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 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Nonalcoholic fatty liver disease (NAFLD) has been associated with the insulin-resistance syndrome, at present defined as the metabolic syndrome, whose limits were recently set. We assessed the prevalence of the metabolic syndrome in 304 consecutive NAFLD patients without overt diabetes, on the basis of 3 or more criteria out of 5 defined by the U.S. National Institutes of Health (waist circumference, glucose, high-density lipoprotein [HDL]-cholesterol, triglycerides, and arterial pressure). The prevalence of the metabolic syndrome increased with increasing body mass index, from 18% in normal-weight subjects to 67% in obesity. Insulin resistance (Homeostasis Model Assessment method) was significantly associated with the metabolic syndrome (odds ratio [OR], 2.5; 95% CI, 1.5-4.2; P <.001). Liver biopsy was available in 163 cases (54%). A total of 120 patients (73.6%) were classified as having nonalcoholic steatohepatitis (NASH); 88% of them had a metabolic syndrome (vs. 53% of patients with pure fatty liver; P <.0001). Logistic regression analysis confirmed that the presence of metabolic syndrome carried a high risk of NASH among NAFLD subjects (OR, 3.2; 95% CI, 1.2-8.9; P =.026) after correction for sex, age, and body mass. In particular, the syndrome was associated with a high risk of severe fibrosis (OR, 3.5; 95% CI, 1.1-11.2; P =.032). In conclusion, the presence of multiple metabolic disorders is associated with a potentially progressive, severe liver disease. The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension, and ultimately the metabolic syndrome puts a very large population at risk of forthcoming liver failure in the next decades.
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PMID:Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. 1266 87

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

Nonalcoholic fatty liver disease (NAFLD) is a well recognised form of chronic liver disease that has recently gained greater recognition. Originally described in the late 1950s, NAFLD is currently considered the leading cause of abnormal liver enzyme levels in the US, closely paralleling the increase in obesity and diabetes mellitus. NAFLD has a worldwide distribution, affecting both adults and children, and typically is seen in association with obesity, diabetes, hypertension and hypertriglyceridaemia. Most patients are asymptomatic and usually present with mild elevations in aminotransferases. The natural history of NAFLD is not clearly defined but progression to cirrhosis and end-stage liver disease is well recognised in some patients. The accumulation of hepatic steatosis is thought to occur initially, primarily through hepatic and peripheral insulin resistance, which leads to altered glucose and free fatty acid metabolism. The progression from simple fatty liver to more severe forms of NAFLD (nonalcoholic steatohepatitis and cirrhosis) is much less clear but evidence suggests that oxidative stress may preferentially enhance proinflammatory cytokines, which leads to cellular adaptations and dysfunction followed by development of inflammation, necrosis and fibrosis. Therapeutic modalities remain limited and are largely focused on correcting the underlying insulin resistance or reducing oxidative stress. However, at the present time, there are several limitations to the current potential therapies, mainly because of the lack of large-scale, prospective, randomised studies, as well as clearly defined histological endpoints. Ultimately, the future for potential therapeutic modalities to treat this disease are quite promising, but further research is needed to clearly demonstrate which therapy or therapies will be effective at eliminating fatty liver disease and its potential complications.
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PMID:Advances in the understanding and treatment of nonalcoholic fatty liver disease. 1460 46

Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as a common liver disorder that represents the hepatic manifestation of the metabolic syndrome, a variably defined aggregate of disorders related to obesity, insulin resistance, type II diabetes, hypertension and hyperlipidemia. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury that carries a risk for progressive fibrosis, cirrhosis, and end-stage liver disease. Hepatocellular carcinoma (HCC) is a documented complication in an as yet unknown percentage of cases of NASH cirrhosis. The diagnosis of nonalcoholic steatohepatitis requires histopathologic evaluation because the lesions of parenchymal injury and fibrosis cannot be detected by imaging studies or laboratory tests. This article will briefly discuss prevalence studies and the pathophysiology of NAFLD and focus on current discussions related to the specific lesions in the pathology of NASH, including the challenges of pediatric NASH and NASH-related cirrhosis.
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PMID:Nonalcoholic steatohepatitis. 1508 83

Non-alcoholic steatohepatitis (NASH) can vary from mild hepatic inflammation and steatosis to cirrhosis, and is most frequently associated with obesity, Type 2 diabetes mellitus, hypertension, and the female gender. The prevalence of fatty liver and NASH in the general population is 20% and 3%, respectively. In Western countries, 15-20% of the population is obese and 74-90% of them exhibit fatty changes in liver biopsies. We assessed the prevalence of NASH in morbidly obese patients and evaluated serum TGF-beta1 concentrations in different stages of liver fibrosis. Thirty-five obese patients were evaluated, nine male and 26 female. Their mean body mass index (BMI) was 43.62 +/- 7.92 kg/m2. Liver biopsies were evaluated by light microscopy; graded and staged according to Brunt's system. Serum obtained from patients was used to detect TGF-beta1 concentrations by an ELISA method. Serum alanine transaminase (ALT) levels were elevated in four of the patients and the mean level was 49.98 +/- 94.7 (8-65 IU/L). NASH was diagnosed in 32 (91%) of the biopsies, and the most common pattern seen was mixed, predominantly macrovesicular steatosis. Some degree of fibrosis was seen in 34 (97%) of the biopsies and 22 (63%) were at stage 2 (range 1-3). Serum concentrations of TGF-beta1 had no relationship with the stages of fibrosis. In conclusion, NASH and fibrosis are common in our obese patients, as observed in other studies. TGF-beta1 may play a key role in liver fibrogenesis.
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PMID:Obesity-related non-alcoholic steatohepatitis and TGF-beta1 serum levels in relation to morbid obesity. 1511 94

Nonalcoholic fatty liver disease (NAFLD), already the most common form of liver disease in the United States, can be expected to increase in prevalence and severity in parallel with national epidemics of obesity and type 2 diabetes. NAFLD is frequently associated with insulin resistance. While insulin resistance, and thereby hyperinsulinemia, are, in large part, metabolic consequences of obesity, the basis of diversity in severity and progression of inflammation and fibrosis is not known. Increased susceptibility to oxidative stress is likely to play a role. Several patient characteristics have been associated with more severe histological findings in patients with NAFLD, including type 2 diabetes, hypertension, age over 40 years, and higher transaminases. Liver biopsy is, however, required to accurately grade and stage NAFLD histologically. Although the natural history of NAFLD is relatively poorly defined, NAFLD is increasingly recognized as an important cause of decompensated liver disease. Weight reduction and improved insulin sensitivity are associated with improved biochemical and histological parameters of NAFLD. There are, however, no proven safe and efficacious pharmacological treatments for NAFLD.
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PMID:Nonalcoholic fatty liver disease: a review of current understanding and future impact. 1562 47

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20

Nonalcoholic fatty liver disease (NAFLD) refers to a wide picture of liver damage, ranging from steatosis to steatohepatitis, fibrosis and cirrhosis. The epidemiological studies demonstrated an association of NAFLD with obesity, type 2 diabetes and hyperlipidemia. Under this light the metabolic syndrome (MS), including NAFLD, obesity, central fat distribution, diabetes, dyslipidemia, hypertension and atherosclerotic cardiovascular disease (CVD) can be considered the link to explain the presence of vascular diseases in patients with NAFLD. In NHANES III, the authors demonstrated that the presence of MS was associated with increased risk of myocardial infarction, stroke or both. In a prospective study on 1209 Finnish middle-aged men without CVD or diabetes at baseline, Lakka showed that MS per se is associated with an increased risk of CVD and all-cause mortality. Finally the Atherosclerosis Risk in Communities (ARIC) confirmed that subjects with MS were 2 times more likely to have prevalent coronary heart disease. From a pathophysiological point of view, growing evidences implicate the oxidative stress as the unifying mechanism for many CVD risk factors. Under this light there is emerging evidence suggesting that there is a significant increase in vascular oxidative stress in patients with MS, with the presence of endothelial dysfunction in the early stage of the syndrome. Indeed, the inflammation process evidentiated in these patients is initiated at the endothelial level, stressing the key role of this active and dynamic tissue in the pathophysiological pathways. Under this light the endothelium can be considered as the last effector of a multi-syndrome and the main target of all the future studies focused on the underlying mechamisms of this complex network. Because of the potential serious public health impact, the comprehension of these patophysiological pathways will be crucial to design new preventive measures and therapeutic strategies.
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PMID:Hepatic steatosis and vascular disease. 1623 88

Nonalcoholic fatty liver disease (NAFLD) is a diagnostic consideration among patients with asymptomatic elevated aminotransaminases, patients with radiologic findings of hepatic fatty infiltration, or occasionally in the patient with "cryptogenic" cirrhosis. The diagnosis of NAFLD requires evidence of fatty infiltration of the liver in the absence of excessive alcohol ingestion. Clinical evaluation should examine for metabolic risk factors (central obesity, glucose intolerance, hypertension, hypertriglyceridemia, and low HDL cholesterol), which are suggestive but not specific for the diagnosis of NAFLD. Secondary causes of NAFLD, such as medications and intestinal bypass surgery, should be excluded as management of these conditions may differ. Confirmation of hepatic steatosis can usually be done by imaging studies, although occasionally liver biopsy is required. Among suspected NAFLD patients with chronically elevated aminotransaminases, clinical evaluation and serological testing should be performed to exclude other causes of chronic liver disease. Liver biopsy is required to stage fibrosis and distinguish between nonalcoholic steatohepatitis and steatosis. This is valuable for providing prognosis, excluding other liver disease, monitoring response to therapy or evaluating disease progression over time. Clinical features, particularly diabetes, obesity, and older age, can aid in stratifying patients at risk for advanced fibrosis but are not sufficiently accurate to replace liver biopsy.
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PMID:Diagnostic evaluation of nonalcoholic fatty liver disease. 1654 Jul 65


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