukko" person in a certain Japanese company]. 1251 34

Raised serum level of transaminases aspartate (aminotransferase and alanine aminotransferase) is a frequent situation in medical practice. It is considered as moderate when the level is under 10 times normal and as chronic when it lasts for more than 6 months. The most common etiologies for chronically elevated transaminases are alcohol use, viral hepatitis, liver steatosis, diabetes, obesity and medications. Many non invasive tests, including history, physical examination, blood tests (markers for hepatitis A and B, muscular enzymes), and imaging procedures (abdominal ultrasonography) are usually done and lead to a correct diagnosis in 80% of patients. When the diagnosis cannot be determined non invasively a liver biopsy is recommended in order to make diagnosis, to evaluate the prognosis and to start an adapted treatment.
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PMID:[Interpretation of hypertransaminasemia]. 1253 25

Insulin resistant metabolic syndrome is a major clinical disorder including hyperlipidaemia, hypertension, impaired glucose tolerance and/or type 2 diabetes and central obesity, which are well established cardiovascular risk factors. We report the case of a 61-year-old woman who developed severe hypercholesterolaemia and hypertriglyceridaemia after liver transplantation. In her forties she had hypertension, mixed hyperlipidaemia, mild hyperglycaemia and moderate abdominal obesity, suggesting the presence of the metabolic syndrome. She had liver enzyme elevation and severe steatosis and hepatomegaly at ultrasonography. At age 52, cryptogenic liver cirrhosis was diagnosed and rapidly progressing liver failure developed. In 1992 she underwent liver transplantation. Seven years after transplant the patient had abdominal obesity, high blood pressure, marked hypercholesterolaemia, hypertriglyceridaemia and moderate elevation of alanine aminotransferase. She also had impaired glucose tolerance and markedly increased basal and post-glucose load plasma insulin levels. Steatohepatitis was demonstrated by serial liver biopsies. This is the first case that reports the recurrence of the metabolic syndrome following liver transplantation. We postulate that metabolic syndrome may have promoted fatty liver and subsequent progression to end stage liver disease. We also stress the need for careful management of the metabolic syndrome in order to decrease the long-term risk for cardiovascular disease.
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PMID:Recurrence of insulin resistant metabolic syndrome following liver transplantation. 1254 3

Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat ethanol-containing food. Delivery of recombinant adiponectin into these mice dramatically alleviated hepatomegaly and steatosis (fatty liver) and also significantly attenuated inflammation and the elevated levels of serum alanine aminotransferase. These therapeutic effects resulted partly from the ability of adiponectin to increase carnitine palmitoyltransferase I activity and enhance hepatic fatty acid oxidation, while it decreased the activities of two key enzymes involved in fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase. Furthermore, adiponectin treatment could suppress the hepatic production of TNF-alpha and plasma concentrations of this proinflammatory cytokine. Adiponectin was also effective in ameliorating hepatomegaly, steatosis, and alanine aminotransferase abnormality associated with nonalcoholic obese, ob/ob mice. These results demonstrate a novel mechanism of adiponectin action and suggest a potential clinical application of adiponectin and its agonists in the treatment of liver diseases.
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PMID:The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. 1284 63


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