肝脏非实质细胞在非酒精性脂肪性肝炎中的作用研究进展

非酒精性脂肪性肝病是全球最流行的肝脏疾病,其疾病谱包含非酒精性脂肪肝、非酒精性脂肪性肝炎、与非酒精性脂肪性肝炎相关的纤维化、肝硬化和肝细胞癌。非酒精性脂肪性肝炎是非酒精性脂肪性肝病进展性的肝脏病理表征,临床上需要药物治疗或其他治疗方式干预,但目前全球尚无针对非酒精性脂肪性肝炎的药物获批上市。非酒精性脂肪性肝炎发病机制复杂,涉及多种细胞内、细胞间的交互作用以及复杂的分子信号通路。非酒精性脂肪性肝炎治疗是一个尚未被满足的巨大临床需求。综述了肝脏中几种主要的非实质细胞在非酒精性脂肪性肝炎发病中的重要作用,同时探讨了非酒精性脂肪性肝炎药物开发靶点与不同细胞之间的相关性。     

非酒精性脂肪性肝炎内科综合治疗临床观察

随着生活水平的提高,脂肪肝尤其是非酒精性脂肪性肝病日益增加,非酒精性脂肪性肝炎是非酒精性脂肪性肝病中的一种临床类型。我们探讨内科综合治疗对非酒精性脂肪性肝炎的疗效。1资料与方法1.1一般资料2006年3月至2007年6月消化科就诊的非酒精性脂肪性肝炎患者,将患者采取随机编     

非酒精性脂肪性肝病不容忽视

非酒精性脂肪性肝病是一种与胰岛素抵抗及遗传等密切相关的代谢应激性肝脏损伤,其病理学改变与酒精性肝病相似,但患者无过量饮酒史。非酒精性脂肪性肝病包括：非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎及其相关肝硬化和肝细胞癌。     

非酒精性脂肪性肝炎诊断研究进展

非酒精性脂肪性肝病是一种慢性非传染性疾病。近年来其患病率和发病率不断增高,发病年龄也出现低年龄化趋势,该疾病已取代慢性乙型肝炎成为第一大慢性肝脏疾病。重点综述非酒精性脂肪性肝病中的非酒精性脂肪性肝炎的诊断研究进展,介绍非酒精性脂肪性肝炎的临床病史、病理学诊断、非侵入方法诊断,为临床诊断提供参考。     

非酒精性脂肪性肝病的诊断

非酒精性脂肪性肝炎（NASH）是指病理上与酒精性肝炎相类似但无过量饮酒史的临床综合征，患者通常存在胰岛素抵抗及其相关代谢紊乱。当代谢性肝病的病理学特征不明或泛指整个脂肪性肝病的疾病谱时，通常使用非酒精性脂肪性肝病（NAFLD）这一术语，后者尚包括单纯性肝脂肪变或伴小叶内炎症，但没有肝细胞气球样变和纤维化，或仅伴孤立性门脉周围纤维化，以及无明显脂肪性肝炎的隐源性肝硬化等情况。随着社会经济的发展，NASH/NAFLD已成为重要的肝病之一，严重危害人类的健康。     

重度肥胖与非酒精性脂肪性肝病

非酒精性脂肪性肝病是发生于无明显饮酒的常见慢性肝病。包括单纯性脂肪肝、脂肪性肝炎、肝纤维化及肝硬化。研究证实，肥胖、糖尿病及高脂血症等是非酒精性脂肪性肝病形成的危险因素，其中肥胖是最重要的危险因素。而重度肥胖与非酒精性脂肪性肝病关系更密切。     

非酒精性脂肪性肝病的药物治疗进展

随着生活水平的不断提高，脂肪性肝病已成为常见病和多发病，尤其是非酒精性脂肪性肝病的患病率日益增加，趋于超过病毒性肝炎和酒精性肝病，成为全球普遍关注的医学问题和社会问题。非酒精性脂肪性肝病（Non—alcoholic fatty liver disease，NAFLD）简称脂肪肝，是一类肝组织学改变与酒精性肝病类似但无过量饮酒史的临床病理综合征。其病理改变是以肝实质细胞脂肪变性和脂肪贮积为特征。     

非酒精性脂肪性肝病的治疗

非酒精性脂肪性肝病(BAFLD)又称非酒精性脂肪肝,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,包括单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)和脂肪性肝硬化,其中NASH不仅可使肝酶持续异常,而且可导致失代偿期肝硬化、肝细胞癌以及肝功能衰竭,目前已成为仅次于慢性病毒性肝炎、酒精性肝病的重要肝硬化前期病变之一。     

非酒精性脂肪性肝病与胰岛素抵抗关系及超敏C反应蛋白在其临床分型上作用

目的探讨非酒精性脂肪性肝病（NAFLD）患者胰岛素抵抗（IR）的关系及超敏c反应蛋白（hs—CRP）水平对非酒精性单纯性脂肪肝（NAFL）和非酒精性脂肪性肝炎（NASH）的鉴别诊断作用。方法随机选择符合非酒精性脂肪性肝病临床诊断标准的NAFLD患者132例,按临床分型标准分为NAFL组82例,NASH组50例;同时选择50例健康人为对照组。分别观察三组空腹血糖（FPG）、空腹胰岛素（FINS）及hs—CRP水平,并采用稳态模式评估法（HOMA）计算胰岛素抵抗指数（HOMA—IR）。结果①FINS与HOMA—IR在对照组与二组NAFLD之间比较差异有统计学意义（P〈0．01）,NAFLD与HOMA—IR呈正相关关系。②NASH组hs—CRP比NAFL组高,两者比较差异有非常显著性意义（P〈0．01）。结论①IR是NAFLD的独立危险因素,是非酒精性单纯脂肪肝的主要表现。②检测hs—CRP对非酒精性单纯脂肪肝和非酒精性脂肪性肝炎具有鉴别诊断的作用。     

非酒精性脂肪肝的诊疗现状及展望

<正>非酒精性脂肪肝(NAFL),又称非酒精性脂肪性肝病(NAFLD),是近来被广泛认识的慢性肝病,是一种无过量饮酒史、肝实质细胞脂肪变性和脂肪贮积为特征的临床病理综合征。非酒精性脂肪性肝炎(NASH)可逐渐进展为肝硬化、肝癌等终末期肝病,已成为目前仅次于慢性病毒性肝     

Promising therapies for treatment of nonalcoholic steatohepatitis

Introduction: Non-alcoholic fatty liver disease (NAFLD) has become the most common etiology for abnormal aminotransferase levels and chronic liver disease. Its growing prevalence is largely linked to the presence of metabolic syndrome, particularly diabetes and insulin resistance. It is estimated that 60–80% of the type 2 diabetic population has NAFLD. NAFLD encompasses a range of conditions ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). A subset of patients with hepatic steatosis progress to NASH, while 15–20% of patients with NASH develop cirrhosis. This progression is thought to be multifactorial, and there are currently no FDA-approved medications for the treatment of NASH.

Areas covered: We review drugs currently in Phase II and III clinical trials for treatment of NAFLD and NASH, including their mechanisms of action, relationship to the pathophysiology of NASH, and rationale for their development.

Expert opinion: The treatment of NASH is complex and necessitates targeting a number of different pathways. Combination therapy, preferably tailored toward the disease stage and severity, will be needed to achieve maximum therapeutic effect. With multiple agents currently being developed, there may soon be an ability to effectively slow or even reverse the disease process in many NAFLD/NASH patients.     

血清瘦素水平与非酒精性脂肪性肝病相关性研究

目的探讨非酒精性脂肪性肝病（NAFLD）患者血清瘦素（LEP）水平及其在“二次打击”发病机制中的作用。方法选择单纯NAFLD患者43例,非酒精性脂肪性肝炎（NASH）患者41例以及健康对照组40例,测定并比较空腹LEP水平。采用稳态胰岛素评价指数（HOMA）评价胰岛素抵抗程度,丙二醛（MDA）评价脂质过氧化程度,血清Ⅲ型前胶原肽（PCHI）、Ⅳ型胶原（IV-C）、层粘连蛋白（LN）、透明质酸（HA）作为肝纤维化指标。分析NAFLD患者中LEP与胰岛素抵抗及脂质过氧化程度、肝纤维化的关系。结果单纯NAFL组HOMA、LEP值高于对照组,单纯NAFL患者MDA、PCⅢ、Ⅳ-C、LN、HA与对照组比较差异无统计学意义,NASH患者HOMA、LEP、MDA、PCIII、1V-C、LN、HA明显高于对照组及单纯NAFL组,单纯NAFL及NASH患者LEP与HOMA值呈正相关,NASH患者LEP水平与MDA及肝纤维化血清学指标PCⅢ、IV—C、LN、HA呈正相关。结论LEP与NAFLD的发病机制有关,是“初次打击”胰岛素抵抗诱发脂肪肝的中介激素,LEP参与调节NAFLD的炎性反应,促使脂肪肝发展为脂肪性肝炎,LEP为NAFLD发病机制中“二次打击”（炎症．坏死循环）的致病因子之一;从而促进肝纤维化的发生。并可能是导致肝纤维化的始动因子之一。     

Present and future therapeutic strategies in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is found in individuals who do not drink or abuse alcohol and represents a significant health burden for the general community. NAFLD is often associated with one or more features of the metabolic syndrome and has potential for evolution towards non-alcoholic steatohepatitis (NASH), the necro-inflammatory form of liver steatosis. The most worrisome evolutive events in a subgroup of NASH patients include advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Pathophysiology of NAFLD/NASH is complex, but studies point to a pre-eminent role of oxidative stress and lipid peroxidation in the liver, including early mitochondrial dysfunction. Changes follow an insulin resistance status with a background of a chronic pro-inflammatory status due to an excess of visceral adiposity. Although no established therapy exists for NAFLD/NASH, potential therapeutic approaches are discussed in this review.     

Present and future therapeutic strategies in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is found in individuals who do not drink or abuse alcohol and represents a significant health burden for the general community. NAFLD is often associated with one or more features of the metabolic syndrome and has potential for evolution towards non-alcoholic steatohepatitis (NASH), the necro-inflammatory form of liver steatosis. The most worrisome evolutive events in a subgroup of NASH patients include advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Pathophysiology of NAFLD/NASH is complex, but studies point to a pre-eminent role of oxidative stress and lipid peroxidation in the liver, including early mitochondrial dysfunction. Changes follow an insulin resistance status with a background of a chronic pro-inflammatory status due to an excess of visceral adiposity. Although no established therapy exists for NAFLD/NASH, potential therapeutic approaches are discussed in this review.     

The natural history and risk factors for progression of non-alcoholic fatty liver disease and steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is a condition of increasing incidence in western Countries seldom associated to other diseases of high prevalence in general population (i.e. diabetes and obesity). NAFLD ranges from simple fatty liver to steatohepatitis (NASH), which may lead to cryptogenic cirrhosis and in some cases hepatocellular carcinoma (HCC). Natural history of NAFLD in humans is poorly understood and progression of liver disease seems to be due to interaction between hosting (i.e. genetic, gut flora, insulin resistance) and environmental factors (social and eating behaviours) that should be responsible of increased oxidative stress within hepatocytes. Even if we need non-invasive markers able to describe the progression of liver disease, only meaning of liver biopsy is useful to characterize the stigmata of worsening such as inflammation and fibrosis.     

非酒精性脂肪肝80例临床分析

目的探讨比较非酒精性单纯性脂肪肝（NAFL）与非酒精性脂肪性肝炎（NASH）的临床区别,以便于临床诊断与治疗。方法对经肝组织病理检查确诊的非酒精性脂肪肝（NAFLD）80例（单纯性脂肪肝40例,脂肪性肝炎40例）进行B超、肝功能、血脂、血清纤维化指标检测比较。结果 NASH患者在肝功能、血脂、血清纤维化指标上均较NAFL增高,两组比较有统计学差异（P〈0.05）。结论非酒精性脂肪肝能转化为脂肪性肝炎甚至肝硬化,尽早的确诊对预后及治疗有着积极的意义。     

非酒精性脂肪性肝病的治疗进展

目前全球非酒精性脂肪性肝病的发病率增加,并与代谢综合征,尤其是肥胖及糖尿病密切相关.越来越多的证据表明,胰岛素抵抗是代谢综合征患者发生脂肪性肝炎的关键病因,其可增加脂肪变性及肝脏游离脂肪酸聚集,刺激氧化应激反应,促进脂质过氧化及炎症细胞因子产生.非酒精性脂肪性肝病的治疗以改善代谢综合征为主,尚缺乏已验证的疗效理想的治疗药物.近年来随着对其发病机制的深入理解,一些尚处于动物试验及前期临床研究的新药值得关注.     

Non-alcoholic steatohepatitis: what can we learn from animal models?

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver function and correlates with central adiposity, obesity, insulin resistance, the metabolic syndrome and type 2 diabetes mellitus. The pathological spectrum of NAFLD ranges from fatty liver to non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and even hepatocellular carcinoma. Though NAFLD and NASH are becoming a major public health problem, ethical constraints on obtaining human liver tissue limit the interpretability of the data and the ability to delineate cause and effect from complex, interactive disease pathogenic pathways. Animal models of NASH can provide critical information leading to identify potential drug targets and to understand their molecular mechanisms, and are platforms for compound screening in drug development and for the assessment of novel therapeutic strategies. This review is aimed to offer an updated overview of the nutritional, genetic and pharmacologic animal models of NASH. Though the information derived from these models has clear relevance for the comprehension of the molecular basis of human disease, most of them fail to reproduce the full spectrum of liver pathology and the metabolic context that characterizes human NASH. Consequently, it is necessary to establish animal models that can best mimic the actual etiology, progression, and pathogenesis of the disease, and prove effectiveness for examining and selecting compounds with potential therapeutic benefit in NASH.