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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic insulin resistance is an important underlying cause of the metabolic syndrome that manifests itself in diseases such as diabetes type II, atherosclerosis or non-alcoholic fatty liver disease (NAFLD). In this paper, we summarize comprehensively the current state of knowledge pertaining to the molecular mechanisms that lead to insulin resistance in hepatocytes and sinusoidal liver cells. In hepatocytes, the insulin resistant state is brought about by at least one, but more likely by a combination, of the following pathological alterations: hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Insulin resistance in hepatocytes distorts directly glucose metabolism, especially the control over glucose output into the circulation and interferes with cell survival and proliferation, while hepatic fatty acid synthesis remains stimulated by compensatory hyperinsulinaemia, resulting in steatosis. Very few studies have addressed insulin resistance in sinusoidal liver cells. These cells are not simply bystanders and passive witnesses of the changes affecting the hepatocytes. They are target cells that will respond to the pathological alterations occurring in the insulin resistant state. They are also effector cells that may exacerbate insulin resistance in hepatocytes by increasing oxidative stress and by secreting cytokines such as TNF and IL-6. Moreover, activation of sinusoidal endothelial cells, Kupffer cells and stellate cells will lead to chemo-attraction of inflammatory cells. Finally, activation of stellate cells will set in motion a fibrogenic response that paves the way to cirrhosis.
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PMID:Insulin resistance in hepatocytes and sinusoidal liver cells: mechanisms and consequences. 1751 85

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. It encompasses a wide spectrum of liver lesions, from pure steatosis to end-stage liver disease with cirrhosis and hepatocellular carcinoma. Nonalcoholic steatohepatitis corresponds only to one stage of NAFLD. As NAFLD can be considered a liver manifestation of the metabolic syndrome, its prevalence is high in obese people and in patients who have type 2 diabetes-insulin resistance is one of the key elements of the pathogenesis of NAFLD. This disease is often asymptomatic in the absence of decompensated cirrhosis, but should be suspected in patients with elevated aminotransferase levels or radiological evidence of a fatty liver or hepatomegaly. Liver fibrosis is associated with age over 50 years, obesity, diabetes and high triglyceride levels. Liver biopsy is the only way to assess the histologic features of necrotic inflammation and fibrosis that define nonalcoholic steatohepatitis and to determine its probable prognosis. The prognosis is good for pure steatosis, whereas the presence of necrotic inflammation is associated with a significant risk of progression to cirrhosis and, possibly, hepatocellular carcinoma. Lifestyle changes, such as dietary modifications and exercise, are recommended. To date, there have been very few randomized, placebo-controlled trials of drug treatments for NAFLD.
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PMID:Nonalcoholic fatty liver disease: from pathogenesis to patient care. 1751 90

The increasing prevalence of obesity in Western countries has led to a significant increase of nonalcoholic fatty liver disease (NAFLD) over the past decades. Being part of the metabolic syndrome, NAFLD is thought to be the most frequent cause of elevated liver enzymes in the United States affecting up to one third of the population. NAFLD is also proposed to be the major cause for cryptogenic cirrhosis and hepatocellular cancer of unknown etiology, and thus, represents one of the most important problems for hepatologists in the future. However, the natural course of NAFLD is highly variable and is influenced by both environmental and genetic factors. Polymorphisms in specific genes have been proposed to increase the risk of fibrosis in patients with NAFLD. The present review article summarizes currently available data from genotype-phenotype studies and defines candidate genes that deserve future investigation.
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PMID:The genetics of nonalcoholic fatty liver disease. 1751 29

Nonalcoholic fatty liver disease (NAFLD) is an emerging clinical entity. There is limited data on NAFLD from India. The objective of this article was to review all the published literature on NAFLD from India. The epidemiological studies including prevalence ofNAFLD amongst special groups like in those with unexplained rise in transaminases, diabetes mellitus and cryptogenic cirrhosis, studies on pathogenesis including insulin resistance, iron abnormalities, and studies available for the treatment of such patients have been reviewed. In addition some of the differences between Indian patients and those from the West have been highlighted. Available literature show that majority of Indian patients with NAFLD have overweight or obesity as per Asian Pacific criteria even though they do not have the kind of morbid obesity as seen in patients from the West. Other differences between Indian patients and those from the West include less of metabolic syndrome including its components like diabetes mellitus and hypertension, less of iron abnormalities and HFE gene mutations and mild histological disease at presentation in Indian patients. More data is required to substantiate these findings and to prove if NAFLD patients in India are different at presentation.
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PMID:Nonalcoholic fatty liver disease in India--is it different? 1754 90

Non-alcoholic fatty liver disease (NAFLD) represents one of the most common forms of liver disease and is considered the hepatic manifestation of the metabolic syndrome. Within the NAFLD spectrum, simple steatosis is considered benign, whereas non-alcoholic steatohepatitis (NASH) may progress to cirrhosis. The distinction can be made only by liver biopsy. There is not complete agreement on criteria for diagnosis or the features used for grading and staging lesions. This article reviews some of the studies dealing with the histopathology of NAFLD, with attempts to develop a standardized pathologic scoring system for NASH.
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PMID:Pathologic assessment of non-alcoholic fatty liver disease. 1754 69

Non-alcoholic fatty liver disease (NAFLD) is often associated with features of the metabolic syndrome, carrying an increased risk to develop non-alcoholic steatohepatitis (NASH), the inflammatory form of liver steatosis. Epidemiological data confirm that obesity, diabetes, hypertension and hyperlipidemia are frequently found in NAFLD and worsen its prognosis because of increased risk of fibrotic evolution, eventually leading to liver cirrhosis. Recent studies confirm the close relationship between the metabolic syndrome and liver steatosis, and further support the detrimental role of oxidative stress and lipid peroxidation, which are pathophysiological processes present in both conditions. Novel diagnostic tools and life style modifications together with targeted therapeutic actions are urgently needed for the management of liver dysfunction in course of metabolic syndrome.
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PMID:Non-alcoholic fatty liver disease in the metabolic syndrome. 1762 52

The clinicopathologic spectrum of nonalcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Simple steatosis has a relatively benign clinical course, but NASH can progress to cirrhosis and hepatocellular carcinoma. NAFLD occurs in the absence of significant alcohol use and is considered to be the hepatic manifestation of metabolic syndrome. NAFLD affects approximately 30% of the US population and the incidence seems to be rising as the obesity epidemic continues. At present, the most accurate modality for the diagnosis of NASH is liver biopsy; however, many patients do not have a liver biopsy, and in the absence of more-accurate imaging technologies and serum markers, the diagnosis is frequently one of exclusion. As yet there is no convincingly effective treatment for NAFLD--a multimodal treatment plan that targets obesity, insulin resistance, hyperlipidemia and hypertension might be the best option for these patients.
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PMID:Evaluation and management of obesity-related nonalcoholic fatty liver disease. 1766 92

Nonalcoholic fatty liver disease (NAFLD) refers to the presence of hepatic steatosis not associated with a significant intake of ethanol. Insulin resistance is central to the pathogenesis of NAFLD; thus obesity, diabetes, and the metabolic syndrome are frequently associated with the disease. Consequently, as these metabolic conditions emerge as major health problems in Western society, it is now recognized that NAFLD is the most common chronic liver condition in the Western world. NAFLD is generally asymptomatic, although a minority of patients may present with evidence of progressive liver injury with complications of cirrhosis, liver failure, and hepatocellular carcinoma. Despite being common and potentially serious, relatively little is known about the natural history or prognostic significance of NAFLD. Although diabetes, obesity, and age are recognized risk factors for advanced liver disease, other significant factors leading to progressive liver injury remain to be identified. The treatment of NAFLD focuses upon modifying metabolic risk factors. Insulin-sensitizing and hepatoprotective drugs have been subjected to study trials, but as yet, no agent has conclusively been demonstrated to prevent disease progression. Management is further complicated by the inability to predict which patients will develop liver-related morbidity and thus benefit from treatment.
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PMID:Nonalcoholic fatty liver disease. 1772 49

Non-alcoholic fatty liver disease (NAFLD) is found in individuals who do not drink or abuse alcohol and represents a significant health burden for the general community. NAFLD is often associated with one or more features of the metabolic syndrome and has potential for evolution towards non-alcoholic steatohepatitis (NASH), the necro-inflammatory form of liver steatosis. The most worrisome evolutive events in a subgroup of NASH patients include advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Pathophysiology of NAFLD/NASH is complex, but studies point to a pre-eminent role of oxidative stress and lipid peroxidation in the liver, including early mitochondrial dysfunction. Changes follow an insulin resistance status with a background of a chronic pro-inflammatory status due to an excess of visceral adiposity. Although no established therapy exists for NAFLD/NASH, potential therapeutic approaches are discussed in this review.
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PMID:Present and future therapeutic strategies in non-alcoholic fatty liver disease. 1784 48

Nine patients with hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) (six men and three women, median age 71.5 years) and one patient with intrahepatic cholangiocarcinoma (ICC), a 50-year-old man, in NASH are described. Most patients were associated with obesity, diabetes, hypertension, hypercholesterolemia, or hypertriglyceridemia. Seven patients showed insulin resistance and hyperinsulinemia. All patients except one met the criteria for metabolic syndrome. An HCC or ICC diagnosis was confirmed by tumor biopsy, surgery or autopsy except in two patients, who were diagnosed by computed tomography or hepatic angiography. The underlying liver disease was liver cirrhosis in six patients and chronic liver disease including mild hepatic fibrosis in four patients. The treatment of liver cancers consisted of surgery, radio-frequency ablation (RFA), transcatheter arterial embolization and transcatheter arterial infusion. Although the follow-up period was relatively short (median 27.5 months, average 32.1 months), all postoperative and post-RFA patients have not had a recurrence of HCC to date, except for one patient who had a palliative operation with intra-arterial infusion of anticancer drugs through an implanted reservoir port. Older age and liver cirrhosis are considered risk factors for HCC in NASH, and regular screening of these patients is necessary. Diabetes may contribute to the development of ICC in NASH. Curative therapy (surgery or RFA) and weight loss by the active therapeutic intervention (nutritional care and exercise therapy) after curative therapy may help us improve the prognosis of HCC in NASH.
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PMID:Primary liver cancers with nonalcoholic steatohepatitis. 1787 5


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