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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The majority of patients with nonalcoholic fatty liver disease are overweight and obese, lead relatively sedentary lifestyles, and have underlying insulin resistance. Treatment aimed at improving body weight and activity should be the cornerstone of our therapeutic armamentarium in combating this disease. Evidence suggests that diets low in processed carbohydrates and saturated fats with a goal to achieve a 500- to 1000-calorie/day deficit improve insulin sensitivity, reduce serum aminotransferases, and decrease hepatic steatosis. Encouragingly, improvements are seen with as little as a 5% reduction in body weight. Histopathologic parameters of steatohepatitis also appear to improve with weight loss. Antioxidant supplementation, specifically with vitamin E, may be considered as adjunctive therapy. Other antioxidants and the thiazolidinediones (pioglitazone and rosiglitazone) appear to be efficacious, but larger confirmatory studies are needed to ensure they are safe and beneficial in patients with nonalcoholic steatohepatitis. Novel agents such as renin-angiotensin system inhibitors may eventually prove to be efficacious as well. Future treatment for patients failing to achieve weight loss goals is likely to consist of combination therapy targeting insulin resistance, oxidative stress, and fibrogenesis.
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PMID:New treatments for nonalcoholic fatty liver disease. 1651 31

Lipid peroxidation and secondary cellular injury are the dominant mechanism in the transition from relatively stable hepatic steatosis to potentially progressive steatohepatitis in nonalcoholic fatty liver disease (NAFLD). Oxidation of excessive fatty acids generates free radicals (reactive oxygen species) that damage organelles and stimulate signaling pathways leading to fibrosis and cellular injury. Both antioxidant agents (by breaking the chain reaction of lipid peroxidation) and cytoprotective agents (by stabilizing cellular and organelle phospholipid membranes) may be effective agents in treating an active steatohepatitis through amelioration of the driving force and attenuation of the secondary effects. Here we have reviewed the existing studies on such therapies, including vitamin E, S-adenosylmethionine (SAMe), betaine, and ursodeoxycholic acid. Small trials suggest possible improvement in liver enzymes with the use of these agents in NAFLD. However, controlled studies have not uniformly demonstrated benefit from these agents when compared with control groups treated with diet and weight loss alone, and measurement of reliable histologic endpoints is limited. These agents may show benefit in NAFLD through future larger controlled studies. Particular promise may exist in the use of these agents in combination therapy with ones that target other aspects in the pathogenesis of NAFLD, such as insulin-sensitizing agents.
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PMID:Therapy of NAFLD: antioxidants and cytoprotective agents. 1654 Jul 69

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver disease whose hallmark is the accumulation of large-droplet fat in hepatocytes. This metabolic disorder occurs mainly in overweight or obese individuals. The disease mechanism involves hyperinsulinemia and hepatic insulin resistance, not ethanol abuse. NAFLD may be the hepatic manifestation of the "metabolic syndrome" classically associated with type 2 diabetes mellitus and cardiovascular disease. NAFLD ranges from simple steatosis, which is the least rapidly progressing disorder, to nonalcoholic steatohepatitis to cirrhosis, which can evolve to chronic liver failure. The high prevalence of NAFLD in children has been recognized only in the past 5 to 10 years, as rates of childhood obesity have soared. Accordingly, the best strategies for diagnosis and treatment of childhood NAFLD are a work in progress and remain controversial. Weight reduction through a healthy diet and regular medium-intensity exercise is the mainstay of current treatment. Few research data are available to guide pharmacologic therapy. Certain points regarding management of childhood NAFLD require emphasis: It is a serious liver disease that requires detailed clinical investigation. Other liver diseases causing fatty liver and/or abnormal liver tests, notably Wilson disease and chronic viral hepatitis, need to be excluded. Liver biopsy can provide critical diagnostic and staging information. Associated genetic or endocrine disorders need to be identified. Treatment should begin with a low-glycemic index diet that provides adequate nutrients but is low in harmful fats and eliminates foods causing postprandial hyperglycemia. Initially, this can target two to three problem foods so that it is easy for the adolescent to follow. Regular exercise suited to the capabilities and interests of the teenager should be added to the daily routine. Where possible, a team approach, including a dietician and psychologist, should be utilized, as adolescents do better in a supportive atmosphere. Optimal drug treatment requires further research: current front-runners are vitamin E and metformin. The roles of drugs that alter appetite and bariatric surgery for adolescents with NAFLD have not been determined.
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PMID:Nonalcoholic Fatty Liver Disease (NAFLD): Approach in the Adolescent Patient. 1694 68

Although population prevalence is very difficult to establish, nonalcoholic fatty liver disease (NAFLD) is probably the most common cause of liver disease in the preadolescent and adolescent age groups. There seems to be an increase in the prevalence of NAFLD, likely related to the dramatic rise in the incidence of obesity during the past 3 decades. Despite an increase in public awareness, overweight/obesity and related conditions, such as NAFLD, remain underdiagnosed by health care providers. Accurate diagnosis and staging of nonalcoholic steatohepatitis (NASH) requires liver biopsy. The development of noninvasive surrogate markers and the advancements in imaging technology will aid in the screening of large populations at risk for NAFLD. Two distinct histological patterns of NASH have been identified in the pediatric population, and discrete clinical and demographic features are observed in children with these 2 patterns. The propensity for NASH to develop in obese, insulin-resistant pubertal boys of Hispanic ethnicity or a non-Hispanic white race may provide clues to the pathogenesis of NAFLD in children. The natural history of pediatric NASH has yet to be defined, but most biopsies in this age group demonstrate some degree of fibrosis. In addition, cirrhosis can be observed in children as young as 10 years. While the optimal treatment of pediatric NAFLD has yet to be determined, lifestyle modification through diet and exercise should be attempted in children diagnosed with NAFLD. A large, multicenter trial of vitamin E and metformin is underway as part of the NASH clinical research network.
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PMID:Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications for future research. 1703 14

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-beta, tumor necrosis factor-alpha, degree of steatosis, and gamma-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage.
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PMID:The effect of a silybin-vitamin e-phospholipid complex on nonalcoholic fatty liver disease: a pilot study. 1741 Apr 54

Liver fibrosis may be considered as a dynamic and integrated cellular response to chronic liver injury. The activation of hepatic stellate cells and the consequent deposition of large amounts of extracellular matrix play a major role in the fibrogenic process, but it has been shown that other cellular components of the liver are also involved. Although the pathogenesis of liver damage usually depends on the underlying disease, oxidative damage of biologically relevant molecules might represent a common link between different forms of chronic liver injury and hepatic fibrosis. In fact, oxidative stress-related molecules may act as mediators able to modulate all the events involved in the progression of liver fibrosis. In addition, chronic liver diseases are often associated with decreased antioxidant defenses. Although vitamin E levels have been shown to be decreased in chronic liver diseases of different etiology, the role of vitamin E supplementation in these clinical conditions is still controversial. In fact, the increased serum levels of alpha-tocopherol following vitamin E supplementation not always result in a protective effect on liver damage. In addition, clinical trials have usually been performed in small cohorts of patients, thus making definitive conclusions impossible. At present, treatment with vitamin E or other antioxidant compounds could be proposed for nonalcoholic fatty liver disease (NAFLD), the most frequent hepatic lesion in western countries which can progress to nonalcoholic steatohepatitis and cirrhosis due to the production of large amounts of oxidative stress products. However, although some studies have shown encouraging results, multicentric and long-term clinical trials are needed.
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PMID:Vitamin E in chronic liver diseases and liver fibrosis. 1762 89

Significant disorders of liver metabolic pathways enzymes after high-cholesterol diet could give information on liver steatosis development. This process could probably also be inhibited by some compounds, as examined in rabbits. Forty-two male rabbits were served a high-cholesterol diet (2 g%) (0.67 g/kg b.m./24 h) with addition of d,l-methionine (70 mg/kg b.m./24 h) or seleno-d,l-methionine (12.5 microg/kg b.m./24 h) or alpha-tocopherol (10 mg/kg b.m./24 h) for 3 months to compare the protection effect of used compounds on liver metabolism and steatosis. At the beginning and every month, blood was taken. After the experiment was completed, livers were dissected for histological examinations. The concentration of total cholesterol (t-CH), triacylglycerol (TG), and the activities of aldolase (ALD), sorbitol dehydrogenase (SDH), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined. Plasma t-CH and TG concentrations were significantly higher in all experimental groups vs control group. Blood serum AST and ALT activities did not undergo change but there were observed not significant increase in the CH group vs control group. Activities of SDH, GLDH, and LDH increased in blood serum and decreased in the liver in all experimental groups. Activities of LDH and SDH increased in the liver in the CH+Met group vs CH group. ALD activity decreased in the liver only in the CH and CH+Se groups. This data support a lipotoxic model of cholesterol-mediated hepatic steatosis. Prolonged administration of high-cholesterol diet not only disturbs the structure of cell membranes, which is expressed by decreased activity of enzymes in the liver and the migration of those enzymes to plasma but as well leads to steatosis of the liver, which has been confirmed by histological examinations. The applied compounds appear to have a varying influence upon the activity of enzymes determined in serum and liver. Obtained results showed a beneficial influence of methionine and vitamin E supplementation on liver steatosis development.
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PMID:The influence of methionine, selenomethionine, and vitamin E on liver metabolic pathways and steatosis in high-cholesterol fed rabbits. 1791 70

The aim of this study was to determine if orlistat, an inhibitor of fat absorption, combined with caloric restriction in overweight subjects with nonalcoholic steatohepatitis results in weight loss and improved liver histology. Fifty overweight subjects (body mass index = >or=27) with biopsy proven nonalcoholic steatohepatitis were randomized to receive a 1,400 Kcal/day diet plus vitamin E (800 IU) daily with or without orlistat (120 mg three times a day) for 36 weeks. Liver biopsies were repeated at week 36. Twenty-three subjects in the orlistat/diet/vitamin E group and 18 in the diet/vitamin E group completed the study. The mean age was 47 +/- 9.0 (standard deviation) years and mean body mass index was 36.4 +/- 6.3 kg/m(2). Four subjects were diabetic. The orlistat group lost a mean of 8.3% body weight compared to 6.0% in the diet plus vitamin E group (not significant). Both groups also had similarly improved serum aminotransferases, hepatic steatosis, necroinflammation, ballooning, and nonalcoholic fatty liver disease activity scores. Stratified according to weight loss instead of treatment group, a loss of >or=5% body weight (n = 24) compared to <5% body weight (n = 17) correlated with improvement in insulin sensitivity (P = 0.001) and steatosis (P = 0.015). Comparing subjects who lost >or=9% of body weight (n = 16), to those that did not (n = 25), improved insulin sensitivity (P < 0.001), adiponectin (P = 0.03), steatosis (P = 0.005), ballooning (P = 0.04), inflammation (P = 0.045), and nonalcoholic fatty liver disease activity score (P = 0.009) were seen. Increases in adiponectin strongly correlated with improved ballooning and nonalcoholic fatty liver disease activity score (P = 0.03). Orlistat did not enhance weight loss or improve liver enzymes, measures of insulin resistance, and histopathology. However, subjects who lost >or=5% of body weight over 9 months improved insulin resistance and steatosis, and those subjects who lost >or=9% also achieved improved hepatic histologic changes.
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PMID:Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. 1949 25

Mass spectrometry imaging has been used to map liver biopsies of several patients suffering from nonalcoholic fatty liver disease. This steatosis is characterized by an accumulation of triacylglycerols and diacylglycerols in the liver. Using time-of-flight-secondary ion mass spectrometry (TOF-SIMS) with a bismuth cluster ion source, it has been possible to map lipids in situ at the micrometer scale and to simultaneously characterize their molecular distribution on liver sections. Accumulation of triacylglycerols, diacylglycerols, monoacylglycerols, fatty acids, with the apparition of myristic acid, together with a dramatic depletion of vitamin E and a selective macrovacuolar localization of cholesterol are observed in steatosis areas of fatty livers compared to control livers. These ion species are concentrated in small vesicles having a size of a few micrometers. Moreover, very fine differences in lipid localizations, depending on alkyl acid chain lengths of diacylglycerols and fatty acids, have been found after careful scrutiny of the ion images. Finally, TOF-SIMS has revealed lipid zonation in the normal human liver and accumulation of very similar lipids to those detected in areas of the fatty livers, which are not characterized as steatotic ones by the histological control performed on serial tissue sections.
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PMID:In situ lipidomic analysis of nonalcoholic fatty liver by cluster TOF-SIMS imaging. 1929 90

Nonalcoholic fatty liver disease (NAFLD) is a state of excessive accumulation of fat in the liver of persons whose alcohol intake is lower than the classical level for causing liver damage. When inflammation and fibrosis occur in addition to fatty liver, followed by the development of chronic hepatic dysfunction, the condition is called non-alcoholic steatohepatitis (NASH). Vitamin E possesses antioxidant activity and is effective for NASH, but the mechanism of action is not known. We utilized a methionine-choline deficiency rat model (MCD rats) to investigate the mechanism by which vitamin E improves NASH. In MCD rats, high-dose vitamin E therapy reduced the hepatic content of thiobarbituric acid-reactive substances, but failed to improve liver histopathology. The hepatic content of alpha-tocopherol was also elevated and this might be related to the expression of alpha-tocopherol transfer protein.
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PMID:Children's toxicology from bench to bed--Liver Injury (2): Mechanism of antioxidant therapy for nonalcoholic fatty liver disease. 1957 73


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