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

Non-alcoholic fatty liver disease (NAFLD) is now recognized as one of the most important causes of chronic liver disease in Western Countries, and is the hepatic manifestation of metabolic syndrome. The prevalence of NAFLD has increased with the global epidemic of obesity and type 2 diabetes mellitus. The pathophysiological hallmark of NAFLD is insulin resistance, associated with mediators of oxidative stress and inflammatory cytokines. Although simple steatosis by itself is generally benign, patients with histologically proven non-alcoholic steatohepatitis (NASH) can progress to cirrhosis. Hepatitis C (HCV) is another common cause of liver disease with some potential for progression to cirrhosis. Steatosis is present in almost 50% of patients infected by HCV. Hepatic steatosis in the setting of another liver disease (such as HCV) is associated liver disease progression. In particular, significant fibrosis is observed in patients with HCV whose liver biopsies show significant steatosis or superimposed NASH. This article reviews the host and viral factors potentially involved in the interaction between NAFLD and HCV. These factors include mediators of metabolic syndrome such as adipokines, inflammatory cytokines, factors associated with oxidative stress, lipid peroxidation products, as well as apoptosis and hepatic stellate cell activation with the resultant deposition of extracellular matrix. In addition to the mediators of metabolic syndrome (host factors), hepatic steatosis can be influenced by viral factors. The most important viral factor is HCV genotype 3, which has been independently associated with hepatic steatosis. Finally, superimposed NAFLD and visceral fat are associated with lower response rates to antiviral therapy in non-genotype 3 patients. Furthermore, viral clearance is associated with the resolution of hepatic steatosis in HCV genotype 3 but not other HCV genotypes. In these genotypes, hepatic steatosis and its impact on response to therapy are related to metabolic syndrome. Thus, the management of obesity and metabolic syndrome in patients with chronic hepatitis C may be important for reducing the risk of progression as well as improving the efficacy of antiviral therapy.
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PMID:Non-alcoholic fatty liver disease and hepatitis C infection. 1655 85

Accumulating evidence supports an association between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome, diabetes, and obesity. The epidemiology, pathogenesis, and approach to treatment of NAFLD follow the same trends as these other metabolic disorders, and insulin resistance is the key event linking NAFLD to these diseases. The impairment in fat and glucose metabolism that ensues once insulin resistance occurs leads to similar biochemical and clinical abnormalities in patients with NAFLD. Many recent studies investigating the cellular and genetic basis of these diseases have led to a better understanding of their pathogenesis and insight into treatment and management. The most effective treatment thus far is weight loss and the use of insulin-modulating pharmacologic agents. A few additional treatment strategies include the use of lipid-lowering, antioxidants or cytoprotective agents, but there is no single therapeutic approach that is effective for managing NAFLD. Future therapies may combine drugs that target specific pathways involved in NAFLD pathogenesis.
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PMID:The metabolic syndrome and nonalcoholic fatty liver disease. 1663 31

By far the most common dyslipoproteinema in patients with liver disease is hypertriglyceridemia with decreased HDL cholesterol occurring in fatty liver diseases. Since these latter frequently occur in patients with a metabolic syndrome, it must be assumed that lipid metabolism disorder is associated with a pronounced atherogenic effect. This means that--in contrast to cholestatic liver disease--treatment is almost always indicated. General therapeutic measures (weight reduction, optimization of blood sugar) are to the fore. As medication, metformin, fibrates and insulin sensitizers may be considered since, apart from improving glucose metabolism and hypertriglyceridemia, they also have a direct hepatic effect. It must, however, be noted that the available study data are not yet satisfactory, so that an individual decision must be made as to whether medical treatment of a lipid metabolism disorder makes good lipidological sense and is hepatologically justified.
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PMID:[Secondary dyslipoproteinema in liver disease]. 1666 79

The management of nonalcoholic fatty liver has been limited by a paucity of well-conducted studies that are of sufficient duration and quality to determine the outcome, which is best defined by liver biopsy. The mainstays, diet and physical activity plus behavioral modifications, are not always successful, particularly in the very obese. Although it is intuitive to expect that weight loss should diminish steatosis, only limited evidence exists that liver enzymes improve with reduction in body weight. The available pharmacologic therapy has focused on the two limbs of the pathogenetic basis for nonalcoholic steatohepatitis (NASH), insulin resistance and oxidative stress, but with quite limited success. Neither behavioral, nor dietary, nor drug therapy has been particularly effective either in obesity or NASH. In the severely obese, the fatty liver and its stages often have progressed to NASH or cirrhosis even before contemplating therapy. In the severely obese, the best therapeutic modality is bariatric surgery, which is safe and has been successful in producing a 61% weight loss overall. The result is improvement in diabetes mellitus, the metabolic syndrome, and presumably its sequelae. Early reports (and procedures) were attended with dramatic weight loss but markedly aggravated the inflammatory liver disease. In recent trials with more modest weight loss and less malnutrition, bariatric surgery reduced the fat, inflammation, and even the fibrosis in well-documented NASH. These promising procedures will undoubtedly increase and constitute the major therapeutic modality for those who are severely obese.
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PMID:Bariatric Surgery: A Promising Solution for Nonalcoholic Steatohepatitis in the Very Obese. 1667 25

Obesity and the metabolic syndrome have hepatic manifestations, including steatosis and progression of fibrosis. In individuals with chronic hepatitis C, obesity is associated with inflammation, insulin resistance, steatosis, progression of fibrosis, and nonresponse to treatment with interferon or peginterferon alpha and ribavirin. Patients with both hepatitis C and obesity-related nonalcoholic fatty liver disease are at greater risk for more advanced liver disease. We review the mechanisms by which obesity may be associated with decreased efficacy of interferon-based therapies in individuals with chronic hepatitis C and the therapeutic strategies that may increase the effectiveness of these therapies in obese individuals.
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PMID:Impact of obesity on treatment of chronic hepatitis C. 1672 27

In the past years, in Brazil and in developed countries, obesity has become a major public health problem. It was identified that besides DM2 and metabolic syndrome other clinical entities were associated with insulin resistance. In this review we describe some of these alterations emphasizing nonalcoholic fatty liver disease, but also including polycistic ovary disease, hyperuricemia, chronic renal failure, heart failure, cognitive decline and cancer.
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PMID:[Insulin resistance/hyperinsulinemia associated diseases not included in the metabolic syndrome]. 1676 2

Adiponectin is a fat cell-secreted hormone with antidiabetic and anti-inflammatory activities. The reduced adiponectin levels are associated with obesity-related metabolic syndrome. Replenishment of this hormone into animal models can improve insulin sensitivity, decrease blood glucose and lipid levels, and prevent the development of atherosclerosis and fatty liver injury. Despite these findings, the underlying molecular mechanisms remain largely unknown. Here, we have used affinity chromatography to purify the protein complexes that are associated with adiponectin in human serum. The nature of these adiponectin-binding proteins was analyzed by MS/MS. Eight proteins from the adiponectin-containing protein mixtures have been identified. Many of them, including thrombospondin-1 (TSP-1), histidine-rich glycoprotein, kininogen 1, and alpha 2 macroglobulin (alpha2M), are well-known glycoproteins involved in the regulation of inflammation, angiogenesis, and tissue remodeling. Coimmunoprecipitation and radioligand competitive-binding assays confirmed the direct interactions between adiponectin and alpha2M, or TSP-1. Moreover, these specific bindings were also detected in the serum samples derived from both healthy human subjects and patients with type 2 diabetes. In summary, our study demonstrated that, in the circulation, adiponectin forms protein complexes with other serum proteins. These proteins might serve as the physiological-binding partners of adiponectin and regulate its bioavailability and biological activities.
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PMID:Proteomic characterization of human serum proteins associated with the fat-derived hormone adiponectin. 1676 90

Visceral obesity and insulin resistance are typical clinical features of nonalcoholic steatohepatitis (NASH) characterized by zone 3-dominant hepatic steatosis with ballooned hepatocytes and Mallory bodies, zone 3 pericellular and perivenular fibrosis with or without bridging fibrosis, and lobular inflammatory cell infiltration. Indeed, 90% of NASH revealed to be complicated with visceral obesity, and two thirds of NASH patients fulfill the criteria of metabolic syndrome. Therefore, NASH could be regarded as the hepatic manifestation of metabolic syndrome, and a variety of life-style related diseases such as obesity, hypertension, hyperlipidemia and diabetes mellitus could be used for detecting
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PMID:[NASH and metabolic syndrome]. 1676 26

Nonalcoholic fatty liver disease is a common condition associated with metabolic syndrome. It is the most common cause of elevated liver enzymes in U.S. adults, and is diagnosed after ruling out other causes of steatosis (fatty infiltration of liver), particularly infectious hepatitis and alcohol abuse. Liver biopsy may be considered if greater diagnostic and prognostic certainty is desired, particularly in patients with diabetes, patients who are morbidly obese, and in patients with an aspartate transaminase to alanine transaminase ratio greater than one, because these patients are at risk of having more advanced disease. Weight loss is the primary treatment for obese patients with nonalcoholic fatty liver disease. Medications used to treat insulin resistance, hyperlipidemia, and obesity have been shown to improve transaminase levels, steatosis, and histologic findings. However, no treatments have been shown to affect patient-oriented outcomes.
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PMID:Nonalcoholic fatty liver disease. 1677 Sep 27

In the last 15 years evidence has been accumulating suggesting that hepatic steatosis may be the starting point for a progressive liver disease. Nonalcoholic steatosis (nonalcoholic fatty liver disease, NAFLD) is now considered a metabolic pathway to advanced liver disease, cirrhosis and hepatocellular carcinoma. Liver disease of other etiology, namely hepatitis C virus, may interact with NAFLD, although the underlying mechanism(s) have not been fully elucidated. Type 2 diabetes mellitus, obesity and dyslipidemia are the principal factors associated with NAFLD, which is now considered the hepatic expression of metabolic syndrome (MS). Several studies have dealt with the relationship of NAFLD and MS, the risk of liver disease associated with the classical features of MS, the importance of insulin resistance as the common soil of different diseases. We still need to clarify the mechanism(s) responsible for liver disease progression from pure fatty liver, to steatohepatitis and to cirrhosis, and the reason(s) why only a few NAFLD cases progress to terminal liver failure while others (the majority) will have a cardiovascular outcome. The epidemics of obesity and diabetes of Western countries is expected to produce a significant increase of metabolic liver disease in the next years. Prevention and intervention programs based on lifestyle are therefore mandatory to reduce the burden of metabolic liver disease.
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PMID:Nonalcoholic fatty liver disease and the metabolic syndrome. 1677 54


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