乌鲁木齐地区脂肪肝发病率及非酒精性脂肪肝与代谢综合征的关系

目的了解乌鲁木齐地区机关汉族成人非酒精性脂肪肝及酒精性脂肪肝的流行状况,并分析非酒精性脂肪肝与代谢综合征的关系。方法对1037例体检者的问卷调查、体格检查、生化、肝脏超声检查等相关资料进行分析。结果乌鲁木齐地区成人脂肪肝检出278例,脂肪肝发生率为检出率为26.8%,非酒精性脂肪肝188例,占18.1%,其中男性161例,女性27例;酒精性脂肪肝90例,占8.7%,其中男性84例,女性6例,男性NAFLD高于女性。NAFLD患者合并MS共计115例,伴有率为61.2%。结论乌鲁木齐地区机关汉族成人脂肪肝（NAFLD及AFLD）患病率远高于国内以及世界范围平均患病率,体现了低龄化趋势及中年年龄段的患病高峰特点;年龄、BMI、WHR、TG以及FPG为NAFLD的相关危险因素,NAFLD可以作为MS组成成分之一。     

非酒精性脂肪性肝病与肝移植

随着生活水平的提高,非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)在人群中的发病率越来越高.非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)是NAFLD的最严重类型,在发达国家已成为临床上最常见的慢性肝病类型.     

非酒精性脂肪性肝病与肝硬化

非酒精性脂肪性肝病（Nonalcoholic fatty liver disease, NAFLD）发病与胰岛素抵抗（Insulin resistance, IR） 和遗传易感性密切相关,病理学改变与酒精性肝病（Alcoholic liver disease, ALD）相似,但无过量饮酒史^[1]。在此要强调NAFL与NASH的不同,NAFL是指病理活检显示肝脏脂肪变性,但是不具有肝纤维化或气球样变性的肝细胞损伤。NASH指在肝脏脂肪变基础上出现气球样肝细胞损伤伴或不伴肝纤维化^[2],NASH发生肝纤维化、肝硬化、肝细胞癌风险明显增高,而NAFL则很低^[2],NASH是NAFL发生肝硬化的必经阶段^[3]。     

Nonalcoholic fatty liver disease and cardiovascular disease

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are two diseases that are common in the general population. To date, many studies have been conducted and demonstrate a direct link between NAFLD and CVD, but the exact mechanisms for this complex relationship are not well established. A systematic search of the PubMed database revealed that several common mechanisms are involved in many of the local and systemic manifestations of NAFLD and lead to an increased cardiovascular risk. The possible mechanisms linking NAFLD and CVD include inflammation, oxidative stress, insulin resistance, ectopic adipose tissue distribution, dyslipidemia, endothelial dysfunction, and adiponectin, among others. The clinical implication is that patients with NAFLD are at an increased risk of CVD and should undergo periodic cardiovascular risk assessment.     

Nonalcoholic fatty liver disease and vascular disease:State-of-the-art

Nonalcoholic fatty liver disease(NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis(NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis(increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific lifestyle modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.     

Nonalcoholic fatty liver disease and aging: Epidemiology to management

Nonalcoholic fatty liver disease(NAFLD) is common in the elderly, in whom it carries a more substantial burden of hepatic(nonalcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma) and extra-hepatic manifestations and complications(cardiovascular disease, extrahepatic neoplasms) than in younger age groups. Therefore, proper identification and management of this condition is a major task for clinical geriatricians and geriatric hepatologists. In this paper, the epidemiology and pathophysiology of this condition are reviewed, and a full discussion of the link between NAFLD and the aspects that are peculiar to elderly individuals is provided; these aspects include frailty, multimorbidity, polypharmacy and dementia. The proper treatment strategy will have to consider the peculiarities of geriatric patients, so a multidisciplinary approach is mandatory. Non-pharmacological treatment(diet and physical exercise) has to be tailored individually considering the physical limitations of most elderly people and the need for an adequate caloric supply. Similarly, the choice of drug treatment must carefully balance the benefits and risks in terms of adverse events and pharmacological interactions in the common context of both multiple health conditions and polypharmacy. In conclusion, further epidemiological and pathophysiological insight is warranted. More accurate understanding of the molecular mechanisms of geriatric NAFLD will help in identifying the most appropriate diagnostic and therapeutic approach for individual elderly patients.     

Nonalcoholic fatty liver disease and atherosclerosis

Atherosclerosis is a complex inflammatory disease comprising multiple plaque phenotypes. The development of advanced atheromatous plaques with necrotic core represents the result of the invasion of lipid pools by macrophages. The release of activated proteolytic enzymes degrades the surrounding tissue and contributes to the formation of vulnerable plaque. Thinning of the fibrous cap and necrotic core expansion are considered to be critical for the progression toward plaque rupture and acute thrombosis. The pathogenic mechanisms leading the progression of atherosclerotic lesions are various and involve endothelial cells, inflammatory cells, and platelets. Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of diseases ranging from simple fatty liver to nonalcoholic steatohepatitis (NASH) and may progress to cirrhosis and hepatocellular carcinoma. The prevalence of this pathology is quite high in the general population and is one of the most important causes of liver-related morbidity and mortality in children. NAFLD is considered the hepatic feature of the metabolic syndrome and this has stimulated interest in its possible role in the atherosclerosis development. Clinical observations indicated that NAFLD might be an independent risk factor for coronary artery disease. Moreover, NASH may increase atherosclerotic and cardiovascular risks by local overexpression of inflammatory mediators, endothelial damage, and regulators of blood pressure. NASH development is correlated with hepatic progenitor cell activation and the release of proatherogenic adipokines. These aspects suggest the necessity for an early therapeutic intervention in NASH patients, not only for ameliorating the liver injury, but also for improving the systemic proatherogenic state.     

Nonalcoholic fatty liver disease: Evolving paradigms

In the last years new evidence has accumulated on nonalcoholic fatty liver disease(NAFLD)challenging the paradigms that had been holding the scene over the previous 30 years.NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases.Conversely,focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach.NAFLD,which can be diagnosed with either non-invasive strategies or through liver biopsy,is a pathogenically complex and clinically heterogeneous disease.The existence of metabolic as opposed to genetic-associated disease,notably includinglean NAFLDhas recently been recognized.Moreover,NAFLD is a systemic condition,featuring metabolic,cardiovascular and(hepatic/extrahepatic)cancer risk.Among the clinico-laboratory features of NAFLD we discuss hyperuricemia,insulin resistance,atherosclerosis,gallstones,psoriasis and selected endocrine derangements.NAFLD is a precursor of type 2 diabetes(T2D)and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD.Finally,lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed.In conclusion,this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD,a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations.It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies,intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible.     

儿童非酒精性脂肪性肝病研究进展

非酒精性脂肪性肝病（NAFLD）是导致儿童及青少年肝病的最常见原因。近年来,由于肥胖症的发病率逐年升高,NAFLD的患病率也明显增加。对于非酒精性脂肪性肝炎（NASH）的确诊及分级依赖于组织活检。一些非创伤性的检测指标及影像技术的发展有助于在NAFLD高风险人群中进行大范围筛查。在儿童患者中存在两种组织类型不同的NASH,其临床特征及人群特征也有差异。至今并未有儿童NAFLD的最佳治疗方案,但研究人员认为生活方式干预如饮食控制或锻炼具有一定作用。维生素E和二甲双胍对儿童NAFLD的治疗作用正处于临床研究之中。     

Nonalcoholic fatty liver disease in children

Nonalcoholic fatty liver disease (NAFLD) is likely to reach epidemic proportions in children worldwide in the next decade. NAFLD may be the hepatic aspect of the metabolic syndrome in adults and children. The entire range of liver involvement characterizing NAFLD can occur in children: hepatic macrovesicular steatosis without inflammation, steatosis with inflammation or fibrosis, and cirrhosis. NAFLD may be more severe in children from certain ethnic groups or in association with metabolic disorders characterized by abnormalities in insulin receptor structure and function. Treatment strategies focus on modifying risk factors because specific drug treatments are lacking. Overweight/obesity should be identified as early as possible. Comprehensive clinical management to normalize weight should be instituted immediately to avoid hepatic and nonhepatic complications.     

Nonalcoholic fatty liver disease: Diagnostic biomarkers

Nonalcoholic fatty liver disease is a common medical condition worldwide and its prevalence has increased notably in the past few years due to the increases in prevalence of obesity and metabolic syndrome. However, diagnosis of this disease is still a matter of debate because of disease variations and pathophysiologic alterations. Specific single markers have gained con-siderable attention recently, among them markers related to hepatic pathophysiology, inflammation, adipocytokines and so forth. But, it seems that no single marker is sufficient for diagnosis and staging of the disease, and applying a panel including different types of tests may be more useful.     

Nonalcoholic fatty liver disease: from clinical recognition to treatment

Nonalcoholic fatty liver disease (NAFLD) is probably the most common spectrum of metabolic liver disease in the world, encompassing simple steatosis to steatohepatitis, advanced fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD affects a significant part of the general population worldwide. The existing correlation between obesity and NAFLD in combination with the increase in the frequency of obesity in the developed world implies that the incidence and severity of NAFLD will increase in the near future. Newer data support the idea that NAFLD constitutes the more important cause of cryptogenic cirrhosis of the liver and a ground for the development of hepatocellular carcinoma. Liver biopsy remains the most specific and sensitive method to differentiate NAFLD, providing important information on the long-term prognosis of the patients. The ‘two hit’ hypothesis constitutes the currently prevailing theory for the development of NAFLD and nonalcoholic steatohepatitis. The first ‘hit’ is purported to be the increase of free fatty acids in hepatocytes, which results in a decrease of β-oxidation. The second step includes all mechanisms contributing to the development of necroinflammation and fibrosis. Currently, an effective treatment for patients with NAFLD does not exist. Improvement in liver histology remains the primary goal of any therapeutic approach in patients with NAFLD. Viewing NAFLD in the frame of the metabolic syndrome opens the possibility that both the onset of the disease and disease progression could be prevented by changes in lifestyle. Physical exercise and a low calorie diet in combination with the gradual loss of body weight represent the cornerstone for the management of NAFLD patients.     

Nonalcoholic fatty liver disease: from pathogenesis to patient care

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. It encompasses a wide spectrum of liver lesions, from pure steatosis to end-stage liver disease with cirrhosis and hepatocellular carcinoma. Nonalcoholic steatohepatitis corresponds only to one stage of NAFLD. As NAFLD can be considered a liver manifestation of the metabolic syndrome, its prevalence is high in obese people and in patients who have type 2 diabetes-insulin resistance is one of the key elements of the pathogenesis of NAFLD. This disease is often asymptomatic in the absence of decompensated cirrhosis, but should be suspected in patients with elevated aminotransferase levels or radiological evidence of a fatty liver or hepatomegaly. Liver fibrosis is associated with age over 50 years, obesity, diabetes and high triglyceride levels. Liver biopsy is the only way to assess the histologic features of necrotic inflammation and fibrosis that define nonalcoholic steatohepatitis and to determine its probable prognosis. The prognosis is good for pure steatosis, whereas the presence of necrotic inflammation is associated with a significant risk of progression to cirrhosis and, possibly, hepatocellular carcinoma. Lifestyle changes, such as dietary modifications and exercise, are recommended. To date, there have been very few randomized, placebo-controlled trials of drug treatments for NAFLD.     

Nonalcoholic fatty liver disease: from lipid profile to treatment

Nonalcoholic fatty liver disease (NAFLD) is characterized by excess lipid accumulation in the liver. Although the majority of NAFLD is benign simple steatosis, a subset of NAFLD includes nonalcoholic steatohepatitis (NASH), which can progress to liver cirrhosis and liver cancer. In both simple steatosis and steatohepatitis, triglyceride is well known as the major lipid that accumulates in the liver. However, we have little information on the other lipids that deposit in the liver. Thus, lipid profiling is necessary to understand the pathogenesis of NAFLD. In addition, these data provide further information on early detection of NASH and optimal treatment for NAFLD. Although plasma and hepatic lipid profiles are similar between simple steatosis and steatohepatitis, recent intensive researches demonstrate that free cholesterol, polyunsaturated fatty acid (PUFA), and phospholipid levels are altered in human NAFLD. In experimental models, liver injury is induced by free cholesterol accumulation and compositional changes of n-6/n-3 PUFAs and phospholipids. Therefore, these lipid levels are candidates to predict the progression to NASH. Lipid-lowering agents have potential to normalize these lipid levels. Currently, favorable results are obtained using statins, ezetimibe, and n-3 PUFAs in simple steatosis. But the effects of these agents for NASH are limited. These unsatisfactory results may partially depend on the study design because most studies are relatively short-term and small number of patients. Larger studies are necessary to determine the promising effects of lipid-lowering agents for NASH and its comorbidities.     

Nonalcoholic fatty liver disease and cardiovascular disease risk

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.