乳清蛋白对非酒精性脂肪性肝病大鼠肝脂肪变的防治作用

目的观察乳清蛋白(WP)对大鼠非酒精性脂肪性肝病(NAFLD)的防治作用。方法将35只SD大鼠随机分成对照组、模型组和治疗组,后者是在给予高脂饲料喂养的同时加用WP液灌胃干预,6周后观察各组大鼠体重、肝重、肝指数、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、甘油三酯(TG)、总胆固醇(TC)以及肝组织学改变。结果模型组大鼠肝组织病理学检查显示明显脂肪变,脂肪变积分为2.8±0.4,NAFLD活动度积分(NAS)为6.2±0.9,均明显高于对照组(0.8±0.5,P<0.01及0.9±0.7,P<0.01);动物体重、肝重、肝指数和生化指标均高于对照组,其中肝指数为3.5±0.2,ALT为42.4±7.5u/l,差别有统计学意义(P<0.01);与模型组比,治疗组动物体重和生化指标均有改善,其中ALT为34.8±5.6U/l和TG为0.2±0.1mmol/l,明显低于模型组(分别为42.4±7.5U/l,P<0.01和0.6±0.5mmol/l,P<0.05);肝细胞脂肪变积分为1.6±0.9,NAS为2.9±1.4,也明显下降(P<0.01)。结论 WP对NAFLD大鼠肝脂肪变有防治作用,可能与改善血脂代谢,减少肝脏脂质沉积以及抑制肝脏炎症反应有关。     

瘦素在大鼠非酒精性脂肪性肝病中的作用

目的探讨瘦素与非酒精性脂肪性肝病（NAFLD）肝脂肪变性程度和炎症活动度的关系。方法40只SD大鼠随机分为4组：正常对照组、非酒精性脂肪肝模型：A组（高脂喂养8周）、B组（高脂喂养12周）、C组（高脂喂养16周）。测定各组血清瘦素、白介素10（IL-10）、白介素12（IL-12）、白介素15（IL-15）;评价各组大鼠肝脂变程度和炎症活动度积分水平。结果模型组脂肪变性明显,炎症活动度记分均显著高于正常对照组（P〈0.01）,模型C组炎症活动度记分水平显著高于模型A、B组（P〈0.01）。模型组瘦素水平均显著高于正常对照组（P〈0.01）,模型B组瘦素水平显著高于模型A组（P〈0.01）。模型C组IL-10水平显著低于模型A、B组及正常对照组（P〈0.01）;模型C组IL-12水平显著高于模型A、B组及正常对照组（P〈0.01）;模型C组IL-15水平与模型A、B组有显著差异（P〈0.05）。瘦素与NAFLD肝脂肪变性程度有相关性（R2=0.378,P〈0.05）;IL-10、IL-12、IL-15与NAFLD炎症活动度相关（R2=0.551,P〈0.01）。结论本实验初步认为,瘦素可能是影响NAFLD肝脂肪变性程度的重要因素;IL-10、IL-12、IL-15对NAFLD炎症活动可能有一定影响。     

禁食疗法防治非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病(NAFLD)是一种无过量饮酒史、以弥漫性肝细胞内脂肪变性为主要特征的临床病理综合征,与代谢综合征、肥胖症密切相关[1,2]。NAFLD是全球目前最常见的慢性肝病,是导致终末期肝病和肝细胞癌的主要原因之一[3]。治疗NAFLD的首要目标为减肥和改善胰岛素抵抗,生活方式干预是NAFLD患者的主要防治方法[4-6]。禁食疗法是生活方式干预中饮食干预的一种,大量研究报道,禁食疗法能够减轻体重、延缓衰老、调节免疫、防治肿瘤等。     

腺苷酸活化蛋白激酶对糖尿病大鼠非酒精性脂肪性肝病的影响

目的 观察腺苷酸活化蛋白激酶（AMPK）在糖尿病大鼠肝脏的表达,探讨其在非酒精性脂肪性肝病（NAFLD）发病中的作用.方法 40只雄性SD大鼠随机分为正常对照（NC）组、饮食诱导肥胖（DIO）组、糖尿病（DM）组.采用Western-blot方法测定肝脏AMPK蛋白表达;HE染色后观察肝脏形态学变化.结果 DIO组血清FIns、HOMA-IR及肝脏TG含量均较NC组升高;DM组FIns、HOMA-IR较NC组及DIO组升高;DIO组肝AMPK蛋白较NC组降低（P＜0.05）;DM组肝AMPK蛋白表达较DIO组降低（P＜0.05）;DM组肝脏磷酸化腺苷酸活化蛋白激酶（p-AMPK）表达较NC组降低（P＜0.01）.结论 AMPK可能参与了肥胖及糖尿病大鼠NAFLD的发生发展.     

非酒精性脂肪性肝病治疗进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)已成为目前全球最主要的慢性肝病病因,是当前研究的热点问题,其预防和治疗也成了研究的重点和难点,目前尚无批准上市的特异性药物及明确的治疗方案,本文针对NAFLD的相关治疗及新兴靶向药物作一概述,给临床医师提供参考。     

非酒精性脂肪性肝病研究新进展

非酒精性脂肪性肝病( non- alcoholic fatty liver disease,NAFLD)是指除外酒精和其他明确的肝损害因素所致的,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,包括单纯性脂肪性肝病以及由其演变的脂肪性肝炎和肝硬化.NAFLD是21世纪全球重要的公共健康问题之一,也是常见的慢性肝病.     

非酒精性脂肪性肝病治疗进展

非酒精性脂肪性肝病无特效治疗方法,目前以生活方式调节为基础,必要时辅以药物治疗。本文从生活方式调节和药物治疗两方面回顾近年来的治疗研究进展。     

非酒精性脂肪性肝病治疗策略

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非酒精性脂肪性肝炎（NASH）和肝硬化。在欧美等发达国家,NAFLD发病率可达到20％～30％,在亚太地区成人NAFLD患病率亦达到12％～24％,而且目前仍呈上升趋势。     

降脂药防治非酒精性脂肪性肝病临床价值

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,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和肝硬化,胰岛素抵抗和遗传易感性与其发病关系密切.目前关于非酒精性脂肪性肝病的治疗主要以饮食控制及运动减重为主,对于血脂紊乱经基础治疗和(或)应用减肥降糖药物1个月以上,仍呈混合性高脂血症或高脂血症合并2个以上危险因素者,需考虑加用贝特类、他汀类或普罗布考等降血脂药物.本文就降脂药在NAFLD防治中的应用做一综述.     

儿童非酒精性脂肪性肝病流行病学现状及防治进展

非酒精性脂肪性肝病（NAFLD）是中国儿童最常见的肝脏疾病,且与肥胖、糖尿病、代谢综合征等疾病密切相关,严重影响儿童及青少年的生长发育和身体健康。近年来,儿童NAFLD得到了越来越多的关注。文章概述儿童NAFLD的流行病学、发病机制与诊疗现状,以期提高对疾病认识,做好儿童NAFLD的防治工作。     

Sampling variability of liver biopsy in nonalcoholic fatty liver disease

BACKGROUND & AIMS: In nonalcoholic fatty liver disease (NAFLD), the distinction between steatosis and steatohepatitis (NASH) and the assessment of the severity of the disease rely on liver histology alone. The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH. METHODS: Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 samples collected. The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the kappa reliability test. RESULTS: No features displayed high agreement; substantial agreement was only seen for steatosis grade; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies and lobular inflammation displayed only slight agreement. Overall, the discordance rate for the presence of hepatocyte ballooning was 18%, and ballooning would have been missed in 24% of patients had only 1 biopsy been performed. The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy. Intraobserver variability was systematically lower than sampling variability and therefore could not account for most of the sampling error. CONCLUSIONS: Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma; therefore, sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies.     

非酒精性脂肪性肝病与代谢综合征指标变化的相关性分析

目的探讨中老年人群中非酒精性脂肪性肝病(NAFLD)与代谢综合征相关指标变化的关系。方法收集2010—2011年暨南大学附属第一医院40岁以上体检人群腹部B超检查的数据,用多因素Logistic回归分析体重指数(BMI)、空腹血糖(FBG)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)、丙氨酸转氨酶(ALT)、血尿酸(UA)的变化值与NAFLD变化的关系。结果 2年内男性组和女性组NAFLD检出率都在增加,男性新增NAFLD总检出率为13.7%,明显高于女性新增NAFLD检出率7.5%(P<0.05);男性和女性的NAFLD消减率都是5.5%,且峰值都在60岁年龄组;BMI变化值与新增NAFLD密切正相关,BMI变化值的OR=1.474(95%CI 1.184～1.811),而TG和FBG的变化值与新增NAFLD无相关性;TG和BMI的变化值与NAFLD的消减呈负相关,TG变化值的OR=0.653(95%CI 0.508～0.838),BMI变化值的OR=0.628(95%CI 0.460～0.857),而FBG变化值未发现与NAFLD消减有相关性。结论 BMI变化值与NAFLD发生有密切相关性,TG和BMI的变化值与NAFLD的消减呈负相关,是影响NAFLD变化的重要因素之一。     

Apoptosis in nonalcoholic fatty liver disease: diagnostic and therapeutic implications

Pathological increases in cell death in the liver as well as in peripheral tissues has emerged as an important mechanism involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). An increase in hepatocyte cell death by apoptosis is typically present in patients with NAFLD and in experimental models of steatohepatitis, while an increase in adipocyte cell death in visceral adipose tissue may be an important mechanism triggering insulin resistance and hepatic steatosis. The two fundamental pathways of apoptosis, the extrinsic (death receptor-mediated) and intrinsic (organelle-initiated) pathways, are both involved. This article summarizes the current knowledge related to the distinct molecular and biochemical pathways of cell death involved in NAFLD pathogenesis. In particular, it will highlight the efforts for the development of both novel diagnostic and therapeutic strategies based on this knowledge.     

Interaction of Type 2 diabetes and nonalcoholic fatty liver disease

Evauation of: Kasturiratne A, Weerasinghe S, Dassanayake A et al. Influence of non-alcoholic fatty liver disease on the development of diabetes mellitus. J. Gastroenterol. Hepatol. 28(1), 142–147 (2013).

It has been a few decades that Type 2 diabetes has been clearly linked to the development and progression of nonalcoholic fatty liver disease (NAFLD). In a recent study reported by Kastuiratne et al., the reverse scenario is also reported. In this study, a cohort of Sri Lankan adults were evaluated for NAFLD by ultrasound and for the presence of Type 2 diabetes. Those without diabetes at baseline were followed prospectively for 3 years and assessed for incident diabetes. On multivariate analysis, after adjustment for a number of factors (age, impaired fasting glucose, BMI, waist circumference, elevated ALT, family history of diabetes and presence of hypertension and hyperlipidemia), NAFLD was the only predictor of incident diabetes in those with and without impaired fasting glucose at baseline. This study adds to the growing evidence connecting NAFLD to Type 2 diabetes and highlights the importance of its recognition in an effort to target those at the highest risk of diabetes for lifestyle and pharmacologic intervention.     

Current concepts in the pathogenesis of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of chronic liver disease, representing the leading cause of hepatology referral in some centres. However, its pathophysiology is not completely understood. Insulin resistance is one of the major mechanisms involved in disease prevalence and progression. Owing to the lack of an effective pharmacological therapy, recommendations on treatment are scarce and are based mainly on lifestyle changes, including diet and exercise. A review of the current literature on pathogenesis of NAFLD is presented in this article.     

非酒精性脂肪性肝病患者肝纤维化指标与血清尿酸水平关系分析

[目的]分析非酒精性脂肪性肝病（nonalcoholicfattyliverdisease,NAFLD）患者肝纤维化指标与血清尿酸水平的相关性。[方法]人选符合B超诊断的60例NAFLD患者,其中脂肪肝程度轻度者21例、中度22例、重度17例,并选取40例健康体检者为正常对照组,对所有入选者进行血液生化指标[三酰甘油（TG）、总胆固醇（Tc）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、血清肌酐（SCr）、血清尿酸（SUA）、谷草转氨酶（AST）和丙氨酸转移酶（ALT）]和肝纤维化指标[透明质酸（HA）、层黏蛋白（LN）、Ⅲ型前胶原肽（PCm）、Ⅳ型胶原（CⅣ）]检测,并将血清SUA与肝纤维化指标进行偏相关性分析。[结果]与正常对照组相比,NAFLD组中脂肪肝中度患者TG、SUA、AST水平均显著升高;重度患者TC、LDL-C、SCr、AST、ALT、TG、SUA水平均显著升高,HDL-C水平极显著降低。NAFLD组患者的Pcm和HA均显著升高;脂肪肝中、重度患者CⅣ显著升高。NAFLD组患者SUA水平均与Pcm有显著正相关性,脂肪肝中度患者SUA水平与HA呈显著正相关。[结论]NAFLD患者多项血液生化指标及肝纤维化指标异常,其中,SUA与肝纤维化指标PCIII有正相关性。     

检测视黄醇结合蛋白4在非酒精性脂肪性肝病中的意义

目的探讨非酒精性脂肪性肝病(NAFLD)患者血清视黄醇结合蛋白4(RBP4)的临床意义。方法选择NAFLD肝患者62例,正常对照60例,采用ELISA方法测定空腹血清RBP4,同时检测其血糖、血脂、肝功能及胰岛素水平,并计算胰岛素抵抗指数(HOMA-IR)。结果与正常对照组比较,NAFLD患者的空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、低密度酯蛋白(LDL-C)、血清胰岛素(FINS)、HOMA-IR、ALT、AST和RBP4显著增高(P<0.01),而且NAFLD患者治疗后血清RBP4水平显著降低。相关分析显示,血清RBP4与FBG、TC、TG、FINS、HOMA-IR呈正相关。结论在NAFLD的发病过程中,RBP4可能参与其发病,在其早期诊断和评判肝脏损害程度中有一定的临床意义。     

MicroRNAs as biomarkers and regulators of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a complicated disease affected by the interaction of environmental and genetic factors; however, the precise pathogenesis of the disease has not been fully determined. There is a need to better understand the pathogenesis of NAFLD and to identify non‐invasive diagnostic modalities. Recent advances in systematic biology and epigenetics have improved our understanding of the genotype–phenotype relationships in NAFLD. MicroRNAs (miRNAs) are important regulators of a wide range of biological processes. MiRNAs are extremely stable and protect from RNAase‐mediated degradation in body fluids, making them attractive candidate biomarkers for the early detection of the disease and the monitoring of disease progression. In this review, we summarized the current knowledge on miRNAs as potential biomarkers of NAFLD at different stages and for the prognosis of advanced diseases. Furthermore, we discussed the implications of miRNAs that functioning in lipid metabolism and hepatic steatosis as well as in hepatic inflammation and fibrosis with regard to the pathogenesis of NAFLD.     

Hepatic fat as clinical outcome and therapeutic target for nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of advanced liver disease in Western countries. NAFLD is defined in the presence of increased hepatic fat content, which is mainly stored under the form of neutral lipids within intracellular droplets and is not explained by at risk alcohol intake. In order to understand the pathogenesis, monitor the progression and find novel treatments for this condition, previous research efforts mainly addressed the role of inflammation. However, very recent data seem to suggest that hepatic lipid accumulation may be involved in NAFLD pathogenesis by driving secondary inflammation and fibrosis progression. Here, we will briefly review the novel results derived from natural history, genetics, imaging studies and therapeutic trials that support the notion that hepatic fat accumulation may represent a major clinical outcome and therapeutic target for NAFLD. Indeed, prospective and genetic data are consistent with hepatic fat being a driver of NAFLD progression. Furthermore, new technologies will render possible to monitor hepatic fat content without the need of invasive assessment, thereby allowing to identify patients at higher risk, and to monitor the response to drugs that act by decreasing hepatic lipid accumulation.