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Nonalcoholic fatty liver disease (NAFL) has been recognized only in the past 20 years. Autopsy studies indicate it is remarkably common, especially among obese persons and patients with type 2 diabetes. Although fatty liver alone is usually benign, an identifiable subset of patients may be at risk of progression to cirrhosis and liver failure. The role of liver biopsy is controversial. No specific, effective therapy as yet exists, although management of weight, lipid levels, and glucose levels is recommended.
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PMID:The spectrum of nonalcoholic fatty liver disease: from steatosis to nonalcoholic steatohepatitis. 1068 Feb 76

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.
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PMID:Non-alcoholic steatohepatitis: association with obesity and insulin resistance, and influence of weight loss. 1080 23

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 a chronic liver disease that occurs in nondrinkers but which cannot be distinguished from alcohol-induced liver disease histologically. There are no diagnostic blood tests for NAFLD but the disease is associated with several insulin-resistant states, including obesity, type 2 diabetes mellitus and dyslipidemia. Most of the liver-related morbidity and mortality that accompany NAFLD occur in patients who develop cirrhosis. The latter is most likely to occur in individuals who have progressed from simple steatosis (fatty liver) to steatohepatitis, a chronic inflammatory liver lesion. The mechanisms that promote the transition from steatosis to nonalcoholic steatohepatitis appear to involve multiple cellular adaptations to the oxidative stress that occurs when fatty acid metabolism is deranged during insulin resistance. A better understanding of these mechanisms is desired to target treatments to prevent and/or reverse nonalcoholic steatohepatitis, thereby aborting the evolution of cirrhosis.
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PMID:Fat and the liver--a molecular overview. 1194 31

Nonalcoholic fatty liver disease (NAFLD) encompasses a broad clinicopathologic spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may advance to cirrhosis and end-stage liver disease. Steatosis alone does not appear to be progressive. The prevalence of NAFLD averages 20% and that of NASH, 2% to 3%, making these conditions the most common liver diseases in the United States. NAFLD is associated with insulin resistance, which may be evident clinically with obesity, type 2 diabetes mellitus, and hypertriglyceridemia. The pathogenesis of NAFLD consists of hepatic fat accumulation and oxidative stress with formation of free radicals. The clinical diagnosis is based on the presence of the insulin resistance syndrome and exclusion of alcohol abuse as well as viral, autoimmune, genetic, and drug-induced liver diseases. Liver biopsy is essential for diagnosis but may not be necessary for clinical management. Treatment is aimed at correcting the risk factors for NAFLD and using potentially hepatoprotective agents. Ursodeoxycholic acid and betaine appear particularly promising in early trials.
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PMID:Nonalcoholic fatty liver disease. 1212 75

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

Non-alcoholic steatohepatitis (NASH) is a disease of emerging identity and importance. It is frequently associated with obesity, especially visceral fat, and is intimately related to fatty liver and markers of the insulin resistance syndrome. Both the prevalence and the severity of liver steatosis are related to body mass index, waist circumference, hyperinsulinaemia, hypertriglyceridaemia and impaired glucose tolerance or type 2 diabetes. The identification of obese patients who may progress from steatosis to NASH and from NASH to fibrosis/cirrhosis is an important clinical challenge. Substantial weight loss is accompanied by a marked attenuation of insulin resistance and related metabolic syndrome and, concomitantly, by a remarkable regression of liver steatosis in most patients, although increased inflammation may be detected in some subjects. Thus, NASH may be considered as another disease of affluence, as is the insulin resistance syndrome, and perhaps being part of it, especially in obese patients.
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PMID:Obesity and liver disease. 1246 16

Non-alcoholic steatohepatitis (NASH), is a critical link in the chain of metabolic fatty liver disorders that spans steatosis to cryptogenic cirrhosis. It is the hepatic manifestation of the insulin resistance (or metabolic) syndrome, and provides a clue to understanding fibrotic progression of other chronic liver diseases, particularly hepatitis C. Non-alcoholic steatohepatitis is often the first clinical indication of insulin resistance, with its complications of high blood pressure, coronary heart disease and type 2 diabetes. Among those with risk factors, NASH is common: present in at least 20% of obese adults or children with or without type 2 diabetes, and at least 5% of those overweight. With emerging urbanization, increasing affluence and behavioral changes of physical inactivity and high fat/energy-excessive diet, type 2 diabetes has become common in Asia and the western Pacific rim. The rates range from 7-40%, which in countries like Japan represents a 3-20-fold increase (depending on age) over the last 20 years. The increase is associated with central adiposity, insulin resistance, hepatic steatosis and NASH. After cancer, cirrhosis from NASH is now the second most common age-related cause of death in type 2 diabetes. Reversing these trends must become a public health priority; the first awakenings were evident in Taiwan at the time of this meeting. In order to stimulate clinicians to think more about the importance of metabolic liver disease for development of cirrhosis, this review will cover clinical and laboratory features, natural history and an approach to diagnosis and management of NASH. Some emerging concepts on pathogenesis will be mentioned briefly, but the emphasis will be on the potency of lifestyle adjustments (physical activity and diet) to prevent or reverse fatty liver disorders.
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PMID:Non-alcoholic steatohepatitis: what is it, and why is it important in the Asia-Pacific region? 1254 95

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

Cryptogenic cirrhosis is a common cause of liver-related morbidity and mortality in the United States. Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of cryptogenic cirrhosis. However, the diagnosis of cirrhosis in patients with NAFLD appears to be delayed compared with those with other chronic liver diseases and thus carries a higher mortality rate. This delay in diagnosis is illustrated in our case of a 53-year-old man who presented with hepatic hydrothorax and ascites, whose workup revealed cirrhosis due to NAFLD. Although a diagnosis of presumed NAFLD can be made noninvasively, a definitive diagnosis requires a liver biopsy specimen. A biopsy specimen is also important for detecting histologically advanced disease, which may be clinically silent and undetected by aminotransferases or diagnostic imaging. Although there are no proven treatments, recommendations for patients with NAFLD include avoidance of hepatotoxins and aggressive management of associated conditions, such as hypertriglyceridemia and type 2 diabetes mellitus.
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PMID:Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. 1450 12


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