非酒精性脂肪性肝病研究新进展

非酒精性脂肪性肝病( non- alcoholic fatty liver disease,NAFLD)是指除外酒精和其他明确的肝损害因素所致的,以弥漫性肝细胞大泡性脂肪变为主要特征的临床病理综合征,包括单纯性脂肪性肝病以及由其演变的脂肪性肝炎和肝硬化.NAFLD是21世纪全球重要的公共健康问题之一,也是常见的慢性肝病.     

酒精性与非酒精性脂肪性肝病

脂肪性肝病(FLD)根据有无过量饮酒史,分为酒精性肝病(ALD)和非酒精性脂肪性肝病(NAFLD)两大类。两者享有FLD的许多共性特征,但又各有其独特之处。 1.酒精性与非酒精性FLD的异同:NAFLD的肝组织学改变与ALD相似,包括单纯性脂肪肝、脂肪性肝炎及肝硬化。我国及日本学者认为ALD还应包括轻症ALD、酒精性重型肝炎及酒精性肝纤维化,事实上NAFLD均有其相对应的临床病理类     

非酒精性脂肪性肝病治疗进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)已成为目前全球最主要的慢性肝病病因,是当前研究的热点问题,其预防和治疗也成了研究的重点和难点,目前尚无批准上市的特异性药物及明确的治疗方案,本文针对NAFLD的相关治疗及新兴靶向药物作一概述,给临床医师提供参考。     

非酒精性脂肪性肝病诊断的研究进展

非酒精性脂肪性肝病(NAFLD)是指除外乙醇和其他明确肝损伤因素所致的以肝细胞内脂肪过度沉积为主要特征的临床病理综合征,是与胰岛素抵抗和遗传易感性密切相关的获得性代谢应激性肝损伤,主要影响肝脏以外的器官代谢和免疫通路的作用,是代谢综合征在肝脏的表现。NAFLD在全球范围内高度流行,早期诊断及评估肝脏脂肪变性程度和纤维化程度对NAFLD患者的早期治疗和预后判断具有重要意义。该文总结了各种影像学技术及标志物对于NAFLD诊断的重要意义,以期为临床应用提供参考。     

非酒精性脂肪性肝病治疗进展

非酒精性脂肪性肝病无特效治疗方法,目前以生活方式调节为基础,必要时辅以药物治疗。本文从生活方式调节和药物治疗两方面回顾近年来的治疗研究进展。     

非酒精性脂肪性肝病治疗策略

非酒精性脂肪性肝病（NAFLD）是指除外酒精和其他明确的损肝因素所致的,以弥漫性肝细胞大泡性脂肪变为主要特征的临床病理综合征,包括单纯性脂肪肝以及由其演变的非酒精性脂肪性肝炎（NASH）和肝硬化。在欧美等发达国家,NAFLD发病率可达到20％～30％,在亚太地区成人NAFLD患病率亦达到12％～24％,而且目前仍呈上升趋势。     

美国非酒精性脂肪性肝病诊疗指南简介

2012年2月22日,美国肝脏病学会、美国胃肠病学院和美国胃肠病学会共同起草了《非酒精性脂肪性肝病诊疗指南》,并于2012年4月6日全文在《Hepatology》杂志在线发表。我们将推荐意见翻译成中文（括号内的“1或2”为推荐强度,“A、B或C”为证据的等级或质量）,供大家学习参考。     

药物治疗非酒精性脂肪性肝病进展

非酒精性脂肪性肝病(NAFLD)是发达国家引起肝功能异常最常见的原因,治疗的重点在于阻止疾病的进展,去除引起代谢综合征的危险因素,如肥胖、胰岛素抵抗及血脂紊乱等.随着NAFLD的发病机制逐渐揭示,可选择的治疗方法除减肥外,药物治疗有抗氧化剂、胰岛素增敏剂、降脂药和肝脏保护剂.本文重点对药物治疗的进展做一综述.     

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.     

Clinicopathological significance of oxidative cellular damage in non-alcoholic fatty liver diseases.

Oxidative stress may play an important role in the progression of simple steatosis to non-alcoholic steatohepatitis (NASH). Oxidative stress is generated through multiple sources, including oxidation of free fatty acids, cytochrome P4502E1, iron overload, and necro-inflammatory cytokines including tumor necrosis factor-alpha. Oxidative stress may trigger damage to cellular membranes and nuclear DNA, which results in lipid peroxidation and oxidative DNA damage, respectively. Here, we present our data on intrahepatic localization and clinico-pathological significance of oxidative stress-induced cellular damage in the patients with non-alcoholic fatty liver diseases (NAFLD). Our subjects were 23 patients with non-alcoholic simple fatty liver, 17 with NASH, and 7 with normal liver (control). Hepatic expression of 4-hydroxy-2'-nonenal (HNE) and 8-hydroxydeoxyguanosine (8-OHdG), as reliable markers of lipid peroxidation and oxidative DNA damage, was in situ detected by using commercially available monoclonal antibodies. While no HNE adducts were observed in control livers, they were frequently detected in NAFLD. In NASH, the localization of the HNE adducts was in the cytoplasm of sinusoidal cells and hepatocytes with a predominance in zone 3. The grade of necro-inflammation as well as the stage of fibrosis significantly correlated with the HNE labeling index. With respect to 8-OHdG, although no 8-OHdG expression was observed in normal liver and only a few in non-alcoholic simple fatty liver, 11 of 17 patients with NASH (65%) exhibited nuclear expression of 8-OHdG in hepatocytes and sinusoidal cells in areas of active inflammation. The 8-OHdG index significantly correlated with the grade of necro-inflammation, but not with the stage of fibrosis. Our observations suggest that oxidative cellular damage occurs frequently in livers with NAFLD and may be associated with some clinico-pathological features of NAFLD including liver fibrosis and possibly, hepatocarcinogenesis.     

Significance of gut microbiota in alcoholic and non-alcoholic fatty liver diseases

Liver-gut communication is vital in fatty liver diseases, and gut microbes are the key regulators in maintaining liver homeostasis. Chronic alcohol abuse and persistent overnutrition create dysbiosis in gut ecology, which can contribute to fatty liver disease. In this review, we discuss the gut microbial compositional changes that occur in alcoholic and nonalcoholic fatty liver diseases and how this gut microbial dysbiosis and its metabolic products are involved in fatty liver disease pathophysiology. We also summarize the new approaches related to gut microbes that might help in the diagnosis and treatment of fatty liver disease.     

过氧化物酶体增殖物活化受体与非酒精性脂肪性肝病

非酒精性脂肪性肝病(NAFLD)的发病率正在逐年升高,肝脏脂肪沉积是NAFLD的临床病理特征和诊断的金标准.过氧化物酶体增殖物活化受体(PPARs)是配体激活的核受体,在脂代谢、糖代谢和炎性反应中起关键作用,其可作为治疗NAFLD的靶点.PPARs激动剂可减少肝内脂肪沉积,从而逆转NALFD的发展进程,但因其尚存在较多不良反应,所以对PPARs与NAFLD的机制需要进一步研究,从而为PPARs治疗NAFLD提供更有力的证据.     

二十二碳六烯酸治疗非酒精性脂肪性肝病患者疗效观察*

目的 探讨饮食补充二十二碳六烯酸（DHA）是否能改善非酒精性脂肪性肝病（NAFLD）患者的肝功能指标和血清成纤维细胞生长因子21（FGF21）水平的变化。方法 将36例NAFLD患者分为对照组、小剂量（250 mg.day-1)和大剂量（500 mg.day-1）DHA治疗组,每组12例,观察6个月。常规检测空腹血糖（FPG）、空腹胰岛素（FINS）、游离脂肪酸（FFA）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）,计算胰岛素敏感指数（ISI）;采用酶联免疫法检测血清FGF21水平。结果 DHA治疗患者血脂水平降低明显优于对照组,且大剂量治疗组更明显;对照组患者血清FINS、ISI和FGF21分别为（13.4±2.6）mU/L、（-4.2±0.2）和（1.8±0.5） ng/ml,与大剂量DHA治疗患者[分别为（8.4±2.1） mU/L、（-3.7±0.2）和（1.4±0.4） ng/ml,P<0.05]比,差异显著。结论 饮食补充DHA可显著改善非酒精性脂肪性肝病患者血脂水平,其机制可能与提高胰岛素敏感性,降低FGF21因子水平有关。     

非酒精性脂肪性肝病与肠道菌群失调新观点

非酒精性脂肪性肝病（NAFLD）在世界范围内患病率逐渐升高,“二次打击学说”发病机制已经被认可,但是具体的病理生理学发病机制还不完全清楚。近期,已有大量研究的新观点来解释肠道菌群在 NAFLD 发病机制中的作用,包括调节肠粘膜通透性、低水平炎症反应和免疫平衡,调节饮食胆碱代谢,调节胆汁酸代谢和增加细菌产生的内源性乙醇等。这些因素在分子水平上解释了肠道菌群如何促发 NAFLD 的发生,并进一步诱导其向非酒精性脂肪性肝炎（NASH）进展。     

Pediatric non-alcoholic fatty liver disease: Recent solutions,unresolved issues,and future research directions

Non-alcoholic fatty liver disease(NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance(IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis(NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data(BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR(acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy(the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention.Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle changes. When morbid obesity prevails, bariatric surgery should be considered.     

Management of non-alcoholic fatty liver disease in 2015

There is no single pharmacologic therapy that has been approved to treat nonalcoholic fatty liver disease in the general population. The backbone of therapy currently includes intensive lifestyle modification with established targets for diet and weight loss. The use of unsweetened, unfiltered coffee along with limiting high fructose corn syrup have emerged as beneficial dietary recommendations. The use of empiric oral hypoglycemic agents and vitamin E, however, has not been widely accepted. Developing bariatric surgical techniques are promising, but additional studies with long-term follow up are needed before it can be widely recommended. Finally, liver transplantation is an increasingly frequent consideration once complications of end-stage disease have developed. The future treatment of those with nonalcoholic fatty liver disease will likely involve a personalized approach. The importance of the gut microbiome in mediating hepatocyte inflammation and intestinal permeability is emerging and may offer avenues for novel treatment. The study of anti-fibrotic agents such as pentoxifylline and FXR agonists hold promise and new pathways, such as hepatocyte cannabinoid receptor antagonists are being studied. With the incidence of obesity and the metabolic syndrome increasing throughout the developed world, the future will continue to focus on finding novel agents and new applications of existing therapies to help prevent and to mediate the progression of nonalcoholic fatty liver disease.     

Lipidomics in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disorder in Western countries, comprises steatosis to nonalcoholic steatohepatitis (NASH), with the latter having the potential to progress to cirrhosis. The transition from isolated steatosis to NASH is still poorly understood, but lipidomics approach revealed that the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis and these alterations correlate with disease progression. Recent data suggest that both quantity and quality of the accumulated lipids are involved in pathogenesis of NAFLD. Changes in glycerophospholipid, sphingolipid, and fatty acid composition have been described in both liver biopsies and plasma of patients with NAFLD, implicating that specific lipid species are involved in oxidative stress, inflammation, and cell death. In this article, we summarize the findings of main human lipidomics studies in NAFLD and delineate the currently available information on the pathogenetic role of each lipid class in lipotoxicity and disease progression.     

运动防治非酒精性脂肪性肝病的机制

非酒精性脂肪性肝病(NAFLD)目前已经成为全球流行的慢性肝脏疾病.运动能够改善NAFLD.研究证实,运动能够减轻肝脏脂肪沉积及炎性反应,但其具体机制尚不明确,有待进一步研究.