还原型谷胱甘肽配合藿朴夏苓汤加味治疗非酒精性脂肪肝疗效观察

非酒精性脂肪肝（ non-alcoholic fatty liver disease ,NAFLD）是指除外酒精和其他明确损肝因素所致的临床病理综合征,肝细胞内脂肪过度沉积为其主要特征［1］。 NAFLD包括单纯性脂肪肝、非酒精性脂肪性肝炎（ NASH）和其相关肝硬化。随着饮食结构和生活习惯的改变,NAFLD的发病率逐渐上升,已成为我国常见的慢性肝病之一。目前尚未发现疗效确切的药物,常用保肝药物进行辅助治疗。中医药治疗脂肪肝具有疗效稳定持久、不良反应少等优点。我院采用还原型谷胱甘肽片配合藿朴夏苓汤加味治疗NAFLD,报告如下。     

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。     

脂肪性肝炎的药物治疗进展

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,包括单纯性非酒精性脂肪肝（NAFL）以及由其演变的脂肪性肝炎（NASH）和肝硬化。本文就近年来有关NASH药物治疗的临床研究综述如下。     

荷丹片联合二甲双胍治疗非酒精性脂肪肝伴代谢综合征的疗效观察

非酒精性脂肪性肝病（NAFLD）是一种常见慢性肝病,研究表明,NAFLD与代谢综合征（MS）密切相关。本研究应用荷丹片联合二甲双胍治疗NAFLD伴MS患者,观察其对脂肪肝及糖脂代谢等影响。     

肠道微生态和脂肪性肝病

脂肪性肝病包括酒精性肝病（alcoholic liver disease, ALD）和非酒精性脂肪性肝病（nonalcoholic fatty liver disease, NAFLD）.随着生活方式的改变，脂肪性肝病目前已成为除病毒性肝炎以外最常见的肝病。ALD的病因为过量饮酒，而NAFLD则主要与肥胖、糖尿病、高脂血症等代谢紊乱相关。无论ALD或NAFLD．都包括三个逐渐进展的病理阶段：脂肪肝、脂肪性肝炎、肝硬化。     

非酒精性脂肪性肝病诊疗指南

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脂肪性肝炎（NASH）和肝硬化．胰岛素抵抗和遗传易感性与其发病关系密切。随着肥胖和糖尿病的发病率增加，NAFLD现已成为我国常见的慢性肝病之一，严重危害人民健康。为进一步规范NAFLD的诊断、治疗和疗效评估，中华医学会肝病学分会脂肪肝和酒精性肝病学组组织国内有关专家．在参考国内外最新研究成果的基础上，按照循证医学的原则，制定了《非酒精性脂肪性肝病诊疗指南》（以下简称《指南》）（2006年2月修订）。其中推荐的意见所依据的证据共分为3个级别5个等次，文中以括号内斜体罗马数字表示，推荐意见的证据分级，参见《酒精性肝病诊疗指南》表1。     

非酒精性脂肪性肝病的自然史

不同阶段的非酒精性脂肪性肝病（NAFLD）患者自然史有较大不同．现分别介绍非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎（NASH）及NASH相关肝硬化的自然史。     

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。     

甲硫氨酸治疗非酒精性脂肪肝45例疗效分析

非酒精性脂肪性肝病（nonalcoholic fatty liverdisease，NAFLD）是除外酒精和其他明确的肝损因素所致的，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他演变的脂肪性肝炎和肝硬化，胰岛素抵抗和遗传易感性与其发病关系密切。随着临床诊断技术的不断完善，脂肪肝的检出率逐年增高，目前对其尚缺乏特效的药物治疗。2006年4月至2007年12月，我院采用甲硫氨酸治疗NAFLD患者45例，取得较好疗效，现报告如下。     

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。     

Changes in drug transport and metabolism and their clinical implications in non-alcoholic fatty liver disease

Introduction: The incidence of non-alcoholic fatty liver disease (NAFLD) is rising, especially in Western countries. Drug treatment in patients with NAFLD is common since it is linked to other conditions like diabetes, obesity, and cardiovascular disease. Consequently, changes in drug metabolism may have serious clinical implications.

Areas covered: A literature search for studies in animal models or patients with obesity, fatty liver, non-alcoholic steatohepatitis (NASH) or NASH cirrhosis published before November 2016 was performed. After discussing epidemiology and animal models for NAFLD, we summarized both basic as well as clinical studies investigating changes in drug transport and metabolism in NAFLD. Important drug groups were assessed separately with emphasis on clinical implications for drug treatment in patients with NAFLD.

Expert opinion: Given the frequency of NAFLD even today, a high degree of drug treatment in NAFLD patients appears safe and well-tolerated despite considerable changes in hepatic uptake, distribution, metabolism and transport of drugs in these patients. NASH causes changes in biliary excretion, systemic concentrations, and renal handling of drugs leading to alterations in drug efficacy or toxicity under specific circumstances. Future clinical drug studies should focus on this special patient population in order to avoid serious adverse events in NAFLD patients.     

非酒精性脂肪性肝病联合用药临床研究进展

非酒精性脂肪性肝病（NAFLD）是临床上最常见的慢性肝病,全球发病率约为25%,NAFLD可进展为肝纤维化、肝硬化和肝细胞癌,严重威胁人类健康。目前我国尚未批准任何治疗药物上市,新药研发迫在眉睫。NAFLD发病机制复杂,单一用药很难取得好的疗效。几种不同作用机制的药物联合使用是未来治疗NAFLD的必然趋势。通过联合用药可能降低药物的不良反应,发挥协同作用产生更好的疗效。本文综述了NAFLD联合用药的最新临床研究进展,以期为后续NAFLD新药开发和临床合理用药提供参考。     

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.     

非酒精性脂肪性肝病治疗药物的应用评价

非酒精性脂肪性肝病（NAFLD）是目前最常见的肝脏疾病之一,其药物治疗目的主要是减缓或减少肝硬化、肝癌及肝衰竭等终末期肝病的发生,降低病死率。本文综述近年来胰岛素增敏剂、降脂药、抗氧化剂和肝细胞保护剂等各种NAFLD药物治疗方案的临床应用评价。     

炎症小体介导的细胞焦亡在非酒精性脂肪肝病中的作用及机制

非酒精性脂肪肝病包含单纯性脂肪肝、非酒精性脂肪肝炎和肝硬化等一系列病变,是造成肝硬化、肝细胞癌症的主要因素和肝脏器官移植的重要诱因。非酒精性脂肪肝的发病机制尚不明确,除了加强运动、改善饮食习惯外,目前尚无公认有效的药物治疗方式。细胞焦亡是一种新发现的程序性细胞死亡方式,依赖于天冬氨酸特异性半胱氨酸蛋白酶1（caspase-1）或caspase-11等介导的炎性小体的激活。细胞焦亡过程中常伴有炎症反应的发生,而炎症小体则是细胞产生焦亡和炎症反应所必需的多聚体蛋白复合物,其主要功能是活化caspase-1,从而间接调控炎症因子白介素1（IL-1）和IL-18的表达和分泌。最近的研究表明,细胞焦亡和炎症小体在非酒精性脂肪肝病的发生发展中起重要作用。针对该领域的最新研究进行综述,以期为非酒精性脂肪肝的防治提供新的科学认识和信息。     

Hyperuricaemia and non-alcoholic fatty liver disease (NAFLD): a relationship with implications for vascular risk?

Both elevated levels of uric acid and non-alcoholic fatty liver disease (NAFLD) have been associated with increased vascular risk. Furthermore, certain drugs (e.g. lipid and blood pressure lowering) that decrease)cardiovascular risk and improve/preserve renal function were shown to influence serum uric acid (SUA) levels and/or NAFLD. A link between hyperuricaemia and NAFLD has also been suggested. This review considers the associations between hyperuricaemia, NAFLD and vascular risk. We also discuss the effects of different drug treatments on SUA and NAFLD. As NAFLD is a very common condition, future work in this field is needed with regard to a more practical definitive diagnosis, evidence- based treatments and a better understanding of the possible links between NAFLD, elevated SUA levels, cardiovascular disease and chronic kidney disease. Whether treating hyperuricaemia and NAFLD will translate into a reduced risk of vascular events requires further investigation.     

The pharmacological management of NAFLD in children and adolescents

Introduction: Non-alcoholic fatty liver disease (NAFLD) represents a spectrum, including ‘simple’ steatosis, non-alcoholic steatohepatitis (NASH), and fibrosis. Increasing prevalence of NAFLD has followed the international rise in obesity and lifestyle modification is the mainstay therapy for children. To date, pharmacological trials have had varying efficacy but a large number of new agents are in early phase trials for adults.

Areas covered: This review explores the effect of current and potential future paediatric NAFLD treatments in terms of histological and biochemical endpoints. The potential for the extension of adult treatments to children is discussed, as well as what limits the use of certain agents in children.

Expert commentary: No drugs have yet to be licenced for NAFLD. Trial heterogeneity makes comparison of drugs between studies challenging. FXR agonists are yet to be trialled in children but may represent a safe and potentially efficacious therapy. Future treatments would likely encompass a multimodal approach that may include bariatric surgery.     

Variations in ATP-binding cassette transporter regulation during the progression of human nonalcoholic fatty liver disease

Transporters located on the sinusoidal and canalicular membranes of hepatocytes regulate the efflux of drugs and metabolites into blood and bile, respectively. Changes in the expression or function of these transporters during liver disease may lead to a greater risk of adverse drug reactions. Nonalcoholic fatty liver disease (NAFLD) is a progressive condition encompassing the relatively benign steatosis and the more severe, inflammatory state of nonalcoholic steatohepatitis (NASH). Here, we present an analysis of the effect of NAFLD progression on the major ATP-binding cassette (ABC) efflux transport proteins ABCC1-6, ABCB1, and ABCG2. Human liver samples diagnosed as normal, steatotic, NASH (fatty), and NASH (not fatty) were analyzed. Increasing trends in mRNA expression of ABCC1, ABCC4-5, ABCB1, and ABCG2 were found with NAFLD progression, whereas protein levels of all transporters exhibited increasing trends with disease progression. Immunohistochemical staining of ABCC3, ABCB1, and ABCG2 revealed no alterations in cellular localization during NAFLD progression. ABCC2 staining revealed an alternative mechanism of regulation in NASH in which the transporter appears to be internalized away from the canalicular membrane. This correlated with a preferential shift in the molecular mass of ABCC2 from 200 to 180 kDa in NASH, which has been shown to be associated with a loss of glycosylation and internalization of the protein. These data demonstrate increased expression of multiple efflux transporters as well as altered cellular localization of ABCC2 in NASH, which may have profound effects on the ability of patients with NASH to eliminate drugs in an appropriate manner.