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1.
目的探讨非酒精性脂肪肝(NAFLD)的相关危险因素及防治。方法回顾性分析140例NAFLD住院患者的临床资料,总结与之相关的危险因素。结果男性NAFLD患病率相比女性患病率高,女性NAFLD患病率随年龄增长呈升高趋势。NAFLD危险因素主要有胰腺炎,胆道感染,肿瘤,糖尿病相关外周血管病变和年龄。结论 NAFLD形成的主要危险因素与多种疾病密切相关,伴发疾病是导致病情进展及死亡的重要因素,采取有效干预措施、科学控制BMI、合理膳食、加强体育锻炼可以预防和控制NAFLD的发生和发展。  相似文献   

2.
王丽萍  何玉然  周惠 《河北医药》2013,(24):3790-3792
非酒精性脂肪性肝病(NAFLD)是目前临床上最为常见的肝病之一,包括单纯性脂肪肝(NAFL)、脂肪性肝炎(NASH)和NASH相关性肝硬化3种病理类型。随着社会经济的发展,人民生活水平的日益提高,NAFLD的患病率逐年增加,发病呈低龄化趋势,已成为一种危害人类健康的常见的慢性肝脏疾病。我们就2010—2012年来我院就诊的298例NAFLD患者进行了回顾性分析,调查NAFLD与血压、腰围、体重指数(BMI)、血清生化指标变化的关系,预测影响NAFLD的危险因素,探讨防治措施以减少NAFLD的患病率及延缓其发生发展,结果报道如下。  相似文献   

3.
非酒精性脂肪性肝病(NAFLD)是一种与遗传和环境因素密切相关的代谢性疾病,可发展为肝纤维化、肝硬化,以致肝细胞癌。近年来, NAFLD的患病率逐年上升,目前还缺乏明确的药物治疗方法。中药在NAFLD防治中具有很大潜力但相关机制研究较少。越来越多的证据表明,肠道菌群与NAFLD的发生发展密切相关,肠道菌研究为阐明中药的作用机制开辟了新的视野。本文旨在介绍肠道菌群与NAFLD发生、发展的关系,解析肠道菌群调节在以中药为基础的NAFLD治疗中的作用及机制,以期为相关研究提供参考。  相似文献   

4.
细胞焦亡是一种与炎症相关的新型程序性细胞死亡,其发生与炎症小体密不可分,作为天然免疫系统的组成部分,是机体受到异常刺激后免疫系统清除有害因子进行组织修复而产生的防御反应。炎症反应可以提高机体清除损伤因子的能力,但过度活化则可能会对机体造成损害。随着研究逐步深入,细胞焦亡被认为与肝脏疾病的发生、发展密切相关。中医防治肝脏疾病由来已久,在临床中已经取得良好的疗效。研究显示,中药通过调控细胞焦亡相关通路蛋白与炎症因子,从而干预疾病的进展。现结合现代医学,对细胞焦亡在肝脏疾病中的作用机制进行归纳与总结,并对现阶段的中医治疗进展加以阐述。  相似文献   

5.
目的探讨血清抵抗素和肿瘤坏死因子(TNF-α)在非酒精性脂肪肝(NAFLD)及2型糖尿病(T2DM)发生发展中的作用,同时分析NAFLD和T2DM两种疾病的关系。方法选取T2DM合并NAFLD 51例(TDNA组),单纯T2DM不伴NAFLD 49例(T2DM组),单纯NAFLD48例(NAFLD组),健康体检者52例(CON组)。所有研究对象均测定血清抵抗素和TNF-α。采用SPSS 13.0统计软件进行数据分析。结果①与CON组比较,NAFLD组和T2DM组均有明显的胰岛素抵抗,而且TDNA组胰岛素抵抗更明显。②与CON组比较,血清抵抗素、TNF-α在NAFLD组和T2DM组均明显升高,而且在TDNA组升高更明显。③相关分析显示:血清抵抗素、TNF-α均与HOMA-IR呈正相关。④多元逐步回归分析显示:HOMA-IR、AST与血清抵抗素、TNF-α水平均独立相关。结论血清抵抗素、TNF-α与IR独立相关,在IR发生发展中起到了重要的作用,可作为预防和评价NAFLD、T2DM严重程度的检测指标。  相似文献   

6.
非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)作为世界上最常见的慢性肝病之一,一直是研究的热点。NAFLD与肥胖及相关代谢紊乱密切相关。高尿酸血症或高血清尿酸水平是发生在肥胖者身上常见的代谢异常。流行病学研究证实了血清尿酸水平与非酒精性脂肪肝显著相关,而黄嘌呤氧化酶(xanthine oxidase, XO)是控制尿酸合成的关键酶。本文着重对尿酸及控制其合成的限速酶XO在NAFLD形成中的作用进行综述;阐述了尿酸与代谢综合症(metabolic syndrome, MS)相关疾病之间的关系,如胰岛素抵抗、糖尿病和高血脂;最后介绍了XO抑制剂在各种疾病治疗中的应用。  相似文献   

7.
目的了解健康人群中非酒精性脂肪肝病(NAFLD)患病率及相关危险因素,为防治NAFLD提供依据。方法以城阳人民医院健康体检的745例人群为研究对象,以是否患NAFLD将其分为NAFLD组和对照组,收集相关资料进行显著性分析。结果 NAFLD总检出率23.0%,有明显的家族史、性别、年龄差异;NAFLD组各危险因素检出率均高于对照组;除HDL,NAFLD组各临床指标均值均高于对照组;Logistic回归分析显示家族史、年龄、BMI、SBP、TG、UA、FINS、CHD、HT、HDL与NAFLD的发生密切相关。结论家族史、肥胖、年龄、高血压、TG、UA、FINS、CHD、HT升高是NAFLD的危险因素,HDL是其保护因素。  相似文献   

8.
非酒精性脂肪性肝病(NAFLD)是一种常见的慢性代谢性疾病,其主要特征为肝脏脂肪堆积。NAFLD的发生和发展与多种代谢异常相关,包括肥胖、糖尿病和高血脂等。由于其在全球范围内的高发病率和危险性,NAFLD已成为公共卫生领域的一个重要问题。然而到目前为止,NAFLD的治疗方法非常有限,至今欧美和我国均无相关药物获批上市,且近年来新药临床试验并不顺利。本文综述了NAFLD治疗靶点、新药临床研究进展及治疗新途径,此外总结了NASH临床试验高失败率的原因并提出了相应解决方案,旨在为新药研发提供思路与参考。  相似文献   

9.
《中国药房》2014,(42):3998-4003
目的:综述孕甾烷受体(Pregnane X receptor,PXR)与内外源性物质代谢及相关疾病的研究进展,为后续研究提供参考。方法:查阅近年来国内外关于PXR与内外源性物质代谢及相关疾病的文献。结果:PXR参与机体的糖脂代谢及下游代谢酶的转录表达过程,不但与肥胖糖尿病的发生发展相关联,参与物质分解和机体功能稳定的维持,还与药物的疗效作用及癌症的发生发展相关。结论:PXR是机体物质能量代谢的枢纽之一,其功能状态影响着下游靶基因的状态,并因此与疾病发生关联。  相似文献   

10.
目的:探讨非酒精性脂肪性肝病(NAFLD)与小肠细菌过度生长(SIBO)的关系,进一步了解NAFLD患者SIBO的发生率及肠源性内毒素血症(IETM)对肿瘤坏死因子-α(TNF-α)、肝纤维化水平的影响,评价其在NAFLD发生发展过程中的作用。方法选择2013年2~8月本院经B超及病史诊断为NAFLD患者32例,行乳果糖氢呼气试验(LHBT)检测,根据LHBT结果将32例NAFLD患者分为SIBO阳性组和SIBO阴性组。对两组IETM、TNF-α、肝纤维化指标进行检测。结果 IETM、TNF-α在SIBO阳性组和SIBO阴性组比较差异均有统计学意义;SIBO阳性组TNF-α、肝纤维化指标有逐渐增高的趋势,两者均与IETM呈正相关。结论 SIBO和内毒素血症等机制促进NAFLD的发生和发展。  相似文献   

11.
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.  相似文献   

12.
Harrison SA  Di Bisceglie AM 《Drugs》2003,63(22):2379-2394
Nonalcoholic fatty liver disease (NAFLD) is a well recognised form of chronic liver disease that has recently gained greater recognition. Originally described in the late 1950s, NAFLD is currently considered the leading cause of abnormal liver enzyme levels in the US, closely paralleling the increase in obesity and diabetes mellitus. NAFLD has a worldwide distribution, affecting both adults and children, and typically is seen in association with obesity, diabetes, hypertension and hypertriglyceridaemia. Most patients are asymptomatic and usually present with mild elevations in aminotransferases. The natural history of NAFLD is not clearly defined but progression to cirrhosis and end-stage liver disease is well recognised in some patients. The accumulation of hepatic steatosis is thought to occur initially, primarily through hepatic and peripheral insulin resistance, which leads to altered glucose and free fatty acid metabolism. The progression from simple fatty liver to more severe forms of NAFLD (nonalcoholic steatohepatitis and cirrhosis) is much less clear but evidence suggests that oxidative stress may preferentially enhance proinflammatory cytokines, which leads to cellular adaptations and dysfunction followed by development of inflammation, necrosis and fibrosis. Therapeutic modalities remain limited and are largely focused on correcting the underlying insulin resistance or reducing oxidative stress. However, at the present time, there are several limitations to the current potential therapies, mainly because of the lack of large-scale, prospective, randomised studies, as well as clearly defined histological endpoints. Ultimately, the future for potential therapeutic modalities to treat this disease are quite promising, but further research is needed to clearly demonstrate which therapy or therapies will be effective at eliminating fatty liver disease and its potential complications.  相似文献   

13.
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.  相似文献   

14.
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.  相似文献   

15.
Introduction: The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) is high and it is associated with poor prognosis. Hepatic steatosis results as a consequence of excessive hepatic lipid accumulation which correlates with insulin resistance and lipotoxicity, with subsequent oxidative stress, inflammation, apoptosis and fibrosis.

Areas covered: This article presents the main pathophysiologic mechanisms and currently available drugs evaluated for their therapeutic effects on NAFLD/nonalcoholic steatohepatitis (NASH) and drugs under development that target relevant pathogenetic pathways. However, to date there is no particular drug approved for treatment of NAFLD in patients with T2D.

Expert commentary: Early recognition and intervention are essential to ameliorate disease progression. Specific recommendations are still needed for NAFLD/NASH screening and diagnosis and therapeutic algorithm in patients with T2D. Lifestyle optimization with significant weight loss is a key intervention in patients with NAFLD and T2D. Pioglitazone, liraglutide, vitamin E, OCA and pentoxifylline have proven some histological improvements in NASH and omega 3-PUFAs were shown to decrease liver fat, but no specific recommendation can be made for treatment of NASH. Perhaps a combination of agents that target different pathogenic pathways are needed to better control disease progression, but more robust evidence for these agents is still needed.  相似文献   

16.
Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease in the world. It describes a term for a group of hepatic diseases including steatosis, fibrosis, and cirrhosis that can finally lead to hepatocellular carcinoma. There are many factors influencing NAFLD initiation and progression, such as obesity, dyslipidemia, insulin resistance, genetic factors, and hormonal changes. However, there is also lean-NAFLD which is not associated with obesity. NAFLD is considered to be a sexually dimorphic disease. In most cases, men have a higher prevalence for the disease compared to premenopausal women.

Areas covered: In this review, we first summarize the NAFLD disease epidemiology, pathology, and diagnosis. We describe NAFLD progression with the focus on sexual and genetic differences for disease development and pharmacological treatment. Personalized treatment for multifactorial NAFLD is discussed in consideration of different factors, including genetics, gender and sex.

Expert opinion: The livers of female and male NAFLD patients have different metabolic capacities which influence the metabolism of all drugs applied to such patients. This aspect is not yet sufficiently taken into account. The liver computational models might quicken the pace toward assessing personalized disease progression and treatment options.  相似文献   


17.
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.  相似文献   

18.
Non-alcoholic fatty liver disease (NAFLD) is common in obesity. However, weight reduction alone does not prevent the progression of NAFLD to end-stage disease associated with the development of cirrhosis and liver disease. In a previous experiment, 50% ethanol extract of Acanthopanax senticosus stem bark (ASSB) was found to reduce body weight and insulin resistance in high fat diet-induced hyperglycemic and hyperlipidemic ICR mice. To evaluate the anti-steatosis action of ASSB, insulin-resistant ob/ob mice with fatty livers were treated with ASSB ethanol extract for an 8 week-period. ASSB ethanol extract reversed the hepatomegaly, as evident in reduction of % liver weight/body weight ratio. ASSB ethanol extract also specifically lowered circulating glucose and lipids, and enhanced insulin action in the liver. These changes culminated in inhibition of triglyceride synthesis in non-adipose tissues including liver and skeletal muscle. Gene expression studies confirmed reductions in glucose 6-phosphatase and lipogenic enzymes in the liver. These results demonstrate that ASSB ethanol extract is an effective treatment for insulin resistance and hepatic steatosis in ob/ob mice by decreasing hepatic lipid synthesis.  相似文献   

19.
INTRODUCTION: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are part of the same metabolic defect, both having insulin resistance as the main pathogenic mechanism and sharing similar outcomes (i.e., cardiovascular and liver-related mortality). The prevalence of NAFLD is expected to rise, owing to the increasing worldwide prevalence of obesity and MetS; therefore, the identification of factors responsible for disease progression is essential to devise therapeutic strategies. AREAS COVERED: The available and potential future treatments for NAFLD in combination with MetS are reviewed in this paper, following an extensive literature search and personal experience. EXPERT OPINION: All NAFLD patients should be evaluated for their metabolic, cardiovascular and liver-related risk. Weight loss through lifestyle intervention remains the most comprehensive and safe treatment of NAFLD and associated MetS; however, > 50% of patients fail to achieve target weight loss. Pharmacologic treatment seems to be important for these patients and for NAFLD cases with more advanced liver disease. It temporarily reverses metabolic alterations, but liver disease progresses after the treatment is stopped. Although current treatments are unsatisfactory, new drugs have been proposed and a few innovative compounds are in the pipeline of pharmaceutical companies. Before pharmacologic treatment can be routinely recommended for NAFLD, long-term randomized trials are needed, along with assessments of the safety and benefits of drugs on proper histological outcomes or validated surrogate markers. The intensive control of individual features of MetS remains mandatory.  相似文献   

20.
Background Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) are frequent causes of chronic liver disease. In recent years, there have been significant revelations as regards the relationship between NAFLD and CHC. Aim To conduct a systematic, evidence‐based review of the epidemiology, pathophysiology and potential treatments of coexistent NAFLD and CHC. Methods The terms such as hepatitis C, fatty liver, NAFLD, nonalcoholic steatohepatitis and steatosis were searched on PubMed up to January 2008. References from selected articles and pertinent abstracts were also included. Results Hepatic steatosis affects up to 80% of patients with CHC and is dependent on both viral and host factors. While insulin resistance (IR) is associated with hepatic steatosis and hepatitis C virus, genotype‐specific pathogenic mechanisms have been identified and are currently the focus of intense investigation in the literature. Clinical implications of concurrent NAFLD, CHC and IR include increased disease progression, elevated risk of hepatocellular carcinoma, and decreased response to antiviral therapy. Conclusions NAFLD and IR are common in patients with CHC virus infection. IR is a driving force in the development of hepatic steatosis. Because of the clinical implications of hepatic steatosis and IR in the setting of CHC, further studies evaluating treatments, which may increase response to antiviral therapy, are needed.  相似文献   

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