Transition of an acronym from nonalcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is a global public health concern owing to its substantial contribution to chronic liver diseases. The disease is closely linked to metabolic syndrome(MS), suggesting a common biological pathway and shared disease mechanism for both ailments. Previous studies revealed a close relationship of NAFLD with the components of MS including abdominal obesity,dyslipidemia, hypertension, and hyperglycemia. Hence, a group of experts recently renamed NAFLD as metabolic dysfunction-associated fatty liver disease(MAFLD) in order to encompass a more appropriate pathogenesis of the disease.NAFLD was first named to describe a condition similar to alcoholic hepatitis in absence of significant alcohol consumption. However, knowledge pertaining to the etiopathogenesis of the disease has evolved over the past four decades. Recent evidence endorses NAFLD as a terminology of exclusion and suggests that it may often leads to misdiagnosis or inappropriate management of patients, particularly in clinical practice. On the other hand, the new definition is useful in addressing hepatic steatosis with metabolic dysfunction, which ultimately covers most of the patients with such illness. Therefore, it seems to be helpful in improving clinical diagnosis and managing high-risk patients with fatty liver disease. However, it is imperative to validate the new terminology at the population level to ensure a holistic approach to reduce the global burden of this heterogeneous disease condition.     

Non-alcoholic fatty liver disease: an overview

Non-alcoholic fatty liver disease (NAFL) includes a spectrum of clinicopathological conditions with increasing prevalence in the developed world. Although steatosis alone seems to have a benign course, those patients with the diagnosis of non-alcoholic steatohepatitis (NASH) can have a progressive course. Additionally, there is now evolving, indirect evidence that some of the patients with cryptogenic cirrhosis may be the result of 'burned-out' NASH. Although NAFL and NASH are associated with insulin-resistance syndrome, some patients with NAFL may have no obvious risk factors. Despite preliminary data from a number of pilot studies, no established therapies can be offered to patients with NASH. Over the next few years, a number of exciting research projects dealing with the epidemiology as well as the pathogenesis of NAFL are expected to be completed. It is anticipated that, through a better understanding of NAFL, more effective treatment protocols can be developed targeting only those patients with NASH that are at the highest risk for progression to cirrhosis and liver failure.     

Comparison between metabolic-associated fatty liver disease and nonalcoholic fatty liver disease: From nomenclature to clinical outcomes

As a result of the obesity epidemic, Nonalcoholic fatty liver disease(NAFLD) and its complications have increased among millions of people. Consequently, a group of experts recommended changing the term NAFLD to an inclusive terminology more reflective of the underlying pathogenesis; metabolic-associated fatty liver disease(MAFLD). This new term of MAFLD has its own disease epidemiology and clinical outcomes prompting efforts in studying its differences from NAFLD.This article discusses the rati...     

Treatment of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common cause for elevated liver enzymes in the developed nations. Beyond prevention programs which are of particular interest because of the increasing number of overweight children, treatment should be focussed on the most important risk factors, obesity and insulin resistance. As a consequence of elucidating the pathomechanisms of NAFLD, the number of potential therapeutic options increased. However, many studies investigating the therapeutic effect show shortcomings in at least one of the following points: lack of a serial liver biopsy, short term of treatment and limited number of included patients. The second generation insulin sensitizer piogiitazone and rosiglitazone show the most promising improvements in NAFLD, but weight gain and potential hepatotoxicity calls for attention. In conclusion, a general recommendation for the application of specific drugs cannot be given. Besides controlled clinical trials, weight reduction and physical activity to improve insulin sensitivity in obese patients should be the priority objective.     

Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple hepatic steatosis to steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis, a small percentage of individuals will develop progressive liver disease. Notably, both ALD and NAFLD are frequently accompanied by extrahepatic complications, including cardiovascular disease and malignancy. The survival of patients with ALD and NAFLD depends on various disease-associated conditions. This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology, the factors associated with disease susceptibility and progression, and the predictors and characteristics of outcomes. A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases.     

代谢相关脂肪性肝病肝外并发症研究进展与现状

代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)是作为描述这种疾病的一个更合适的总括述语,新的定义将代谢功能障碍列为肝病的重要病因,论证了MAFLD的高异质性,加快了向新治疗的转化路径.MAFLD的肝外并发症其发生率和相关疾病,远远超过肝病本身,严重威脅着人类健康.鉴于当前人们对其严重性认识不足,且对肝外并发病的疾病范围、发病机制、诊断的研究还不完善,尤其当前对其缺乏有效的药物治疗,有鉴于此本文就MAFLD肝外并发症研究现状与进展作一介绍与述评,与广大读者共享.     

Coronavirus disease 2019 and non-alcoholic fatty liver disease

The coronavirus disease 2019(COVID-19) pandemic may present with a broad range of clinical manifestations, from no or mild symptoms to severe disease. Patients with specific pre-existing comorbidities, such as obesity and type 2 diabetes, are at high risk of coming out with a critical form of COVID-19. Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease, and, because of its frequent association with metabolic alterations including obesity and type 2 diabetes, it has recently been re-named as metabolic-associated fatty liver disease(MAFLD). Several studies and systematic reviews pointed out the increased risk of severe COVID-19 in NAFLD/MAFLD patients. Even though dedicated mechanistic studies are missing, this higher probability may be justified by systemic low-grade chronic inflammation associated with immune dysregulation in NAFLD/MAFLD, which could trigger cytokine storm and hypercoagulable state after severe acute respiratory syndrome coronavirus 2 infection. This review focuses on the predisposing role of NAFLD/MAFLD in favoring severe COVID-19, discussing the available information on specific risk factors, clinical features, outcomes, and pathogenetic mechanisms.     

Comparative redox status in alcoholic liver disease and nonalcoholic fatty liver disease

Purpose Altered redox status has been implicated in pathogenesis of alcoholic liver disease (ALD) as well as in nonalcoholic fatty liver disease (NAFLD). This study was planned to find the relative role of redox status in these two diseases. Methods A total of 44 patients with ALD and 32 patients with NAFLD and 25 apparently healthy controls were included in the study. Redox status was estimated by measuring oxidative stress (superoxide dismutase (SOD) and lipid peroxidation products as thiobarbituric acid reactive substances (TBARS)) and antioxidant status (ferric reducing ability of plasma (FRAP) and vitamin C). Results TBARS level was raised significantly in both ALD (3.5 (2.3–9.4) vs. 1.8 (0.5–4.1) nmol/ml; P = 0.0001) and NAFLD (5.1 (1–10.2) vs. 1.82 (0.51–4.1) nmol/ml; P = 0.0001) as compared with controls, but was not different between ALD and NAFLD. SOD was significantly higher in ALD as compared to NAFLD (2.4 (1.3–7.8) vs. 0.68 (0.05–19.1) U/ml; P = 0.0001) and controls (1.12 (0.01–3.5) U/ml; P = 0.001). FRAP was lower in ALD as compared with NAFLD (345.4 (56–615.9) vs. 434.1 (197.6–733.3) μmol of Fe⁺² liberated; P = 0.001) but similar to that of controls (340.9 (141.5–697.5) μmol of Fe⁺² liberated). Conclusions ALD patients have a higher degree of redox imbalance as compared with NAFLD patients     

内毒素与脂肪肝的关系研究进展

脂肪肝时常伴有肠源性内毒素血症,内毒素不仅对肝细胞有直接的损伤作用,而且可通过激活库普弗细胞(KC)释放一系列生物活性物质,以及可能促进肝脏自然杀伤T细胞减少,导致促炎和抗炎免疫反应失衡,引起肝脏损害,从而加重内毒素的作用.     

非酒精性脂肪肝和心血管疾病

非酒精性脂肪肝(NAFLD)是临床慢性肝脏疾病,包括单纯的肝细胞脂肪变、脂肪性肝炎(NASH)、肝脏纤维化甚至肝硬化等,是临床隐原性肝硬化最常见的病因。胰岛素抵抗(IR)和中央性肥胖是NAFLD的重要发病机制。同时由中央性肥胖、2型糖尿病、胰岛素抵抗、高血压及血脂异常等组成的代谢综合征(MS)是心血管疾病(CVD)的高危险因素。现在,越来越多的研究认为NAFLD是MS在肝脏系统的表现,NAFLD的出现可能不仅仅是CVD发生的标志,甚至是CVD的早期中间状态。     

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.     

脂肪因子与非酒精性脂肪肝

非酒精性脂肪性肝病的发病机制目前尚不十分清楚,脂代谢异常(尤其是TG)与胰岛素抵抗(IR)可能是其病因的关键环节,瘦素、脂联素、抵抗素、肿瘤坏死因子等多种脂肪因子在非酒精性脂肪肝的形成、炎性改变及纤维化的过程中发挥了重要作用.     

Genes or environment to determine alcoholic liver disease and non-alcoholic fatty liver disease.

While the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome will have steatosis, only a minority will ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of fibrosis. For ALD, the dose and pattern of alcohol intake, along with obesity are the most important environmental factors determining disease risk. For NAFLD, dietary saturated fat and antioxidant intake and small bowel bacterial overgrowth may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the alcohol dehydrogenases and aldehyde dehydrogenase alcohol metabolising genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, TNF-alpha, transforming growth factor-beta, and angiotensinogen may be associated with steatohepatitis and/or fibrosis.     

非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病经历由非酒精性单纯性脂肪肝发展至非酒精性脂肪性肝炎和肝硬化或原发性肝癌的缓慢过程,并与心血管病的发生关系密切.本文针对非酒精性脂肪性肝病的流行病学、发病机制、诊断和治疗等的研究进展进行综述.     

非酒精性脂肪性肝病与代谢综合征相关性的临床研究

目的分析非酒精性脂肪性肝病与代谢综合征的关系。方法按住院顺序选择有随访资料病例共185例,将其分为四组（单纯脂肪肝组、单纯肥胖组、脂肪肝＋肥胖组、正常对照组）,在基线水平对四组出现代谢综合征情况进行横向比较。其次,在随访后再次对四组出现代谢综合征情况进行组内、组间比较。结果随访结束时,单纯脂肪肝组代谢综合征发病率明显高于正常对照组（P〈0.05）。结论非酒精性脂肪性肝病促进代谢综合征的发生,且不依赖于肥胖。     

Non-alcoholic fatty liver disease in 2015

There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase.     

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。