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Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized health problem. Increased fat accumulation in the liver is observed in 20-30% of the population in the Western world, and in approximately 10% of this cohort it is associated with nonalcoholic steatohepatitis, which is characterized by inflammation and fibrosis. Disease presentation of NAFLD ranges from asymptomatic disease to cirrhosis with the complication of liver failure and hepatocellular carcinoma. NAFLD is suspected on the basis of various clinical aspects (an elevated alanine aminotransferase concentration, presence of obesity and diabetes) that alone are not sufficient to establish diagnosis or prognosis. The major diagnostic procedure is liver biopsy, which allows assessment of liver injury. In most cases, NAFLD is associated with insulin resistance, which is therefore the target of most current NAFLD treatment modalities. Various treatment strategies such as weight loss and/or exercise, thiazolidinediones, metformin, lipid-lowering agents and antioxidants have been studied. So far, no single intervention has convincingly improved liver histology. It is recommended that patients at high risk of developing advanced liver disease, and who are not part of controlled studies, should receive nutritional counseling and take physical exercise to achieve moderate weight loss and improve insulin sensitivity.
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PMID:Treatment strategies in nonalcoholic fatty liver disease. 1626 56

It is generally accepted that non-alcoholic fatty liver disease will be the most frequent liver disease in the near future and that the management of patients with non-alcoholic fatty liver disease will be a challenge for hepatologists in the next decades. Non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome, in which insulin resistance plays a crucial role. Although steatosis will often not progress to severe liver disease, in some patients, it results in cirrhosis and even hepatocellular carcinoma. Therefore, it is important to identify those patients at risk for developing fibrosis. Age, diabetes, obesity and hypertriglyceridaemia are independent risk factors for fibrosis in patients with elevated serum alanine aminotransferase levels and steatosis on ultrasound. The presence of multiple metabolic disorders increases the risk. Apart from diet, exercise and correction of underlying metabolic abnormalities, no specific treatment is available at the moment. Theoretically, thiazolidinediones are an attractive way to treat non-alcoholic fatty liver disease, because they improve insulin resistance. Some preliminary studies with thiazolidinediones were encouraging, as steatosis, inflammation and fibrosis improved in a substantial number of patients. Although no serious side effects occurred in the pilot studies, we should look vigilantly for hepatotoxicity, as the first generation thiazolidinediones proved to be toxic for the liver.
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PMID:Review article: the treatment of non-alcoholic steatohepatitis with thiazolidinediones. 1626 63

The effect of diabetes mellitus on lipid metabolism is well established. The association of hyperglycaemia with an alteration of lipid parameters presents a major risk for cardiovascular complications in diabetes. Many secondary plant metabolites have been reported to possess lipid-lowering properties. The present study was designed to examine the potential anti-hyperlipidaemic efficacy of the ethanolic extract from Aloe vera leaf gel in streptozotocin (STZ)-induced diabetic rats. 2. Oral administration of Aloe vera gel extract at a dose of 300 mg/kg bodyweight per day to STZ-induced diabetic rats for a period of 21 days resulted in a significant reduction in fasting blood glucose, hepatic transaminases (aspartate aminotransferase and alanine aminotransferase), plasma and tissue (liver and kidney) cholesterol, triglycerides, free fatty acids and phospholipids and a significant improvement in plasma insulin. 3. In addition, the decreased plasma levels of high-density lipoprotein-cholesterol and increased plasma levels of low-density lipoprotein-and very low-density lipoprotein-cholesterol in diabetic rats were restored to near normal levels following treatment with the extract. 4. The fatty acid composition of the liver and kidney was analysed by gas chromatography. The altered fatty acid composition in the liver and kidney of diabetic rats was restored following treatment with the extract. 5. Thus, the results of the present study provide a scientific rationale for the use of Aloe vera as an antidiabetic agent.
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PMID:Beneficial effects of aloe vera leaf gel extract on lipid profile status in rats with streptozotocin diabetes. 1648 67

Fruits and vegetables contain numerous antioxidants such as carotenoids, vitamins, and phenolic phytochemicals. Recent studies have demonstrated that antioxidants may reduce the risk for diabetes or its complications. In this study, we investigated the effects of the chronic administration of Satsuma mandarin fruit on an antioxidant defense system in streptozotocin (STZ)-induced diabetic rat liver. After a ten-week administration of Satsuma mandarin, antioxidant enzymes and glutathione levels in the liver were evaluated. The superoxide dismutase (SOD), catalase, and glutathione-peroxidase (GPx) activities, and glutathione level in the STZ-induced diabetic rats liver decreased significantly compared with those in the age-matched normal rats. The glutathione-reductase (GR) activities did not differ significantly between these two groups. In contrast, the SOD, GR, and glutathione levels in the Satsuma mandarin (1% or 3%) diet-fed STZ-diabetic rat livers were significantly higher than those in the normal diet-fed STZ-diabetic rat livers. In addition, although the serum alanine aminotransferase and gamma-glutamyl-aminotransferase concentrations of normal diet-fed STZ-diabetic rats were significantly higher than those of the age-matched normal rats, these increments of serum liver enzymes were diminished by the chronic administration of Satsuma mandarin. These results suggest that Satsuma mandarin may act as a suppressor against liver cell damage and inhibit the progression of liver dysfunction induced by chronic hyperglycemia.
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PMID:Chronic administration of Satsuma mandarin fruit (Citrus unshiu Marc.) improves oxidative stress in streptozotocin-induced diabetic rat liver. 1650 75

Several studies have reported an association between markers of liver injury, including elevated concentrations of alanine aminotransferase (ALT) aspartate aminotransferase (AST), and prospective risk of type 2 diabetes. We therefore examined the relationship between ALT and AST on the one hand, and serum adiponectin and highly sensitive CRP on the other, both of which have been reported to be associated with prospective risk of type 2 diabetes; we also tested for variable components of metabolic syndrome in 198 male college students aged 18-20 years. ALT showed a positive relationship with percentage body fat (r = 0.19, p = 0.02), serum leptin (r = 0.21, p = 0.01), LDL cholesterol (r = 0.29, p = 0.0003), triglyceride (r = 0.28, p = 0.0004) and apolipoprotein B (r = 0.35, p < 0.0001) even after adjustment for body mass index (BMI). Although there was a significant relationship with serum insulin, adiponectin (inversely), homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure, HDL cholesterol (inversely) and LDL particle diameter in simple regression analysis, significance disappeared after adjustment for BMI. In contrast, CRP (r = 0.16, p = 0.04) was associated with ALT after adjustment for BMI, although simple regression analysis revealed no association between the two. Relationships were smaller for AST, and significance disappeared after adjustment for BMI. Multiple regression analysis excluding lipid variables revealed significant and independent associations of ALT with adiponectin and percentage body fat. In a model including lipid variables, apolipoprotein B emerged as an independent predictor of ALT in addition to adiponectin and percentage body fat. These variables explained 29 % of ALT variability. In conclusion, serum ALT levels were associated with leptin and CRP as well as many components of the insulin resistance syndrome in young healthy men. Adiponectin, apolipoprotein B and percentage body fat emerged as significant and independent predictors of ALT. Since adiponectin and chronic subclinical inflammation have been reported to predict the development of type 2 diabetes and since abnormalities in apolipoprotein B metabolism occur in the early course of insulin resistance, these findings may be compatible with the association between liver markers and risk of diabetes.
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PMID:Serum alanine aminotransferase is associated with serum adiponectin, C-reactive protein and apolipoprotein B in young healthy men. 1652 13

The purpose of this study was to examine the short-term effects of diet containing 0.1% (m/m) of acarbose in standard laboratory chow on specific liver enzyme activities: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in control and diabetic CBA mice. Diabetes was induced by intravenous injection of alloxan monohydrate in a dose of 75 mg kg(-1) mouse body mass seven days before the treatment with acarbose. There were four groups of CBA mice in the experiment: control (C) mice (n = 6) and diabetic (D) mice (n = 8) fed standard chow; control (C/A-100) mice (n = 8) and diabetic (D/A-100) mice (n = 8) fed standard chow containing 0.1% acarbose. Diabetes induced a decrease of the ALT catalytic activities to 69.6% of the control value. A similar level of decreased ALT catalytic activity was detected in the liver of control and diabetic mice fed chow containing 0.1% acarbose. No changes in the specific and total activities of AST in the liver of experimental groups were observed.
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PMID:Effect of acarbose on alanine aminotransferase and aspartate aminotransferase activities in the liver of control and diabetic CBA mice. 1661 38

A retrospective cohort study involving 29 Japanese patients with autoimmune hepatitis (AIH) was performed to clarify factors that predict the efficacy of prednisolone and the occurrence of various serious adverse effects. Independent predictors were identified by logistic analysis and with use of the Cox proportional hazard model. Responses to prednisolone were noted in 28 patients, who were classified into the complete remission group (52%) or the relapse group (48%). Multivariate analysis identified alanine aminotransferase, alkaline phosphatase, and immoglobulin G levels as independent predictors of relapse. The adverse effects most frequently observed were diabetes mellitus (37.9%), psychiatric/ neurologic symptoms (34.5%), and circulatory symptoms (34.5%). Predictive factors included lactate dehydrogenase, albumin, and fasting blood glucose levels for diabetes mellitus, alkaline phosphatase and C-reactive protein for psychiatric/ neurologic symptoms, and autoimmune hepatitis score and lactate dehydrogenase for circulatory symptoms. Selection of an optimal treatment method for individual patients may be possible after the risks of relapse and adverse effects have been estimated.
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PMID:Efficacy and safety of prednisolone in patients with autoimmune hepatitis. 1664 9

For a long time, hepatic steatosis was believed to be a benign condition. Only recently, liver steatosis, also termed non-alcoholic fatty liver disease (NAFLD), has gained much interest. In most cases of NAFLD, a condition regarded as the hepatic component of the metabolic syndrome, the enzyme alanine aminotransferase (ALT) is elevated and consequently has been used as a marker for NAFLD. More recently, several cross-sectional and prospective studies have demonstrated associations of this liver enzyme with features of the metabolic syndrome and type 2 diabetes mellitus. This review discusses the biochemical and metabolic properties of ALT, its applicability as a marker of NAFLD and describes its possible role in the pathogenesis of the metabolic syndrome and type 2 diabetes mellitus and subsequent cardiovascular disease. In addition, treatment strategies to ameliorate NAFLD and the associated risks are discussed.
Diabetes Metab Res Rev
PMID:Alanine aminotransferase as a marker of non-alcoholic fatty liver disease in relation to type 2 diabetes mellitus and cardiovascular disease. 1682 76

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins are the most successful cardiovascular drugs of all time. By interrupting cholesterol synthesis in the liver, they activate hepatocyte low-density lipoprotein (LDL) receptors and produce consistent and predictable reductions in circulating LDL cholesterol with resulting reproducible improvements in cardiovascular risk by retarding or even regressing the march of atherosclerosis in all major arterial trees (coronary, cerebral and peripheral). Clinical trials have demonstrated their capacity not only to extend life, but also to improve its quality by retarding the progression of diabetes mellitus and chronic renal disease and by enhancing central and peripheral blood flow. They are amongst the most extensively investigated pharmaceutical agents in current clinical use. In cardiovascular end-point trials they have proven ability to help prevent that first and all important myocardial infarction and to reduce the likelihood of a recurrence in those who do succumb. They are equally effective in men and women of all ages and at all levels of cardiovascular risk, whether caused by hypercholesterolaemia, hypertension, cigarette smoking, diabetes mellitus or the metabolic syndrome. In addition, they improve the outlook of patients with familial hypercholesterolaemia whose LDL receptor function is deficient or defective; and all of this comes at minimal risk to the recipient. Their most important potential side effect is myopathy, which on very rare occasions may lead to rhabdomyolysis. Clinical experience shows that myopathic symptoms with creatine kinase levels raised to more than 10 times the upper limit of normal is seen in <0.01% of recipients and progression to fatal rhabdomyolysis because of renal failure has been recorded in only 0.15 cases per million prescriptions. Liver function abnormalities are also, rarely, seen. Again, the frequency of raised aspartate or alanine aminotransferase to more than three times the normal limit is encountered in no more than 1-2% of all treated patients and is completely reversible upon withdrawal of treatment. Progression to hepatitis or liver failure does not occur. This constellation of benefits with little side effect penalty has resulted in the comparison of statins with antibiotics in the global battle against cardiovascular disease.
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PMID:Who should receive a statin these days? Lessons from recent clinical trials. 1696 68

A 22-year-old Japanese woman presented with general fatigue. Five days later, she demonstrated a body temperature of 39 degrees C and a loss in weight of 5kg. She thereafter became unconscious and was taken to Tomakomai City General Hospital. Urinary ketone body was positive, and plasma glucose was 1063mg/dl. The serum asparate aminotransferase and alanine aminotransferase levels were 158 and 1220IU/l, respectively. An arterial blood gas analysis showed metabolic acidosis. Glycated hemoglobin was 10.9%. Urinary C-peptide immnoreactivity was 11microg/day. Anti-glutamic acid decarboxylase antibody was 12.4U/ml. In general, islet-associated autoantibodies are detectable several years before the development of overt autoimmune diabetes, thus suggesting that an autoimmune reaction against beta-cells had already started in this case. On viral examinations, hepatitis C virus (HCV) antibody was negative, while HCV-RNA was positive. Based on these findings, she was diagnosed to have autoimmune diabetes and acute hepatitis C. In addition, her serum interleukin-18 level was elevated to 506pg/ml. The duration of diabetic characteristic symptoms before diagnosis is usually several weeks in most cases of autoimmune diabetes. However, it was extremely short in this case. Taken together, these findings suggested that the progression of autoimmune diabetes might have been accelerated due to the infection of HCV.
Diabetes Res Clin Pract 2007 Mar
PMID:Acute onset of type 1 diabetes accompanied by acute hepatitis C: the potential role of proinflammatory cytokine in the pathogenesis of autoimmune diabetes. 1711 81


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