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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

Nonalcoholic fatty liver disease (NAFLD) is prevalent in people with the metabolic syndrome and type 2 diabetes. Evidence is now accumulating that NAFLD is associated with obesity and diabetes and may serve as a predictor of cardiovascular disease. Although at present, treatment of the individual risk factors pertinent to NAFLD is advocated, novel therapies are emerging that may target steatosis and/or inflammation, thus ameliorating the overall cardiovascular disease risk. Long-term outcome studies need to establish whether treatment of NAFLD (and in particular which therapy) will affect the long-term outcome.
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PMID:Nonalcoholic fatty liver disease and cardiovascular disease risk. 1754 35

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in Western industrialized countries, affecting 20-40% of the general population. Large population-based surveys in China, Japan, and Korea indicate that the prevalence of NAFLD is now 12% to 24% in population subgroups, depending on age, gender, ethnicity, and location (urban versus rural). There is strong evidence that the prevalence of NAFLD has increased recently in parallel with regional trends in obesity, type 2 diabetes, and metabolic syndrome; and that further increases are likely. The relationship between NAFLD, central obesity, diabetes, and metabolic syndrome is clearly evident in retrospective and prospective Asian studies, but the strength of association with these metabolic risk factors is only appreciated when regional definitions of anthropometry are used. Pathological definition of NAFLD, particularly its activity and the extent of liver fibrosis, requires histological examination, but liver biopsy is often not appropriate in this disorder for logistic reasons. An alternative set of operational definitions is proposed here. Clinicians need guidelines as how best to diagnose and manage NAFLD and its associated metabolic disorders in countries with scant healthcare resources. The Asia-Pacific Working Party (APWP) for NAFLD was convened to collate evidence and deliberate these issues. Draft proposals were presented and discussed at Asia-Pacific Digestive Week at Cebu, Philippines, in late November 2006, and are published separately in this issue of the Journal as an Executive Summary. The present document reviews the reasoning and evidence behind the APWP-NAFLD proposals for definition, assessment, and management of NAFLD in the Asia-Pacific region.
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PMID:Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines. 2235 48

Risk factors for development of non-alcoholic steatohepatitis include obesity, especially central adiposity, glucose intolerance or type 2 diabetes mellitus (T2DM), and dyslipidemia. Non-alcoholic fatty liver disease (NAFLD) is now considered a manifestation of metabolic syndrome. During the last two decades, NAFLD has become the most common chronic liver disease in North America and Europe, but until recently was thought to be uncommon (perhaps due to the lack of study) in Asia. Fatty liver can be identified on imaging modalities (ultrasonography, computed tomography scans, and magnetic resonance imaging) with high sensitivity, but steatohepatitis and fibrosis cannot be distinguished. Thus, an inherent drawback in studying the epidemiology of NAFLD is the lack of definitive laboratory tests, no uniform definition-with different studies using cut-off values of alcohol consumption from <20 g/week to 210 g/week, and case selections where biopsy was used for definition. In studies outside the region, the prevalence of NAFLD varies from 16% to 42% by imaging, and 15-39% of liver biopsies. The major risk factors for NAFLD, central obesity, T2DM, dyslipidemia, and metabolic syndrome, are now widely prevalent and are increasing geometrically in the Asia-Pacific region. It is therefore not surprising that NAFLD is common in this region. Estimates of current prevalence range from 5% to 30%, depending on the population studied. Central obesity, diabetes, and metabolic syndrome are the major risk factors. To date, however, data on the natural history and impact of NAFLD causing serious significant chronic liver disease are lacking and there is a need for prospective, cooperative studies.
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PMID:How common is non-alcoholic fatty liver disease in the Asia-Pacific region and are there local differences? 1756 29

Evidence-based management guidelines for non-alcoholic fatty liver disease (NAFLD) are lacking in the Asia-Pacific region or elsewhere. This review reports the results of a systematic literature search and expert opinions. The Asia-Pacific Working Party on NAFLD (APWP-NAFLD) has generated practical recommendations on management of NAFLD in this region. NAFLD should be suspected when there are metabolic risk factors and/or characteristic changes on hepatic ultrasonography. Diagnosis by ultrasonography, assessment of liver function and complications, exclusion of other liver diseases and screening for metabolic syndrome comprise initial assessment. Liver biopsy should be considered when there is diagnostic uncertainty, for patients at risk of advanced fibrosis, for those enrolled in clinical trials and at laparoscopy for another purpose. Lifestyle measures such as dietary restrictions and increased physical activity (aerobic exercise) should be encouraged, although the best management strategy to achieve this has yet to be defined. Complications of metabolic syndrome should be screened for regularly. Use of statins to treat hypercholesterolemia is safe and recommended; frequent alanine aminotransferase (ALT) monitoring is not required. Obese patients who do not respond to lifestyle measures should be referred to centers specializing in obesity management; consideration should be given to bariatric surgery or gastric ballooning. The role of pharmacotherapy remains investigational and is not recommended for routine clinical practice. Non-alcoholic fatty liver disease should be recognized as part of the metabolic syndrome and managed in a multidisciplinary approach that addresses liver disease in the context of risk factors for diabetes and premature cardiovascular disease. Lifestyle changes are the first line and mainstay of management.
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PMID:How should we manage patients with non-alcoholic fatty liver disease in 2007? 1756 32

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

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of liver-related morbidity and mortality. It can develop secondary to numerous causes but a great majority of NAFLD cases occur in patients who are obese or present with other components of metabolic syndrome (hypertension, dyslipidemia, diabetes). This is called primary NAFLD and insulin resistance plays a key role in its pathogenesis. Obesity is characterized by expanded adipose tissue, which is under a state of chronic inflammation. This disturbs the normal storage and endocrine functions of adipose tissue. In obesity, the secretome (adipokines, cytokines, free fatty acids and other lipid moieties) of fatty tissue is amplified, which through its autocrine, paracrine actions in fat tissue and systemic effects especially in the liver leads to an altered metabolic state with insulin resistance (IR). IR leads to hyperglycemia and reactive hyperinsulinemia, which stimulates lipid-accumulating processes and impairs hepatic lipid metabolism. IR enhances free fatty acid delivery to liver from the adipose tissue storage due to uninhibited lipolysis. These changes result in hepatic abnormal fat accumulation, which may initiate the hepatic IR and further aggravate the altered metabolic state of whole body. Hepatic steatosis can also be explained by the fact that there is enhanced dietary fat delivery and physical inactivity. IR and NAFLD are also seen in various lipodystrophic states in contrary to popular belief that these problems only occur due to excessive adiposity in obesity. Hence, altered physiology of adipose tissue is central to development of IR, metabolic syndrome and NAFLD.
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PMID:Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease. 1765 4

Nonalcoholic fatty liver disease (NAFLD) is now considered to be the most common liver disease in the United States and involves a spectrum of progressive histopathologic changes. Common risk factors associated with NAFLD include obesity, diabetes, and hyperlipidemia. Although most patients with NAFLD have simple hepatic steatosis, a significant number develop nonalcoholic steatohepatitis, which may progress to fibrosis, cirrhosis, or end-stage liver disease. There is increasing evidence that NAFLD is a common feature in patients with the cardiometabolic syndrome, a onstellation of metabolic, cardiovascular, renal, and inflammatory abnormalities in which insulin resistance is thought to play a key role in end-organ pathogenesis. NAFLD is usually diagnosed after abnormal liver chemistry results are found during routine laboratory testing. No therapy has been proven effective for treating NAFLD/nonalcoholic steatohepatitis. Expert opinion emphasizes the importance of exercise, weight loss in obese and overweight individuals, treatment of hyperlipidemia, and glucose control.
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PMID:Nonalcoholic steatohepatitis and the cardiometabolic syndrome. 1767 1

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 associated with diabetes, obesity and insulin resistance. The pathogenesis of NAFLD is complex, but modulation of the activities of transcription factors that regulate hepatic lipid and glucose homeostasis may be a key to treating NAFLD. An example of a key transcription factor regulating hepatic lipid metabolism is sterol regulatory element binding proteins (SREBPs), and in this review we present evidence supporting a key role for SREBPs in NAFLD. Currently, the only effective treatment for NAFLD is caloric restriction and peroxisome proliferator activated receptor (PPAR-gamma) agonists. We suggest that further studies are urgently needed to evaluate modulation of SREBP activity as a potential new treatment for NAFLD.
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PMID:Modulation of sterol regulatory element binding proteins (SREBPs) as potential treatments for non-alcoholic fatty liver disease (NAFLD). 1782 87


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