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.     

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 and HFE gene mutations: A Polish study

AIM:To describe a Polish population with nonalcoholic fatty liver disease(NAFLD)with regard to HFE gene mutations,as well as analyzing demographic and clinical data.METHODS:Sixty-two consecutive patients with biopsy-proven NAFLD were included in the study.Demographic,clinical,and laboratory data were summarized in a database.C282Y and H63D mutations of the HFE gene were analyzed using polymerase chain reactionrestriction fragment lenght polymorphism.RESULTS:The analyzed cohort consisted of 62 homo-geneic Ca...     

Nonalcoholic steatohepatitis in nonalcoholic fatty liver disease patients of Bangladesh

AIM: To explore the prevalence and risk factors for nonalcoholic steatohepatitis (NASH) in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: We have included 493 patients with sonographic evidence of a fatty change, and 177 of these individuals were evaluated and confirmed after liver biopsy. The exclusion criteria consisted of significant alcohol abuse (< 20 g daily), evidence of hepatitis B and C, evidence of drug-induced fatty liver disease and other specific liver diseases such as hemochromatosis, Wilson’s disease or autoimmune liver disease. The patients were assessed for metabolic syndrome, and biochemical, anthropometric and histopathological evaluations were carried out. The degree of disease activity in the NAFLD patients was evaluated using the NAFLD Activity Score. The data were analyzed by SPSS, version 16.0. RESULTS: Females predominated among the study participants (250, 57.0%), and the mean age was 40.8 ± 10.2 years. The numbers of overweight, obeseⅠ and obese Ⅱ patients were 58 (13.2%), 237 (53.9%) and 93 (21.2%), respectively. However, there were 422 (96.2%) centrally obese patients. NASH was absent in 10 (5.6%) cases, borderline in 92 (52.6%) cases and present in 75 (42.4%) cases. The presence of diabetes could significantly (P = 0.001) differentiate NASH from simple steatosis. The following parameters did not influence the development of NASH: age, sex, basal metabolic index, waist circumference, serum high-density lipoprotein, triglyceride, insulin resistance index, hypertension and metabolic syndrome. The serum gammaglutamyl transpeptidase (GGT) level was significantly higher (P = 0.05, 51.7 ± 32.8 and 40.4 ± 22.6 U/L) in the NASH patients, with a sensitivity of 45% and a specificity of only 68%. The serum alanine aminotransferase and aspartate aminotransferase levels were not able to predict NASH. CONCLUSION: Females were the predominant sufferers of NAFLD in Bangladesh. The prevalence of NASH was high. Diabetes was found to be the main culprit in developing NASH. GGT was the only biochemical marker of NASH. We recommend liver biopsy in NAFLD patients who have diabetes and elevated GGT.     

Nonalcoholic fatty liver disease in developing countries

TO THE EDITOR Nonalcoholic fatty liver disease (NAFLD) is an increasingly known medical entity with high prevalence, about 1 0 to 24 percent in general population and up to 74% in obese population[1]. The prevalence of the disease is expected to increase worldwide, as we are encountering the global obesity epidemic and the trend in developing countries toward the Western lifestyles. However, it looks that there are some differences between the demographic and epidemiologic features of NAFLD in developing and developed countries.     

Nonalcoholic fatty liver disease: pharmacologic and surgical options

The last decade has seen many studies examining the prevalence and natural history of NAFLD in the United States and it is clear that this disease is likely to be an important cause of liver-related morbidity in the future. Several pharmacologic therapies have shown some promise; currently, vitamin E and insulin-sensitizing agents such as pioglitazone can be considered in appropriate cases. Conservative measures to promote weight loss still have a role to play, but the obesity epidemic in the Western World has reached such proportions that bariatric surgery is proving to be an attractive option for patients with a BMI greater than 35 to 40 kg/m2. Well-designed prospective studies are required to ensure that all of these therapies are safe and effective in the long term. Newer agents will likely be investigated as the pathogenesis of NAFLD and fibrosis progression in NASH are further elucidated.     

Histopathology of nonalcoholic fatty liver disease

Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease(NAFLD) are measured.Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD,i.e.nonalcoholic steatohepatitis(NASH) and fibrosis.Included in the lesions of NAFLD are steatosis,lobular and portal inflammation,hepatocyte injury in the forms of ballooning and apoptosis,and fibros...     

Nonalcoholic fatty liver disease as a multi-systemic disease

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD includes a wide spectrum of liver conditions ranging from simple steatosis to nonalcoholic steatohepatitis and advanced hepatic fibrosis. NAFLD has been recognized as a hepatic manifestation of metabolic syndrome linked with insulin resistance. NAFLD should be considered not only a liver specific disease but also an early mediator of systemic diseases. Therefore, NAFLD is usually associated with cardiovascular disease, chronic kidney disease, type 2 diabetes, obesity, and dyslipidemia. NAFLD is highly prevalent in the general population and is associated with increased cardiovascular morbidity and mortality. The underlying mechanisms and pathogenesis of NAFLD with regard to other medical disorders are not yet fully understood. This review focuses on pathogenesis of NAFLD and its relation with other systemic diseases.     

Nonalcoholic fatty liver disease and risk of intracerebral hemorrhage

Background and aimsThis study aimed to investigate the association between the steatosis severity of nonalcoholic fatty liver disease (NAFLD) and future intracerebral hemorrhage (ICH) risk.Methods and resultsWe used data from the Kailuan study. Participants without a history of stroke, myocardial infarction, cancer, other liver diseases or alcohol abuse were enrolled. NAFLD and the severity of liver steatosis were assessed by abdominal ultrasonography. We stratified the participants into different groups according to the severity changes in liver steatosis status across the first 4-year follow-up period. The outcome was the first occurrence of ICH during the next 6-year follow-up period. Hazard ratios (HRs) and 95% CI of ICH were estimated using Cox models adjusted for potential risk factors. A total of 49,906 participants were enrolled in this study. During a median of 6.79 years of follow-up, 193 incident ICH cases were identified. Compared with persistent nonfatty liver participants, the hazard ratios (HRs) for participants with persistent mild steatosis, persistent moderate steatosis, persistent severe steatosis, alleviating steatosis, and aggravating steatosis were 1.28 (95% CI, 0.75–2.18), 2.33 (95% CI, 1.24–4.38), 1.63 (95% CI, 0.22–12.11), 1.41 (95% CI, 0.91–2.18), and 1.37 (95% CI, 0.94–2.00), respectively, in the fully adjusted model.ConclusionsNAFLD with persistent moderate steatosis was significantly related to an increased risk of future ICH, independent of other conventional risk factors.     

Advances in paediatric nonalcoholic fatty liver disease: Role of lipidomics

Due its close relationship with obesity, nonalcoholic fatty liver disease (NAFLD) has become a major worldwide health issue even in childhood. The most accepted pathophysiological hypothesis is represented by the “multiple hits” theory, in which both hepatic intracellular lipid accumulation and insulin resistance mainly contribute to liver injury through several factors. Among these, lipotoxicity has gained particular attention. In this view, the pathogenic role of different lipid classes in NAFLD (e.g., sphingolipids, fatty acids, ceramides, etc.) has been highlighted in recent lipidomics studies. Although there is some contrast between plasma and liver findings, lipidomic profile in the NAFLD context provides novel insights by expanding knowledge in the intricate field of NAFLD pathophysiology as well as by suggesting innovative therapeutic approaches in order to improve both NAFLD prevention and treatment strategies. Selective changes of distinct lipid species might be an attractive therapeutic target for treating NAFLD. Herein the most recent evidence in this attractive field has been summarized to provide a comprehensive overview of the lipidomic scenario in paediatric NAFLD.     

Oxidative stress,cardiolipin and mitochondrial dysfunction in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is today considered the most common form of chronic liver disease, affecting a high proportion of the population worldwide. NAFLD encompasses a large spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Obesity, hyperglycemia, type 2 diabetes and hypertriglyceridemia are the most important risk factors. The pathogenesis of NAFLD and its progression to fibrosis and chronic liver disease is still unknown. Accumulating evidence indicates that mitochondrial dysfunction plays a key role in the physiopathology of NAFLD, although the mechanisms underlying this dysfunction are still unclear. Oxidative stress is considered an important factor in producing lethal hepatocyte injury associated with NAFLD. Mitochondrial respiratory chain is the main subcellular source of reactive oxygen species(ROS), which may damage mitochondrial proteins, lipids and mitochondrial DNA. Cardiolipin, a phospholipid located at the level of the inner mitochondrial membrane, plays an important role in several reactions and processes involved in mitochondrial bioenergetics as well as in mitochondrial dependent steps of apoptosis. This phospholipid is particularly susceptible to ROS attack. Cardiolipin peroxidation has been associated with mitochondrial dysfunction in multiple tissues in several physiopathological conditions, including NAFLD. In this review, we focus on the potential roles played by oxidative stress and cardiolipin alterations in mitochondrial dysfunction associated with NAFLD.     

Nonalcoholic fatty liver disease in asymptomatic Brazilian adolescents

AIM： To evaluate the prevalence and clinical characteristics of Nonalcoholic fatty liver disease （NAFLD） among asymptomatic Brazilian adolescents. METHODS： Transversal observational study included asymptomatic adolescents with central obesity from private and public schools in Salvador-Bahia, northeastern Brazil. The children answered a questionnaire that in- cluded age, gender, race, and medical history, and were submitted to a complete physical exam and abdominal ultrasound. Biochemical exams included： ALT, AST, GGT, C reactive protein （CRP）, fasting glucose, insulin, cholesterol and triglycerides. Criteria for NAFLD included： the presence of steatosis in ultrasound and/or high level of ALT, negative or occasional historic of intake of alcohol （4 140 g/wk）, negative investigation for hepatitis A, B, C, auto-immune hepatitis, Wilson disease and hemochro-matosis.RESULTS： From October, 2005 to October, 2006, the study included 1801 subjects between 11 and 18 years of age and a mean age of 13.7± 2.0 years. One hun- dred ninety-nine had central obesity. The prevalence of NAFLD was 2.3%, most of whom were male and white. Insulin resistance （IR） was observed in 22.9% of them and had positive correlations with ALT and GGT （P 〈 0.05）. Elevated CRP was observed in 6.9% of the cases; however, it was not associated with WC, IR or liver enzymes. CONCLUSION： The prevalence of NAFLD in Brazilian adolescents was low. The ethnicity may have influence this frequency in the population studied, which had a large proportion of African descendents.     

Nonalcoholic fatty liver disease in patients with inflammatory bowel disease: Beyond the natural history

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) is a frequently reported condition in patients with inflammatory bowel disease(IBD). Both intestinal inflammation and metabolic factors are believed to contribute to the pathogenesis of IBDassociated NAFLD.AIM To evaluate the prevalence of steatosis and liver fibrosis(LF) in a cohort of IBD patients and the identification of metabolic-and IBD-related risk factors for NAFLD and LF.METHODS IBD patients were consecutively enrolled from December 2016 to January 2018.Demographic, anthropometric and biochemical data were collected so as eating habits. Abdominal ultrasound and transient elastography were performed to evaluate the presence of NAFLD and LF respectively.RESULTS A total of 178 consecutive patients were enrolled and included in the analysis(95 Ulcerative colitis, 83 Crohn's disease). NAFLD was detected by imaging in 72(40.4%) patients. Comparison between patients with and without NAFLD showed no significant differences in terms of IBD severity, disease duration,location/extension, use of IBD-related medications(i.e., steroids, anti-TNFs, and immunomodulators) and surgery. NAFLD was significantly associated with thepresence of metabolic syndrome [MetS; odds ratio(OR): 4.13, P = 0.001] and obesity defined by body mass index(OR: 9.21, P = 0.0002). IBD patients with NAFLD showed higher caloric intake and lipid consumption than those without NAFLD, regardless disease activity. At the multivariate analysis, male sex,advanced age and high lipid consumption were independent risk factors for the development of NAFLD. An increased liver stiffness was detected in 21 patients(16%) and the presence of MetS was the only relevant factor associated to LF(OR:3.40, P = 0.01).CONCLUSION In this study, we demonstrate that risk factors for NAFLD and LF in the IBD population do not differ from those in the general population.     

2型糖尿病合并非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病(NAFLD)是以肝细胞脂肪变性和脂肪蓄积为病理特征,但无过量饮酒史的临床综合征,它是代谢综合征在肝脏的表现.胰岛素抵抗是NAFLD与2型糖尿病的共同发病基础.NAFLD是转氨酶慢性升高的常见原因之一.转氨酶升高在2型糖尿病患者中的发生率明显高于普通人群,并与心血管危险因素的聚集有关.运动和节制饮食可控制体重、改善胰岛素抵抗、纠正血脂紊乱和减轻脂肪肝.二甲双胍和格列酮类可降低血转氨酶水平和部分逆转脂肪肝组织学变化.     

脂肪肝指数在非酒精性脂肪性肝病诊断中的应用价值

目的:通过评估脂肪肝指数(FLI),探讨其对非酒精性脂肪性肝病(NAFLD)的筛查和诊断价值。方法:选取年龄大于40岁的上海嘉定地区常住居民共2 519人,通过问卷调查、体格检查及相关人体测量学和生化学指标检测,综合评估人群代谢状态并计算个体FLI。通过高分辨率超声诊断NAFLD。利用受试者工作特征(ROC)曲线评估FLI对于经超声诊断的NAFLD的预测价值。结果:最终共有2 139名受试者纳入统计分析。FLI作为诊断NAFLD的ROC曲线下面积为0.84,95%可信区间为0.82～0.86。当FLI≥30时,其诊断NAFLD的敏感性和特异性最好,灵敏度和特异度分别达到80.6%和73.8%。结论:FLI对于NAFLD的诊断具有较高的参考价值,适用于大样本流行病学研究及指导NAFLD的早期干预和治疗。     

性激素在非酒精性脂肪性肝病发病机制中的作用

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一类由遗传-环境-代谢应激相关因素所致的,以弥漫性肝细胞大泡性脂肪变性和肝小叶内炎症为主要特征的临床病理综合征.近年来,随着研究深入,发现NAFLD不仅与肝脏脂质代谢紊乱、胰岛素抵抗(insulin resistance,IR)、氧化应激、内毒素血症等相关,其发生还存在明显性别差异,推测其可能与不同性别间性激素水平、肝脂代谢差异以及糖脂代谢酶表达及活性差异等多种因素相关[1].现结合近年来国内外最新文献,就性激素在NAFLD患者中的变化及其对NAFLD发病的影响和作用机制作一简要综述. 一、NAFLD流行病学与性别差异 Hepatology于2011年发表了澳大利亚一项最新研究结果,1170例青少年中,NAFLD发病率为12.8％,其中男女比例约为1:1.6[2].该结论与多项国内外研究结果显示的男性脂肪肝患病率高于女性相悖,分析其原因可能与不同研究人口基础特征、ALT水平及不同性别人群肥胖比例差异等相关[3].有关NAFLD性别差异的研究结果显示,整体人群中,男性NAFLD患者高于女性,但青春期前及50岁以后女性发病率明显高过男性,说明女性激素可能对生育期女性脂肪肝的发生起保护作用.     

Promising diagnostic biomarkers of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: From clinical proteomics to microbiome

Fatty liver has been present in the lives of patients and physicians for almost two centuries. Vast knowledge has been generated regarding its etiology and consequences, although a long path seeking novel and innovative diagnostic biomarkers for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is still envisioned. On the one hand, proteomics and lipidomics have emerged as potential noninvasive resources for NAFLD diagnosis. In contrast, metabolomics has been able to distinguish between NAFLD and NASH, even detecting degrees of fibrosis. On the other hand, genetic and epigenetic markers have been useful in monitoring disease progression, eventually functioning as target therapies. Other markers involved in immune dysregulation, oxidative stress, and inflammation are involved in the instauration and evolution of the disease. Finally, the fascinating gut microbiome is significantly involved in NAFLD and NASH. This review presents state-of-the-art biomarkers related to NAFLD and NASH and new promises that could eventually be positioned as diagnostic resources for this disease. As is evident, despite great advances in studying these biomarkers, there is still a long path before they translate into clinical benefits.