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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcoholic steatohepatitis (NASH) may present with increased hepatic fibrosis progressing to end-stage liver disease. No factors that determine increasing fibrosis and histologically advanced disease have been recognized, thus, liver biopsy is recommended in all patients for diagnosis and prognosis. Our aim was to identify independent predictors of severe hepatic fibrosis in patients with NASH. One hundred and forty-four patients were studied. All patients underwent liver biopsy. Clinical and biochemical variables were examined with univariate and multivariate analysis. Thirty-seven (26%) patients had no abnormal fibrosis, 53 (37%) had mild fibrosis, 15 (10%) had moderate fibrosis, 14 (10%) had bridging fibrosis, and 25 (17%) had cirrhosis. In multivariate analysis, older age (P =. 001), obesity (P =.002), diabetes mellitus (P =.009), and aspartate transaminase/alanine transaminase (AST/ALT) ratio greater than 1 (P =.03) were significant predictors of severe liver fibrosis (bridging/cirrhosis). Body mass index (P =.003) was the only independent predictor of the degree of fat infiltration. Increased transferrin saturation correlated positively with the severity of fibrosis (P =.02) in univariate analysis, and there was a trend for more female patients among those with more advanced fibrosis (P =. 09). However, iron studies or gender were not significant when controlled for age, obesity, diabetes, and AST/ALT ratio. In conclusion, older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis. This is the subgroup of patients with NASH who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.
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PMID:Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. 1057 11

Obesity is associated with a number of metabolic and haemodynamic risk factors for cardiovascular disease and type 2 diabetes mellitus. This risk depends on a complex of metabolic and haemodynamic consequences of (visceral) fat accumulation, which probably results from the continuous delivery of fatty acids to the liver via the portal vein. Hypertriglyceridaemia, hyperinsulinaemia, hypertension, insulin resistance and increased hepatic glucose production are all independent risk factors for atherosclerosis. Their combination increases the risk of cardiovascular disease considerably. Triglyceride storage in hepatocytes is another consequence of increased fatty acid supply to the liver. Until recently, hepatic steatosis was considered a harmless condition secondary to obesity or alcoholism. However, it may lead to non-alcoholic hepatic steatosis, which predisposes to liver fibrosis and even cirrhosis.
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PMID:[Abdominal obesity: metabolic complications and consequences for the liver]. 1160 19

Nonalcoholic steatohepatitis (NASH) may progress to liver fibrosis and cirrhosis. Mechanisms directly involved in the development of fibrosis have been poorly investigated. Because connective tissue growth factor (CTGF) is an intermediate key molecule involved in the pathogenesis of fibrosing chronic liver diseases and is potentially induced by hyperglycemia, the aims of this study were to (1) study the expression of CTGF in vivo both in human liver biopsy specimens of patients with NASH and in an experimental model of obesity and type II diabetes (Zucker rats); and (2) analyze the effects of hyperglycemia and insulin in vitro on hepatic stellate cells. In vivo, CTGF overexpression was observed in the liver tissue of all of the 16 patients with NASH. CTGF immunostaining was mild in 7 cases (44%) and moderate or strong in 9 cases (56%). Staining was mainly detected in the liver extracellular matrix in parallel with the amount of liver fibrosis. Liver from fa/fa rats also showed CTGF overexpression by comparison with Fa/fa rats both at the messenger RNA (mRNA) level (3-fold increase) and protein level. In vitro, both CTGF mRNA and protein were significantly increased when hepatic stellate cells were incubated with either glucose or insulin. A slight increase in type I procollagen mRNA level was also observed in hepatic stellate cells incubated with glucose. In conclusion, this study suggests that hyperglycemia and insulin are key-factors in the progression of fibrosis in patients with NASH through the up-regulation of CTGF.
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PMID:High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. 1158 70

PPAR-gamma belongs to the nuclear hormone receptor superfamily and its ligands include antidiabetic drugs of the thiazolidindione class, and endogenous molecules, including eicosanoids and fatty acids. PPAR-gamma is involved in the pathophysiology of obesity and type II diabetes. More recently, accumulating evidence suggests its role in atherosclerosis, inflammation and cancer. Recent data obtained in cellular models of liver fibrosis indicate that PPAR-gamma activation results in the inhibition of the processes leading to the development of liver fibrosis. These studies identify potential novel therapeutic strategies for the treatment of liver fibrosis.
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PMID:[Thiazolidinediones and PPARgamma system in repair of liver damage]. 1185 Oct 3

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 (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

The purpose of this study was to clarify the clinicopathological features of nonalcoholic steatohepatitis (NASH) and identify risk factors for severe hepatic fibrosis. MATERIALS AND METHODS: Eighty-one patients with biopsy-proven NASH were studied. In all patients, the diagnosis of NASH was established on the basis of following criteria: (1) the presence of steatosis, lobular inflammation, and ballooning degeneration on liver biopsy, (2) intake of less than 20 g of ethanol per week, and (3) appropriate exclusion of other liver diseases. RESULTS: The median age was 54 years (range: 21-82 years) and 41 patients were women (51%). Obesity was present in 58 patients (72%), while 25 patients (31%) had diabetes mellitus and 33 patients (41%) had hyperlipidemia. Histologically, 58 patients (72%) had trivial to moderate fibrosis, 6 patients (7%) had bridging fibrosis, and 17 patients (21%) had established cirrhosis. Multiple logistic regression analysis assessed clinical, laboratory and histological factors showed that the risk factors for fibrosis were a low platelet count (P=0.0016), a high AST/ALT ratio (P=0.0229), and the presence of Mallory bodies (P=0.0209). To exclude factors that were a consequence of liver cirrhosis, variables included in the multiple logistic analysis were age, gender, diabetes, obesity, and hyperlipidemia. This showed that older age (P=0.0037) and the absence of hyperlipidemia (P=0.0150) were risk factors for fibrosis. CONCLUSIONS: We found that a low platelet count, a high AST/ALT ratio, and the presence of Mallory bodies were significant predictors of severe liver fibrosis.
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PMID:Nonalcoholic steatohepatitis: risk factors for liver fibrosis. 1247 42

Non-alcoholic fatty liver disease (NAFLD) is one of the most common hepatic disorders in the Western world. Non-alcoholic steatohepatitis (NASH) may occur in a subset of NAFLD patients and is an increasingly recognised clinicopathologial hepatic disorder. NASH may have significant impact on the healthcare system as it is associated with the metabolic syndrome comprising insulin resistance, obesity, hypertension, and type 2 diabetes mellitus. NASH can progress to liver fibrosis, cirrhosis and chronic hepatic failure and eventually to the need for a liver transplantation. The present review deals with the epidemiological features of NASH, describes a two-step pathogenesis with hepatic lipid accumulation (NAFLD) followed by the development of steatohepatitis (NASH). A strategy for establishing a diagnosis of NASH is presented including the indication for liver biopsy. The treatment of NASH may comprise different modalities from diet, weight loss, and exercise to pharmacological treatment to improve insulin resistance and drugs with antioxidant effects.
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PMID:[Nonalcoholic steatohepatitis--a "new" hepatic disease]. 1267 84

Non-alcoholic steatohepatitis (NASH) may develop in a subset of patients with non-alcoholic fatty liver disease (NAFLD). NASH is strongly associated to the metabolic syndrome with insulin resistance and obesity. NASH can progress to liver fibrosis, cirrhosis and chronic hepatic failure and eventual need for a liver transplantation. Three case stories are presented with characteristic clinical and histopathological changes.
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PMID:[Nonalcoholic steatohepatitis. Three case reports]. 1267 86

It is increasingly recognized that host factors can modulate the fibrogenic response in patients with chronic hepatitis C. Obesity, because of its prevalence, and diabetes, which seems to occur more frequently in patients infected by the hepatitis C virus (HCV), are often present in patients with chronic hepatitis C. Both conditions result in fatty liver, which in turn is associated with more severe liver damage, especially fibrosis or inflammation. Steatosis can either originate from associated metabolic alterations (insulin resistance resulting in metabolic steatosis) or from a direct cytopathic effect of the virus (genotype 3, resulting in viral steatosis). Metabolic steatosis seems to be a factor in resistance to antiviral therapy, whereas viral steatosis is reduced in sustained responders. Whether metabolic steatosis has a direct role in liver fibrosis progression or is only a surrogate marker of an underlying defect triggering fibrogenesis, such as insulin resistance, is a subject of debate. High serum glucose levels and diabetes have a strong and independent profibrogenic impact. Exciting new data are expanding our understanding of the mechanisms of steatogenesis in HCV infection and providing potential links between insulin resistance or hyperglycemic states and liver fibrogenesis.
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PMID:Fat, diabetes, and liver injury in chronic hepatitis C. 1472 Apr 50


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