非酒精性脂肪肝的治疗

非酒精性脂肪肝包括单纯性脂肪肝和非酒精性脂肪性肝炎（NASH）。非酒精性脂肪性肝炎（NASH）是在1980年由Ludwig等从病理学角度提出的,是指病理学上和酒精性肝炎相似,但无过量饮酒史的病理状态。非酒精性脂肪肝作为肝硬化和终末期肝病病因之一日益受到重视,     

非酒精性脂肪肝的治疗

非酒精性脂肪肝包括单纯性脂肪肝和非酒精性脂肪性肝炎（NASH）。非酒精性脂肪性肝炎（NASH）是在1980年由Ludwig等从病理学角度提出的，是指病理学上和酒精性肝炎相似，但无过量饮酒史的病理状态。非酒精性脂肪肝作为肝硬化和终末期肝病病因之一日益受到重视，但其确切病因尚不清楚。至今也尚无完全有效的药物治疗措施。能够做到的仅仅是改善胰岛素抵抗，     

非酒精性脂肪肝中医药干预研究

非酒精性脂肪肝(NAFLD)是一类肝组织学改变,与酒精性肝病相似,但无过量饮酒史的临床病理综合征,包括非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎和非酒精性脂肪性肝硬化3种主要类型。近年来随着人们生活习惯和饮食结构的改变,临床B     

走出脂肪肝防治误区

脂肪肝一词源自病理学，系指肝脏弥漫性脂肪浸润，根据是否伴有炎症、坏死和纤维化，分为单纯性脂肪肝、脂肪性肝炎及脂肪性肝硬化。脂肪性肝病则是临床概念，反映广谱的与遗传一环境一代谢应激相关的疾病，根据有无过量饮酒史分为酒精性和非酒精性脂肪性肝病，后者主要与肥胖、糖尿病和高脂血症有关。     

非酒精性脂肪性肝病基因多态性研究

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)已经成为常见的肝脏疾病之一,包括单纯性脂肪肝、脂肪性肝炎(NASH)、脂肪性肝纤维化和脂肪性肝硬化4个病理过程。单纯性脂肪肝预后良好,脂肪性肝炎部分可以发展为肝硬化和肝癌。Browning等对美国2287例城     

脂肪性肝病2010年度回顾

脂肪性肝病是一种遗传-环境-代谢应激相关的临床病理综合征,疾病谱包括单纯性脂肪肝、脂肪性肝炎及其相关肝硬化和肝细胞癌。脂肪性肝病的诊断需包括病因以及疾病的分级和分期。根据病因,脂肪性肝病可分为酒精性肝病、非酒精性脂肪性肝病以及特殊原因所致脂肪肝。     

简讯

调节性T细胞有望成为治疗脂肪性肝炎的新途径2007年11月,国际肝病研究领域权威学术杂志《肝脏病学》》(《Hepatology》,影响因子10.45)刊登了我国学者与美国科学家合作的最新发现,报道了脂肪性肝炎与调节性T细胞之间关系的论文。该项研究课题负责人之一、上海市消化疾病研究所副所长、上海市脂肪性肝病诊治研究中心副主任、上海交通大学医学院附属仁济医院消化内科马雄副教授介绍,在临床上,常将非酒精性脂肪性肝病分为单纯性脂肪肝、脂肪性肝炎和脂肪性肝炎相关肝硬化。单纯性脂肪肝相对稳定,其中10%~20%可进展为脂肪性肝炎,而脂肪性肝炎…     

糖尿病合并脂肪肝的防治策略

非酒精性脂肪性肝病(NAFLD)是与胰岛素抵抗(IR)密切相关的代谢性肝脏损害,病理学改变以肝细胞脂肪变性为主,包括非酒精性单纯性脂肪肝(NAFL)、非酒精性脂肪性肝炎(NASH)、NASH相关性肝硬化及肝细胞癌。     

非酒精性脂肪性肝病的病因、诊断及防治

正一、什么是非酒精性脂肪性肝病随着我国生活水平的改善和生活方式的改变,非酒精性脂肪性肝病的发病率不断升高,现已成为我国常见的慢性肝病之一。非酒精性脂肪性肝病是指除外酒精和其他明确的损肝因素所致的肝细胞内脂肪过度沉积为主要特征的临床病理综合征,其疾病谱包括单纯性脂肪肝、脂肪性肝炎及其相关肝硬化。     

非酒精性脂肪肝30例临床分析

非酒精性脂肪肝病（NAFLD）,又称非酒精性脂肪肝（NAFL）,是一种无过量饮酒史,以肝实质细胞脂肪变性和脂肪贮积为特征的临床病理综合症。NAFLD已成为常见肝病之一,疾病谱随病程的进展表现不一,主要包括抵单纯性脂肪肝、脂肪性肝炎、脂肪性肝纤维化和肝硬化。随着人们生活水平的改善和生活方式的改善,脂肪性肝病的发生率不断升高。据报道其发病率可高达10％,而且发病年龄日趋提前。近年国外几个对脂肪性肝炎的前瞻性研究显示,部分脂肪性肝炎可发展为肝硬化。     

非酒精性脂肪性肝病动物模型研究进展

非酒精性脂肪性肝病(NAFLD)是一种无酒精滥用的肝病综合征,包括单纯性脂肪肝、脂肪性肝炎、脂肪性肝纤维化和肝硬变.目前由于发病率高,治疗困难,已成为广受关注的医学难题.由于NAFLD的发病机制尚未完全明确,临床治疗上也缺乏有效措施,因此建立高质量的动物模型对于该疾病的发病机制和药物治疗研究有重大意义.本文综述了近年来用于研究NAFLD的动物模型,介绍其制作方法和特点.     

非酒精性脂肪性肝病的临床表现与病理学特点

非酒精性脂肪性肝病(NAFLD)与胰岛素抵抗和代谢综合征有关。临床上可表现为无症状性氨基转移酶增高或肝硬化并发症和肝癌。组织学表现为单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)或进展为肝纤维化和肝硬化。超声与CT检查可以识别肝脏脂肪沉积,但不能区分单纯性脂肪肝与NASH,需要借助肝穿刺组织病理学检查进一步确诊。本文就NAFLD的临床表现和病理学特点进行综述。     

长爪沙鼠NAFLD模型的建立及其遗传学的研究

非酒精性脂肪性肝病(NAFLD)已成为目前主要代谢性疾病之一,针对传统的动物模型的缺陷,本研究首次建立了与人类NAFLD(从单纯脂肪肝到脂肪性肝炎,再进展到肝纤维化、肝硬化)极为相似、饲料配方简便的长爪沙鼠NAFLD模型,阐明了长爪沙鼠肝脏脂肪快速沉积的特征,揭示长爪沙鼠脂肪肝易感的分子机制、主要的调控靶点和网络作用特征,为临床治疗及新药研发提供一种背景相对清晰,耗时短的新型脂肪肝动物模型,同时也为NAFLD发病机制及药效新靶点的研究提供实验动物支撑,为选育近交系NAFLD长爪沙鼠奠定了理论与实践基础。     

Hepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.     

Treatment of atherogenic liver based on the pathogenesis of nonalcoholic fatty liver disease: a novel approach to reduce cardiovascular risk?

Nonalcoholic fatty liver disease (NAFLD), which spans a spectrum of conditions ranging from simple steatosis to progressive nonalcoholic steatohepatitis (NASH), is the most common chronic liver disease and a relevant public health issue. The prevalence of NAFLD depends on adiposity, age, gender and ethnicity. The natural history of liver disease in those with NAFLD critically depends on liver histological changes. However, cardiovascular mortality is increased in NAFLD, particularly in middle-aged adults. Against such a background, this review consists of three sections. First, data on NAFLD as a novel mechanism of increased cardiovascular risk via hyperinsulinism, pro-thrombotic potential, and subclinical inflammation are summarized. Next, the role of atherogenic liver in the development of manifestations of oxidative stress and atherosclerosis is emphasized. Finally, whether and how treating NAFLD will mechanistically result in reduced cardiovascular risk through ameliorated metabolic syndrome is discussed.     

Management of nonalcoholic fatty liver disease: a 60-year-old man with probable nonalcoholic fatty liver disease: weight reduction, liver biopsy, or both?

Nonalcoholic fatty liver disease (NAFLD) is one of the most common hepatic disorders in the United States, but uncertainty remains as to the optimal way to manage it. Using the case of Mr T, a 60-year-old man with obesity, diabetes mellitus, and increased serum transaminase levels, an evidence-based approach to diagnosis and treatment is discussed. Diagnosis of NAFLD is based on patient clinical profile and risk factors for metabolic syndrome, the exclusion of other liver diseases, radiologic imaging and sometimes biopsy. At this point in Mr T's disease, the most important step is differentiation between simple steatosis and nonalcoholic steatohepatitis (NASH). Simple steatosis has a benign natural history, but NASH is progressive and may lead to cirrhosis, liver failure, and liver cancer. An evidence-based approach to treatment is limited by lack of large randomized trials, particularly of combinations of therapies, but weight loss, exercise, and medical therapies targeted at the mechanism of liver injury in NASH are recommended. Improved noninvasive diagnostic tests, a clearer understanding of the natural history of NAFLD, and large, well-designed clinical trials are needed.     

病理学诊断的非酒精性脂肪性肝病患者的临床特点分析

目的:分析病理学诊断的非酒精性脂肪性肝病(nonalcoholic simple fatty liver disease,NAFLD)不同质谱的患者临床特点。方法:回顾性分析第四军医大学西京医院2000年至2012年肝移植供肝或肝穿刺、手术切除标本等来源的病理切片报告,根据患者病理诊断及临床资料分为正常组、单纯性脂肪肝组、非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)组、NASH-肝纤维化组、NASH-肝癌(hepatocelular carcinoma,HCC)组,共5组,回顾性分析数据完整的患者临床资料。结果:共纳入正常组20例,单纯脂肪肝组20例,NASH组14例,NASH-肝纤维化组8例,NASH-HCC组8例。结果表明,随着NAFLD疾病谱的进展,各组发生了相应代谢异常和肝脏转氨酶指标的改变。其中,NASH-肝纤维化组(69.2±4.2)岁与NASH-HCC组(71.4±6.4)岁的年龄较其他3组明显增高(P<0.05);NASH组年龄与单纯性脂肪肝组相比并无显著差异,但表现出更高的转氨酶水平和糖脂代谢紊乱的标志,例如甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-c)明显增加、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-c)显著降低;谷丙转氨酶(alanine aminotrans,ALT)、谷草转氨酶(aspartate transaminase,AST)以及r-谷氨酰转移酶(glutamyltranspeptidase,GGT)明显增加,其中以ALT增加最为显著,NASH组的ALT水平甚至超过了NASH-肝纤维化组和NASH-HCC组;NASH组代谢综合征(metabolic syndrome,MS)的比例达到了62%。结论:NASH是NAFLD发生过程中的重要病变和进展,此时代谢紊乱加重伴有肝细胞的炎症反应和损伤,胰岛素抵抗可能是NASH的重要发病机制。     

Development of a novel machine learning model to predict presence of nonalcoholic steatohepatitis

ObjectiveTo develop a computer model to predict patients with nonalcoholic steatohepatitis (NASH) using machine learning (ML).Materials and MethodsThis retrospective study utilized two databases: a) the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) nonalcoholic fatty liver disease (NAFLD) adult database (2004-2009), and b) the Optum^® de-identified Electronic Health Record dataset (2007-2018), a real-world dataset representative of common electronic health records in the United States. We developed an ML model to predict NASH, using confirmed NASH and non-NASH based on liver histology results in the NIDDK dataset to train the model.ResultsModels were trained and tested on NIDDK NAFLD data (704 patients) and the best-performing models evaluated on Optum data (~3,000,000 patients). An eXtreme Gradient Boosting model (XGBoost) consisting of 14 features exhibited high performance as measured by area under the curve (0.82), sensitivity (81%), and precision (81%) in predicting NASH. Slightly reduced performance was observed with an abbreviated feature set of 5 variables (0.79, 80%, 80%, respectively). The full model demonstrated good performance (AUC 0.76) to predict NASH in Optum data.DiscussionThe proposed model, named NASHmap, is the first ML model developed with confirmed NASH and non-NASH cases as determined through liver biopsy and validated on a large, real-world patient dataset. Both the 14 and 5-feature versions exhibit high performance.ConclusionThe NASHmap model is a convenient and high performing tool that could be used to identify patients likely to have NASH in clinical settings, allowing better patient management and optimal allocation of clinical resources.     

非酒精性脂肪肝影像诊断研究进展

非酒精性脂肪肝目前是成人及儿童慢性肝病最常见的原因,其发病率正在逐年上升。以非酒精性脂肪肝、非酒精性脂肪肝炎及脂肪性肝硬化的疾病谱强烈危害到人类的生命健康及寿命,且非酒精性脂肪肝已被指出与多种慢性疾病相关。正确意识并诊断该病已成为临床所需要重视的问题,但目前该病的诊断金标准仍为穿刺病理活检,影像学检查因其无创、重复性强等优点而利于患者的诊断及随访观察。就超声、CT及磁共振技术定性定量诊断非酒精性脂肪的研究进展予以阐述。     

非酒精性脂肪性肝病发病机制及治疗进展

非酒精性脂肪性肝病(NAFLD)是代谢综合征在肝脏的组成部分,是全球范围内广泛流行的慢性肝病。胰岛素抵抗(IR)可引起肝脏糖脂代谢紊乱,导致脂肪变。脂肪因子和炎性因子相互作用可导致IR,引起脂肪肝炎性改变,使NAFLD患者进展为非酒精性脂肪性肝炎(NASH)、肝纤维化甚至肝细胞癌。鉴于此,胰岛素增敏剂二甲双胍及噻唑烷二酮类药物能有效地治疗NAFLD。该文就NAFLD的发病机制与胰岛素增敏剂抗病机制及疗效予以综述。