减肥药用于非酒精性脂肪性肝病治疗的评价

非酒精性脂肪性肝病(NAFLD)是一种临床综合征,其肝组织学改变与酒精性肝病相类似但患者并无过量饮酒史.NAFLD患者通常合并肥胖症,而肥胖又可加重NAFLD的病情,甚至导致肝功能衰竭等终末期肝病.NAFLD患者肝细胞内过量脂肪沉积可能涉及多种机制,部分临床研究及动物试验显示,肥胖可致内脏脂肪组织功能失调、异常细胞因子表达及内源性大麻素系统相关的免疫紊乱等.近来研究提示,减轻体重有益于NAFLD的治疗.本文主要介绍并评价减肥药在NAFLD治疗中的作用,包括奥利司他、西布曲明及利莫那班等.     

非酒精性脂肪肝对药动学影响研究进展

非酒精性脂肪肝（NAFLD）是一种最常见的慢性肝病,严重威胁人类健康。在影响药物代谢的各种因素中,慢性肝病所起的作用最重要,可导致肝脏基因表达、mRNA及蛋白表达改变。非酒精性脂肪肝动物模型和非酒精性脂肪肝炎患者的研究结果显示,非酒精性脂肪肝时药物代谢酶及药物转运体发生显著改变。药物代谢酶和药物转运体在药物代谢过程中发挥重要作用,其改变可能影响药物在体内的清除,导致诸多临床药物的疗效、毒副作用甚至药物相互作用的发生。随着非酒精性脂肪肝的流行,越来越多的药物用于非酒精性脂肪肝患者。因此本文就非酒精性脂肪肝对药动学影响的研究进展作一综述。     

保肝抗炎药物在非酒精性脂肪性肝病治疗中的作用

非酒精性脂肪性肝病(NAFLD)的早期干预已获得大多数学者认同.保肝抗炎药物包括多烯磷脂酰胆碱、维生素E、水飞蓟素、熊去氧胆酸、甘草酸制剂和己酮可可碱等,是NAFLD综合治疗的重要组成部分.本文重点综述保肝抗炎药物的适用人群及常用药物的选用.多项临床研究提示,保肝抗炎药物町改善NAFLD患者的临床症状和血清氨基转移酶水平,但大多数保肝抗炎药物对肝脏纤维化进程的改善依据尚不足.     

脂肪细胞因子与非酒精性脂肪肝病

非酒精性脂肪肝病是发病率仅次于病毒性肝炎的常见肝病,是隐原性肝硬化的主要危险因素之一。多种脂肪细胞因子参与了脂肪肝的病理过程。本文就脂联素、瘦素、抵抗素、内脏脂肪素、Apelin、肠凝集素、网膜素等7种脂肪细胞因子与非酒精性脂肪肝的关系研究进展作一综述。     

胰岛素增敏剂在非酒精性脂肪性肝病中的应用

近年我国非酒精性脂肪性肝病(NAFLD)的患病率逐渐增高,胰岛素抵抗在NAFLD发病机制中具有重要作用,胰岛素增敏剂如噻唑烷二酮类药物和二甲双胍等逐渐成为NAFLD治疗药物的研究重点.本文综述近年NAFLD的临床治疗研究,评价胰岛素增敏剂在NAFLD治疗中的作用.     

非酒精性脂肪性肝病中MMP-9作用的研究进展

非酒精性脂肪性肝病（NAFLD）的发病受到多环节多因素调控,目前临床上尚无公认的特效治疗手段。因此,探索NAFLD的发病机制,发现其特异的治疗措施,对延缓病程进展、改善患者预后具有重要的临床意义。最新研究发现MMP 9可能在NAFLD进展过程中起了重要作用。本文就NAFLD发病过程中MMP 9作用的机制和相关研究做一综述。     

Herbal drug discovery for the treatment of nonalcoholic fatty liver disease

Few medications are available for meeting the increasing disease burden of nonalcoholic fatty liver disease (NAFLD) and its progressive stage, nonalcoholic steatohepatitis (NASH). Traditional herbal medicines (THM) have been used for centuries to treat indigenous people with various symptoms but without clarified modern-defined disease types and mechanisms. In modern times, NAFLD was defined as a common chronic disease leading to more studies to understand NAFLD/NASH pathology and progression. THM have garnered increased attention for providing therapeutic candidates for treating NAFLD. In this review, a new model called “multiple organs-multiple hits” is proposed to explain mechanisms of NASH progression. Against this proposed model, the effects and mechanisms of the frequently-studied THM-yielded single anti-NAFLD drug candidates and multiple herb medicines are reviewed, among which silymarin and berberine are already under U.S. FDA-sanctioned phase 4 clinical studies. Furthermore, experimental designs for anti-NAFLD drug discovery from THM in treating NAFLD are discussed. The opportunities and challenges of reverse pharmacology and reverse pharmacokinetic concepts-guided strategies for THM modernization and its global recognition to treat NAFLD are highlighted. Increasing mechanistic evidence is being generated to support the beneficial role of THM in treating NAFLD and anti-NAFLD drug discovery.     

罗格列酮治疗非酒精性脂肪肝的临床效果观

目的观察罗格列酮治疗非酒精性脂肪肝（NAFLD）的临床效果。方法将100例NAFLD患者完全随机的方法分为观察组和对照组,各50例。观察组口服罗格列酮4 mg,1次/d;对照组口服二甲双胍片0.5 g,3次/d;2组疗程均为6个月。观察2组治疗前后体重指数、肝功能［丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、谷氨酰转肽酶（GGT）］、血脂（总胆固醇、三酰甘油）、胰岛素抵抗指数（HOMA IR）及空腹胰岛素（FINS）水平的变化。结果观察组总有效率为84.0%（42/50）,对照组总有效率为66.0%（33/50）,2组比较差异有统计学意义（P＜0.05）。观察组治疗后体重指数、肝功能（ALT、AST、GGT）、血脂（总胆固醇、三酰甘油）、HOMA IR及FINS水平较治疗前明显改善［（22±7）kg/m2比（28±9）kg/m2;（36±7）U/L比（116±9）U/L,（29±7）U/L比（97±8）U/L,（27±6）U/L比（75±8）U/L;（4.0±1.1）mmol/L比（5.0±1.3）mmol/L,（1.3±0.7）mmol/L比（2.6±1.3）mmol/L;（9±4）mU/L比 （13±9）mU/L,（1.6±1.1）×103比（2.6±1.2）×103］（P＜0.05）,与对照组治疗后［分别为（25±7）kg/m2,（71±9）U/L,（66±3）U/L,（62±6）U/L,（3.6±1.7）mmol/L,（1.8±0.7）mmol/L,（11±3）mU/L,（2.1±1.4）×103］比较,差异均有统计学意义（均P＜0.05）。结论罗格列酮能够治疗NAFLD,通过改善靶组织对胰岛素的敏感性,改善NAFLD的胰岛素抵抗,调节血脂,从而减轻NAFLD的肝损害,疗效优于二甲双胍。     

非酒精性脂肪性肝病的药物治疗

<正>由于缺少有组织学终点以及远期并发症和死亡转归的随机对照研究,药物对非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的治疗效     

天然免疫与非酒精性脂肪肝病

肝脏中大量的巨噬细胞、自然杀伤细胞(natural killer,NK)、自然杀伤T细胞(natural killer T cell,NKT)等构成了天然免疫系统.这一系统细胞功能紊乱,发生Th-1极化,使促炎症因子产生增多,促进了非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)的形成;肝脏持续的暴露于这些炎症因子,可以促进多种促纤维化因子产生,但Th-2细胞因子分泌的不足, 使NASH进一步发展为肝硬化的现象却相对比较少见.本文就肝脏天然免疫系统在非酒精性脂肪肝病(nonalcoholic fatty liver disease, NAFLD)中的调节机制作一综述.     

非酒精性脂肪性肝病的综合治疗

非酒精性脂肪性肝病(NAFLD)是代谢综合征在肝脏的表现,其疾病谱包括非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)和肝硬化.其治疗应为综合性下预,包括通过调整生活方式、药物及手术治疗等方法改善胰岛素抵抗,减少易致肝脏损伤的因素,必要时可应用保肝抗炎药物,终末期NAFLD患者需行肝移植术.     

Current pharmacological treatment of nonalcoholic fatty liver

Nonalcoholic fatty liver disease (NAFLD) is a frequent and potentially progressive chronic liver disease that occurs in subjects who do not abuse alcohol. NAFLD is often associated with obesity, metabolic syndrome and insulin resistance and its more aggressive form, nonalcoholic steatohepatitis (NASH) is a major cause of cryptogenic cirrhosis. NAFLD/NASH are commonly detected because of elevated serum aminotransferase levels, ultrasonographic fatty liver and, at liver histology, steatosis, inflammation, and occasionally fibrosis that may progress to cirrhosis. No established treatment exists for this potentially serious disorder. Current management of NAFLD/NASH is largely conservative and includes diet regimen, aerobic exercise, and interventions towards the associated metabolic abnormalities. The main concern is therefore to decrease liver steatosis and its progression toward steatohepatitis and fibrosis, and the risk of cryptogenic cirrhosis. Among the most promising medications, weight reducing drugs, insulin sensitizers and lipid-lowering agents, antioxidants, bile salts, co-factors increasing the mitochondrial transport of fatty acids are being considered. Among them, thiazolidinediones are the most promising drug family that act by activating PPARgamma nuclear receptors and by regulating both microsomal and peroxisomal lipid oxidative pathways. Pharmacological treatment of obesity and probiotics should be considered as potential therapeutic options. In this review, after summarizing the general background on fatty liver, the most current and attractive pharmacological approaches to the problem of NAFLD/NASH are discussed.     

Current therapies for nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in adults and children in many regions of the world. Although a relatively benign condition in some, for others the disease will progress to cirrhosis and end-stage liver disease with associated complications including hepatocellular cancer. Pharmaceutical therapies have had mixed results and none are accepted as standard therapy. Depending on the metric used to assess response (biochemical or histological), there are some therapies which may afford benefit. Others, however, have caused less than desirable adverse effects. Unfortunately, no particular treatment has emerged as safe and highly effective. The cornerstones of management of this problematic condition should include exercise and efforts at weight reduction through dietary changes and increased physical activity. Weight reduction does indeed seem to be beneficial in this setting, as evidenced by studies including those evaluating the effect of bariatric surgery. Less is known, however, about the effort of exercise in and of itself as a treatment strategy, even in the absence of a reduction in body weight. In this paper, we review the literature pertaining to the current state of NAFLD management with an emphasis on pharmacotherapy.     

Drug metabolism alterations in nonalcoholic fatty liver disease

Drug-metabolizing enzymes play a vital role in the elimination of the majority of therapeutic drugs. The major organ involved in drug metabolism is the liver. Chronic liver diseases have been identified as a potential source of significant interindividual variation in metabolism. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting between 60 and 90 million Americans, yet the vast majority of NAFLD patients are undiagnosed. NAFLD encompasses a spectrum of pathologies, ranging from steatosis to nonalcoholic steatohepatitis and fibrosis. Numerous animal studies have investigated the effects of NAFLD on hepatic gene expression, observing significant alterations in mRNA, protein, and activity levels. Information on the effects of NAFLD in human patients is limited, though several significant investigations have recently been published. Significant alterations in the activity of drug-metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions. With the enormous prevalence of NAFLD, it is conceivable that every drug currently on the market is being given to patients with NAFLD. The current review is intended to present the results from both animal models and human patients, summarizing the observed alterations in the expression and activity of the phase I and II drug-metabolizing enzymes.     

GI epidemiology: nonalcoholic fatty liver disease

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common diagnosis in clinical practice. Insulin resistance and oxidative stress play an important role in NAFLD development and progression. AIM: To review the data available on the epidemiology and natural history of NAFLD as well as the risk factors for its development and the areas where future research is necessary. RESULTS /CONCLUSIONS: NAFLD may affect individuals of any age range and race/ethnicity. NAFLD affects one in three adults and one in ten children/adolescents in the United States. Mortality in patients with NAFLD is significantly higher than in the general population of same age and gender with liver-related complications being a common cause of death. Liver-related morbidity and mortality in NAFLD occurs when the disease has progressed to advanced fibrosis and cirrhosis. Further studies are necessary to determine the impact of NAFLD on health-related quality of life and resources utilization, and to the extent to which preventing the development of the metabolic syndrome would prevent NAFLD development and reduce liver-related morbidity and mortality. Lifestyle intervention may improve NAFLD, but medications that increase insulin sensitivity and the antioxidant defenses in the liver deserve evaluation in carefully controlled trials.     

利拉鲁肽治疗非酒精性脂肪性肝病的作用机制及研究进展

非酒精性脂肪性肝病（NAFLD）是我国最常见的慢性肝脏疾病之一。大多数病人的肝脂肪变性的发展与饮食中的脂肪摄入有关,其特征为自由脂肪酸摄入增加和肝脏脂肪重新生成,肝细胞中三酰甘油过度积聚。非酒精性脂肪性肝炎是一种由单纯性肝脂肪性变进展为肝细胞死亡、炎症浸润和纤维化状态的代谢性肝病,是NAFLD较严重的状态,是肝硬化、肝癌的重要危险因素。胰高血糖素样肽-1(GLP-1)是回肠内分泌细胞分泌的一种脑肠肽,进餐后血糖升高刺激胰高血糖素样肽-1分泌,抑制α细胞分泌胰高血糖素,防止餐后高血糖。以往的研究中,GLP-1受体激动剂被明确批准用于治疗糖尿病和肥胖症。其中,GLP-1受体激动剂利拉鲁肽除了其降血糖效果外,还对NAFLD存在有益的影响。该文对利拉鲁肽在NAFLD中的作用及机制研究进展做一综述。     

复方中药治疗非酒精性脂肪性肝病的实验研究

目的观察复方中药治疗非酒精性脂肪性肝病的疗效和作用机制。方法运用高脂饲料饮食制备非酒精性脂肪性肝病动物模型,治疗组药物灌胃,采用酶法测定血及肝组织中总胆固醇(TC)、甘油三酯(TG)、游离脂肪酸(FFA)及血中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)的含量,观察肝组织学变化。采用反转录-聚合酶链反应(RT-PCR)测定酰基辅酶A氧化酶(AOX)的表达。结果中药高剂量组血及肝中TC、TG、FFA含量较模型组有明显降低(P<0.05);中药高剂量组ALT、AST较模型组有明显降低(P<0.05);中药治疗组肝组织脂肪变及炎症计分较模型组有明显降低(P<0.05);AOX的表达中药组和吉非贝齐组较模型组明显升高(P<0.05)。结论中药治疗非酒精性脂肪性肝病有明显疗效,可能通过激活过氧化物酶体增生物激活受体-α(PPAR-α)使AOX表达上调而改善脂肪变。     

调脂药物在非酒精性脂肪性肝病中的应用

非酒精性脂肪性肝病(NAFLD)是以弥漫性肝细胞大泡性脂肪变性为主要特征,且患者并无过量饮酒史的临床综合征,其基础治疗目前仍以饮食控制及运动为主:合并高脂血症的NAFLD患者,改变生活方式和(或)接受降糖或减轻体重药物治疗3～6月以上仍有混合性高脂血症或高脂血症合并2个以上心血管危险因素者,加用他汀类、贝特类或普罗布考等调脂药物,可延缓患者动脉粥样硬化进程,减少心脑血管事件的发生.本文简要综述调脂药物在NAFLD中的应用.     

Novel therapeutic targets for nonalcoholic fatty liver disease

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a serious public health problem. It is now estimated to affect 30% of adults and about 10% of children in the U.S. Hispanics are disproportionably affected with not only higher rates of NAFLD but also more severe disease. Treatment options are currently limited.

Areas covered: In this review, we will focus on a series of novel findings related to the pathobiology of liver damage in nonalcoholic steatohepatitis (NASH) that are attractive targets for development of novel therapeutic strategies for human NASH. In particular, we will discuss four different areas due to their novelty and growing importance including microparticles, the inflammasomes, gut-liver axis and dietary lipids.

Expert opinion: There is an urgent need to develop novel safe and effective therapies for the growing NAFLD epidemic. The data discussed in this article provide strong rational to think out of the box when considering novel therapeutic targets for patients with NAFLD.