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 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance, and is now considered as one of the commonest liver diseases in western countries. It is frequently associated with severe obesity, especially abdominal adiposity, and is intimately related to various clinical and biological markers of the insulin resistance syndrome. Especially, both the prevalence and the severity of liver steatosis are related to male sex, body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. A substantial weight loss following gastroplasty is accompanied by a marked reduction in the prevalence and the severity of the various biological abnormalities of the metabolic syndrome and, concomitantly, by an important regression of liver steatosis in most obese patients. However, in some patients, this rapid and drastic weight loss may result in a mild increase in inflammatory lesions (hepatitis), despite the regression of steatosis, which might result from the rapid mobilization of fatty acids or cytokines from adipose tissue, especially visceral fat. The intimate relationship between NASH and obesity leads to the concept that NASH may be considered as another disease of affluence, as is the insulin resistance syndrome and perhaps being part of it.
Diabetes Metab 2000 Apr
PMID:Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss. 1080 23

Treatment of patients with nonalcoholic fatty liver has typically been focused on the management of associated conditions such as obesity, diabetes mellitus, and hyperlipidemia as well as discontinuation of potentially hepatotoxic drugs. Nonalcoholic fatty liver associated with obesity may resolve with weight reduction, although the benefits of weight loss have been inconsistent. Appropriate metabolic control for patients with diabetes mellitus or hyperlipidemia is always recommended but not always effective in reversing nonalcoholic fatty liver. Promising results of pilot studies evaluating ursodeoxycholic acid, gemfibrozil, betaine, N-acetylcysteine, and alpha-tocopherol suggest that these medications may be of potential benefit in the treatment of patients with nonalcoholic fatty liver. These medications, however, need first to be tested in well-controlled trials with clinically relevant end points and extended follow-up. A better understanding of the pathogenesis and natural history of this condition will help to identify the subset of patients with nonalcoholic fatty liver at risk of progressing to advanced liver disease and, hence, the subgroup of patients who should derive the most benefit from medical therapy. In this article, we review (1) the existing medical therapy for patients with nonalcoholic fatty liver, (2) the emerging data from clinical trials evaluating potentially useful medications, and (3) the potential therapeutic implications of recent studies on the pathogenesis of this liver disease.
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PMID:Treatment of nonalcoholic fatty liver: present and emerging therapies. 1129 99

Non-alcoholic steatohepatitis (NASH) is a form of liver disease resembling alcoholic liver disease in a patient who does not consume significant amounts of alcohol. Since its first description in 1980 it has been recognized with increasing frequency. The natural course is relatively benign, but liver cirrhosis. together with all its sequelae, may develop; sometimes liver transplantation is indicated. NASH should probably be regarded as a two-stage acquired metabolic disorder consisting of the development of the insulin resistance syndrome in a patient with pre-existing metabolic abnormalities. The insulin resistance syndrome may well be the most important metabolic abnormality giving rise to hepatic steatosis. The preexisting metabolic abnormalities can be diverse, and may well be multifactorial and/or polymorphogenetic. A steatotic liver may be more susceptible to the deleterious effects of the pre-existing metabolic abnormalities. Pre-existing metabolic abnormalities of particular interest are increased hepatic iron storage and derangements of lipoprotein metabolism. While awaiting the complete resolution of the pathogenesis, current treatment is largely conservative. Every patient should be encouraged to lose weight and to avoid alcohol and other hepatotoxins. In addition, diabetes, lipid abnormalities and increased iron stores should be looked for.
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PMID:Non-alcoholic steatohepatitis: clinical significance and pathogenesis. 1176 67

Nonalcoholic fatty liver disease is now recognized as the most common liver disease in the United States, with a prevalence of approximately 5% in the general population and up to 25% to 75% in patients with obesity and type II diabetes mellitus. Nonalcoholic fatty liver disease is a clinicopathologic syndrome with a wide spectrum of histologic abnormalities and clinical outcomes. Hepatic steatosis has a benign clinical course. In contrast, nonalcoholic steatohepatitis (NASH) may progress to cirrhosis and liver-related death in 25% and 10% of patients, respectively. Cases occur most commonly in obese, middle-aged women with diabetes. However, NASH may also occur in children and normal-weight men with normal glucose and lipid metabolism. The pathophysiology involves two steps. The first is insulin resistance, which causes steatosis. The second is oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines resulting in NASH. Liver biopsy provides prognostic information and identifies NASH patients who may benefit from therapy. Treatment consists of managing the comorbidities: obesity, diabetes, and hyperlipidemia. Although antioxidant therapy with vitamin E is often used, ursodeoxycholic acid is the only drug that has shown benefit and is the most promising of the drugs currently being investigated. Future therapies will depend on a greater understanding of the pathophysiology and should focus on diminishing fibrosis.
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PMID:Update on nonalcoholic fatty liver disease. 1187 8

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

Nonalcoholic fatty liver disease is emerging as the most common liver disease in North America. The histological spectrum of nonalcoholic fatty liver disease ranges from fatty liver alone to steatohepatitis and to the most serious form--nonalcoholic steatohepatitis (NASH). An increasing body of evidence suggests that NASH is associated with the development of progressive fibrosis and eventually cirrhosis in approximately 20% of cases. These data emphasize the need to develop effective therapy for the treatment of NASH. Cases occur most commonly in obese middle age women with diabetes. However, NASH may also occur in children and normal weight men with normal glucose and lipid metabolism. The pathophysiology involves 2 steps. The first is insulin resistance, which causes steatosis. The second is oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines resulting in NASH. Liver biopsy provides prognostic information and identifies NASH patients who may benefit from therapy. Treatment consists of managing the comorbidities: obesity, diabetes, and hyperlipidemia. Nascent clinical trials suggest that a number of therapies may be beneficial. These include anti-oxidants such as vitamin E and betaine, bile acid therapy with ursodeoxycholic acid, and improved insulin sensitivity with metformin. Another potential therapeutic strategy is the reduction of inflammatory cytokines.
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PMID:Diabetes mellitus, obesity, and hepatic steatosis. 1194 30

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects a high proportion of the world's population. Insulin resistance and oxidative stress play a critical role in the pathogenesis of NAFLD. Clinical, biochemical and imaging studies are of value in the diagnostic evaluation of patients with NAFLD, but liver biopsy remains the most sensitive and specific means of providing important diagnostic and prognostic information. Simple steatosis has the best prognosis within the spectrum of NAFLD, but NAFLD has the potential to progress to steatohepatitis, fibrosis and even cirrhosis. No effective medical therapy is currently available for all patients with NAFLD. In patients with diabetes mellitus and hyperlipidemia, appropriate metabolic control is always recommended, but rarely effective in resolving the liver disease. Weight reduction, when achieved and sustained, may improve the liver disease, although the results with weight loss have been inconsistent. Pharmacological therapy aimed at the underlying liver disease holds promise. Several medications with different mechanisms of action and potential benefit are currently being evaluated in clinical trials. Liver transplantation is a life-extending therapeutic alternative for patients with end-stage NAFLD, but NAFLD may recur after liver transplantation.
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PMID:Non-alcoholic fatty liver disease. 1200 Jun 5

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.
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PMID:Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. 1229 56

Nonalcoholic fatty liver disease (NAFLD) is common in obese children and is a growing problem, given the increase in prevalence of obesity. NAFLD is also associated with diabetes, insulin resistance, hypercholesterolemia, and hypertriglyceridemia. Although mostly benign, some children with NAFLD develop fibrosis and cirrhosis, which necessitates close monitoring. Chronically elevated plasma liver enzyme levels is the most frequent finding. Ultrasound (US) examination allows confirmation of the diagnosis and it is useful for the follow-up. Gradual and sustained weight reduction is a management option that is worth trying initially. Other modalities of management, although interesting, await evidence as well as information on long-term benefits and effects. Sustained increase of transaminases despite weight reduction is a cause for concern and may require a liver biopsy both to assess severity of liver damage and for prognostic purposes.
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PMID:Nonalcoholic fatty liver disease (NAFLD) in children. 1235 54

Non-alcoholic fatty liver disease (NAFLD) is usually seen in middle-aged women with obesity, non-insulin-dependent diabetes mellitus and/or hyperlipidaemia. NAFLD has also been associated with other conditions. Surgical procedures to treat obesity such as jejunoileal bypass and gastroplasty as well as massive small bowel resection have been associated with NAFLD. Mechanisms such as rapid weight loss, certain nutritional deficiencies and bacterial overgrowth have been proposed. Other nutritional conditions such as extreme malnutrition and total parenteral nutrition can also cause NASH. This can be due to abnormal glucose and fat metabolism, deficiencies like carnitine, essential fatty acid and choline or, in the case of parenteral nutrition, excess of calories, glucose or lipids. Several drugs have also been implicated as well as some inborn errors of metabolism and, more rarely, other diseases.
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PMID:Other disease associations with non-alcoholic fatty liver disease (NAFLD). 1240 45


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