非酒精性脂肪性肝病与心血管疾病的相关性分析

目的：探讨非酒精性脂肪性肝病（NAFLD）与心血管疾病（CVD）的关系。方法根据CT检查结果将研究对象分为NAFLD患者（48例）和健康人（43例）,超声测定外周血管硬化和颈动脉内膜中层厚度（IMT）等相关指标,检测生化和内皮舒张功能指标,心脏CTA检测冠状动脉粥样病变。结果 NAFLD患者可溶性细胞间黏附分子-1[sICM-1,（185.1±36.2）ng/ml]、血内皮素-1[ET-1,（104.8±19.3）pg/ml]和臂踝脉搏波速度[baPWV,（15.5±2.3） cm/s]显著高于健康人（85.4±17.3）ng/ml、（67.5±12.1）pg/ml和（13.6±2.4）cm/s,（P＜0.05）,而肱动脉血流介导的内皮依赖性舒张功能[FMD,（8.1±2.4）%]明显低于健康人（13.2±3.5）%,（P＜0.05）;此外,NAFLD患者颈动脉IMT厚度（1.31±0.35）mm、劲动脉（31.3%）和冠状动脉粥样斑块检出率（35.4%）均明显高于对照组（0.76±0.18）mm、9.3%和11.6%,（P＜0.05）;Pearson相关分析显示NAFLD分别与IMT、劲动脉和冠状动脉粥样斑块检出率显著正相关（P＜0.01）。结论 NAFLD与CVD密切相关,NAFLD患者可能存在血管内皮功能障碍,应定期进行IMT和粥样斑块检测。     

The cardiovascular risk of patients with carotid artery stenosis

It is commonly accepted that a relationship exists between coronary and carotid arterial disease, given that the prevalence of coronary artery disease (CAD) in patients with carotid stenosis is as high as 77%, depending on the population studied. Elevated cardiovascular (CV) risks are apparent in patients with either asymptomatic or symptomatic carotid stenosis. Patients with asymptomatic carotid stenosis are at about a three-fold higher risk of CV death/myocardial infarction compared with a matched population without carotid stenosis, and this risk may be even higher among patients with symptomatic carotid stenosis. Thus, antiplatelet and lipid-lowering therapies are indicated not only to prevent stroke, but also especially to lower elevated CV risks. Carotid revascularization has become well established in patients with symptomatic carotid stenosis, which is associated with significant absolute risk reductions in terms of recurrent stroke, but remains controversial for patients with significant but asymptomatic carotid stenosis. Carotid revascularization in those with asymptomatic carotid stenosis seems to principally benefit patients with specific clinical/imaging features indicating a high risk of stroke. Screening and treatment of asymptomatic CAD can be beneficial for patients with recently symptomatic carotid stenosis and especially for those for whom surgical or endovascular carotid revascularization is planned. Because evidence of the benefits afforded by prophylactic revascularization of asymptomatic carotid artery stenosis in all CABG candidates (in terms of reducing perioperative stroke) is lacking, it may be reasonable to restrict prophylactic carotid revascularization to patients at the highest risk of postoperative stroke, thus those with severe bilateral lesions or a history of prior stroke/transient ischemic event.     

冠心病患者伴非酒精性脂肪性肝病的临床特征分析

目的 分析冠心病(CAD)伴非酒精性脂肪性肝病(NAFLD)患者的临床特征.方法 234例接受冠状动脉造影检查的患者,并有糖、脂代谢指标及腹部超声检查结果,男性148例,女性86例,平均年龄66.6岁.应用冠脉狭窄指数(CSI)评价冠状动脉病变严重程度,代谢综合征采用2007年中国成人血脂异常防治指南中关于代谢综合征的诊断标准.结果 234例研究对象中,62例患者为NAFLD.与无NAFLD组相比,NAFLD患者中心性肥胖的患病率明显升高(75.8%对50.0%,P<0.01).CAD伴NAFLD在60岁以下患者中的发生率显著高于60岁以上者(27.4%对13.7%,P=0.005).尽管CAD亚组与CAD合并NAFLD亚组的CSI评分差异无统计学意义(P>0.05),但后者的年龄明显低于CAD亚组(P=0.006).Logistic回归分析显示中心性肥胖为NAFLD的独立危险因子(β:1.701,P<0.001).Logistic回归与多元逐步回归分析发现,年龄分别是影响冠脉病变的独立危险因素(β=0.032,P=0.027)以及影响CSI评分的主要因素(β=0.125,P=0.022).结论 中年肥胖及脂肪肝人群应当重视冠心病的筛查.     

Circulating microRNAs in patients with non-alcoholic fatty liver disease

AIM: To identify novel non-invasive biomarkers for non-alcoholic fatty liver disease(NAFLD). METHODS: Twenty patients with histologically proven NAFLD and 20 controls were included. All NAFLD cases were scored using the NAFLD activity score. The rela-tive expressions of miR-197, miR-146 b, miR-10 b, miR-181d, miR-34 a, miR-122, miR-99 a and miR-29 a were analyzed using real-time polymerase chain reaction. RESULTS: Serum levels of miR-181 d, miR-99 a, miR-197 and miR-146 b were significantly lower in biopsy-proven NAFLD patients than in the healthy controls. Serum lev-els of miR-197 and miR-10 b were inversely correlated with degree of inflammation and miR-181 d and miR-99 a were inversely correlated with serum gamma glu-tamyl transferase levels in non-alcoholic steatohepatitis patients. CONCLUSION: NAFLD is associated with altered se-rum miRNA expression pattern. This study provides clues for defining the non-invasive diagnosis of NAFLD.     

颈动脉粥样斑块与冠状动脉病变的相关性研究

目的探讨颈动脉粥样硬化斑块与冠状动脉病变的临床相关性。方法选择行冠状动脉造影确诊的冠状动脉病变患者133例。根据冠状动脉造影检查结果,按照病变严重程度,分为轻度狭窄组、中度狭窄组和重度狭窄组;按照冠状动脉病变支数,分为单支病变组、双支病变组和三支病变组;按照SYNTAX积分,分为0～22分组、23～32分组和≥33分组。超声检测入选患者颈总动脉、颈内动脉、颈外动脉及其分叉处有无斑块形成并进行粥样硬化斑块积分（AS积分）,分析各组颈动脉粥样硬化斑块及积分与冠状动脉病变的相关性。结果颈动脉粥样斑块形成例数及粥样硬化斑块积分与冠状动脉病变严重程度呈正相关（r分别为0.632、0.751）;与冠状动脉病变支数呈正相关（r分别为0.597、0.655）;与SYNTAX积分呈正相关（r分别为0.643、0.597）。冠状动脉轻度狭窄组与中度及重度狭窄组比较,单支病变组与双支及三支病变组比较,冠状动脉SYNTAX积分0～22分组与23～32分组及≥33分组比较,颈动脉粥样斑块形成例数及粥样硬化斑块积分差异均具有统计学意义（P〈0.05～0.01）;冠状动脉中度与重度狭窄组比较,双支及三支病变组比较,SYNTAX积分23～32分组比较与≥33分组比较,颈动脉粥样斑块形成例数及粥样硬化斑块积分差异无统计学意义（P均〉0.05）。结论颈动脉粥样斑块检查能够反映冠状动脉病变的情况,适合临床冠心病的普查及随访。     

Association of serum triglyceride-to-HDL cholesterol ratio with carotid artery intima-media thickness,insulin resistance and nonalcoholic fatty liver disease in children and adolescents

Background and aimsThe triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C) ratio has been reported as a useful marker of atherogenic lipid abnormalities, insulin resistance, and cardiovascular disease. We evaluated in a large sample of children and adolescents the association of TG/HDL-C ratio with early signs of morphological vascular changes and cardiometabolic risk factors including nonalcoholic fatty liver disease (NAFLD).Methods and resultsThe study population, including 548 children (aged 6–16 years), of whom 157 were normal-weight, 118 overweight, and 273 obese, had anthropometric, laboratory, liver and carotid ultrasonography (carotid artery intima-media thickness-cIMT) data collected. Subjects were stratified into tertiles of TG/HDL-C. There was a progressive increase in body mass index (BMI), BMI-SD score (SDS), waist circumference, blood pressure (BP), liver enzymes, glucose, insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein (hsCRP), and cIMT values across TG/HDL-C tertiles. The odds ratios for central obesity, insulin resistance, high hsCRP, NAFLD, metabolic syndrome, and elevated cIMT increased significantly with the increasing tertile of TG/HDL-C ratio, after adjustment for age, gender, pubertal status, and BMI-SDS. In a stepwise multivariate logistic regression analysis, increased cIMT was associated with high TG/HDL-C ratio [OR, 1.81 (95% CI, 1.08–3.04); P < 0.05], elevated BP [5.13 (95% CI, 1.03–15.08); P < 0.05], insulin resistance [2.16 (95% CI, 1.30–3.39); P < 0.01], and NAFLD [2.70 (95% CI, 1.62–4.56); P < 0.01].ConclusionTG/HDL-C ratio may help identify children and adolescents at high risk for structural vascular changes and metabolic derangement.     

非酒精性脂肪性肝病患者粪便钙卫蛋白检测及其意义*

目的 探讨粪便钙卫蛋白（FC）评估非酒精性脂肪性肝病（NAFLD）患者肠道炎症状态的应用价值。方法 纳入NAFLD和健康人,采用酶联免疫吸附试验检测粪便钙卫蛋白水平,并收集两组研究对象的一般资料和血生化指标。结果 91例正常人和81例NAFLD患者体质指数（BMI）分别为（22.6±2.4） kg/m²和（28.5±4.0） kg/m²,腰围分别为（80.9±7.9） cm和（91.6±9.5） cm,血清谷草转氨酶（AST）分别为（19.3±4.8） u/L和（33.7±18.7） u/L,谷丙转氨酶（ALT）分别为（17.5±7.1） u/L和（55.0±44.5） u/L,甘油三酯（TG）分别为（0.9±0.3） mmol/L和（2.4±2.3） mmol/L,总胆固醇（TC）分别为（4.3±0.6） mmol/L和（5.1±1.3） mmol/L,差异均有统计学意义（P<0.05）;NAFLD组FC水平为43.0（18.8~87.0）μg/g,显著高于正常人的11.4（4.6~24.4）μg/g,差异有统计学意义（P<0.00）;NAFLD组和正常人FC水平大于50 μg/g者分别为48例（59.3%）和6例（6.6%）,两者构成比差异具有统计学意义（x²=55.178,P<0.001）;相关性分析显示,NAFLD患者FC水平与BMI、腰围、血清GGT、TC水平呈正相关（r=0.725,r=0.570,r=0.292,r=0.400,P值均<0.05）;多因素分析发现,低水平的HDL、高水平的TG、BMI和TC是NAFLD发病的独立危险因素（OR=0.011,OR=13.558,OR=1.821,OR=3.086,P值均<0.01）。结论 NAFLD患者粪便FC水平升高,反映肠道可能存在一定的炎症。     

NAFLD与肝细胞癌的相关性研究进展*

非酒精性脂肪性肝病（NAFLD）已成为世界范围内最常见的慢性肝脏疾病,被认为是代谢综合征在肝脏的表现,其疾病谱从轻微肝细胞脂肪变性到非酒精性脂肪性肝炎（NASH）,进一步可发展为肝硬化或肝细胞癌（HCC）。随着肥胖及胰岛素抵抗问题的日益严重,NAFLD、NASH及其相关肝硬化、肝癌患者也日益增多。近年来研究表明,NASH可不经肝硬化阶段直接发展为HCC,具体机制尚不明确。     

Nonalcoholic fatty liver disease is associated with coronary artery disease in Koreans

AIM:To investigate whether nonalcoholic fatty liver disease(NAFLD)affects coronary artery disease(CAD)and identify candidate mediators.METHODS:Patients who underwent coronary angiography were consecutively recruited.The patients were classified into four groups by coronary artery stenosis:A,insignificant;B,one-vessel disease;C,two-vessel disease;and D,three-vessel disease.Abdominal ultrasonography was performed to determine the presence of a fatty liver and categorize by grade:0,no evidence;1,mild;2,moderate;and 3,severe.We measured not only known CAD risk factors,but also serum insulin,HOMA-index,adiponectin,interleukin-6,tumor necrosis factor-αand high-sensitivity C-reactive protein levels.RESULTS:Of the 134 patients who met the inclusion criteria,82(61.2%)had ultrasonographically diagnosed NAFLD.Among the 46 patients with CAD,37(80.4%)had evidence of a fatty liver.The two groups(A vs B-D)were significantly different in terms of age,total cholesterol,triglycerides,low-density lipoprotein levels and fatty liver.Coronary artery stenosis was strongly associated with fatty liver in a grade-dependent manner(P=0.025).In binary logistic regression,NAFLD was a significant independent predictor of CAD(P=0.03,OR=1.685;95%CI:1.051-2.702).Among the candidate mediators,the serum adiponectin level showed a trend toward lowering based on CAD progression(P=0.071).CONCLUSION:NAFLD is an independent risk factor for CAD in a grade-dependent manner.Moreover,adiponectin might be related to the pathogenesis of NAFLD.     

Nonalcoholic fatty liver disease and cardiovascular disease

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are two diseases that are common in the general population. To date, many studies have been conducted and demonstrate a direct link between NAFLD and CVD, but the exact mechanisms for this complex relationship are not well established. A systematic search of the PubMed database revealed that several common mechanisms are involved in many of the local and systemic manifestations of NAFLD and lead to an increased cardiovascular risk. The possible mechanisms linking NAFLD and CVD include inflammation, oxidative stress, insulin resistance, ectopic adipose tissue distribution, dyslipidemia, endothelial dysfunction, and adiponectin, among others. The clinical implication is that patients with NAFLD are at an increased risk of CVD and should undergo periodic cardiovascular risk assessment.     

急性脑梗死患者脑白质疏松与颈内动脉狭窄及溃疡性斑块的关系

目的探讨急性脑梗死患者脑白质疏松（LA）与颈内动脉狭窄和溃疡斑块的关系。方法连续纳入首次发病的急性脑梗死患者102例。均行头部MRI及颈部血管DSA检查,确定颈内动脉病变情况。根据MRI将患者分为LA（70例）组和无LA组（32例）,再根据LA的部位将其分为皮质下LA组（46例）和脑室周围LA组（53例）。分析LA的部位、病变的程度与颈内动脉狭窄及溃疡斑块的关系,采用多因素Logistic回归分析影响不同部位LA的相关因素。结果①LA组与无LA组颈内动脉狭窄及溃疡斑块的发生率（44.3%比56.3%,21.4%比9.4%）差异均无统计学意义,P〉0.05。②皮质下LA组中,26.1%（12/46）的患者有颈内动脉溃疡斑块,高于皮质下无LA组的10.7%（6/56）,P〈0.05;皮质下LA与颈内动脉溃疡斑块呈低度正相关,r=0.201,P〈0.05。两组颈内动脉狭窄的发生率分别为56.5%和48.2%,差异无统计学意义,P〉0.05。③脑室周围LA组与脑室周围无LA组比较,颈内动脉狭窄及溃疡斑块的发生率差异均无统计学意义,P〉0.05。④多因素Logistic回归分析显示,年龄（OR=1.071,95%CI：1.014～1.131）、高血压（OR=2.953,95%CI：1.006～8.671）、颈内动脉溃疡斑块（OR=1.949,95%CI：1.286～3.142）是皮质下LA的独立预测因素;年龄（OR=1.069,95%CI：1.010～1.131）和高血压（OR=3.293,95%CI：1.984～11.020）是脑室周围LA的独立相关因素。结论急性脑梗死患者中,颈内动脉溃疡斑块的发生可能与皮质下LA相关,与脑室周围LA无明显关系。     

Racial differences in prevalence and severity of non-alcoholic fatty liver disease

The aim of this review is to assess the evidence regarding racial differences in the prevalence and severity of nonalcoholic fatty liver disease(NAFLD). We reviewed the published literature that reported prevalence, severity, and genetic associations of NAFLD in different ethnic groups. The metabolic syndrome(MetS) has been associated with NAFLD, but each component of the MetS is present in various races in different percentages and their effect on NAFLD appears to be dissimilar. An elevated triglyceride(TG) level seems to have the strongest association with NAFLD. The latter is more prevalent in Hispanic patients; Blacks have lower TG levels and a lower NAFLD prevalence, compared to Caucasians or Hispanics. The severity of liver fibrosis is lower in some, but not all biopsy-based studies of Black patients. No study has evaluated the severity of liver disease controlling for the individual components of MetS, especially TG. Important racial differences in the prevalence of selected genetic polymorphisms, particularly PNPLA-3 and MBOAT7 have been documented, together with their effects on the prevalence of liver steatosis and fibrosis. Data on overall and liver mortality have found no significant differences according to race/ethnicity, with the possible exception of one paper reporting lower cirrhosis mortality in Black patients. We conclude that NAFLD is more prevalent in Hispanics and less in Blacks. This is supported by differences in key genetic polymorphisms associated with hepatic fat storage. However, there is presently insufficient evidence to firmly conclude that race, per se, plays a role in the development of liver fibrosis and its complications. Further studies, appropriately controlled for diet, exercise, and individual MetS parameters are needed.     

非酒精性脂肪性肝病与动脉粥样硬化之间关系的研究进展

非酒精性脂肪性肝病( NAFLD)常与肥胖、糖尿病、高血脂、高血压以及代谢综合征合并存在,认为是代谢综合征的肝脏表现。NAFLD的患病率约20％～30％,在2型糖尿病人群中NAFLD患病率更高。NAFLD与心血管疾病(CVD)关系密切,NAFLD患者的主要死亡原因是CVD。NAFLD和动脉粥样硬化(AS)关系密切,其机制可能涉及氧化应激、炎症反应、脂代谢紊乱、脂肪激素水平的变化和胰岛素抵抗等方面。本文就NAFLD和AS间的关系以及可能机制进行综述。     

Recent advances in dietary supplementation,in treating non-alcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is currently known as the most common liver problem, characterized by excessive lipid accumulation in hepatocytes,which may progress to other liver diseases such as nonalcoholic steatohepatitis, hepatic tissue fibrosis, livercirrhosis, and failure or hepatocellular carcinoma. Since NAFLD is positively associated with the development of obesity, insulin resistance, and ultimately type 2 diabetes mellitus, it is often regarded as the hepatic manifestation of the metabolic syndrome. No pharmacologic treatment has yet been proven for this disease. For most patients with presumed or confirmed NAFLD, the only proven strategy is to offer lifestyle advice that can lead to sustained weight loss. Since insulin resistance, oxidative stress, inflammation, and necro-apoptosis are involved in NAFLD pathogenesis, it seems that every potential therapeutic agent should target one or some of these pathologic events. There are many well known anti-oxidants, anti-inflammatory, and insulin sensitizer dietary supplements which have shown beneficial effects on NAFLD improvement in animal and human studies. The purpose of this review is to explore the existing evidences on dietary supplements considered to have hepatoprotective properties, and to present some proposed mechanisms by which they may protect against NAFLD.     

非酒精性脂肪性肝病合并高尿酸血症的心血管疾病风险分析

目的探讨高尿酸血症对非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)心血管疾病风险的影响及其关系。方法依据NAFLD诊断标准,纳入2009年至2015年在广州中山大学附属第一医院消化内科门诊和住院患者,年龄≥18岁,排除其他肝病及酗酒者,采用Framingham危险评分系统及颈动脉超声评估心血管疾病风险。结果共入组678例NAFLD患者,其中尿酸正常者410例,高尿酸血症者268例。行颈动脉超声检查有233例。高尿酸血症(hyperuricemia,HUA)组腰臀比、BMI、收缩压、三酰甘油(TG)、空腹血糖(FBG)、胰岛素抵抗指数(HOMA-IR)、合并代谢综合征比率高于正常尿酸组,高密度脂蛋白(HDL-C)水平低于正常尿酸组(P0.05)。男性和女性按不同尿酸水平分成4组,Framingham风险评分随尿酸水平升高而升高(P=0.012),但颈动脉内中膜厚度(carotid intima media thickness,CIMT)、颈动脉增厚与颈动脉斑块检出率不同尿酸水平间无明显差异(P值分别为0.691、0.384和0.936)。进一步分析其相关性,Framingham风险及CIMT与尿酸无相关。结论 NAFLD合并高尿酸血症患者代谢紊乱更明显,10年后的心血管疾病风险随尿酸水平的升高而升高。     

高脂饮食性非酒精性脂肪性肝病大鼠肝脏PPAR-γ表达增强

目的　探讨过氧化物酶体增值物活化受体γ(PPAR-γ)及其亚型在高脂饮食所致非酒精性脂肪性肝病(NAFLD)大鼠肝脏的表达及其意义。方法　模型组SD大鼠给予高脂肪高胆固醇饮食饲养 ,分批于实验第 8、12、2 6、2 4周处死 ,同期设普通饮食饲养大鼠作对照。免疫组织化学和RT-PCR分别检测大鼠肝脏PPAR-γ的表达。结果　模型组大鼠第 8周呈现单纯性脂肪肝 ,第 12～ 2 4周从脂肪性肝炎进展为脂肪性肝炎伴肝纤维化。免疫组织化学和RT PCR显示 ,随着造模时间延长 ,肝脏PPAR-γ的表达逐渐增强。模型组肝脏PPAR-γ1mRNA表达于第 2 4周达到高峰 (与对照组相比升高 3 .5倍 ,P <0 .0 1) ,PPAR-γ2 mRNA表达于造模第 16周时达高峰 (较对照组升高 5 .8倍 ,P <0 .0 1)。相关分析显示 ,仅PPAR-γ2 mRNA与肝脂变程度之间关系密切 (r =0 .89,P <0 .0 5 )。结论　持续 2 4周的高脂饮食可以成功复制大鼠NAFLD模型 ,模型大鼠肝脏PPAR-γ表达增强 ,NAFLD大鼠肝细胞可能部分具有脂肪细胞的特征 ,即脂肪变的肝细胞发生成脂性改变     

男性非酒精性脂肪性肝病患者血糖波动研究

选取48例糖耐量正常男性为研究对象,其中非酒精性脂肪性肝病23例为病例组,无脂肪肝25例为对照组,应用动态血糖监测系统评价血糖波动情况。结果显示,病例组平均血糖波动幅度[MAGE,（2.17±1.13对1.45±0.42）mmol/L]和血糖标准差[SDBG,（0.88±0.45对0.61±0.21）mmol/L]均高于对照组(P＜0.05)。MAGE和SDBG与体重指数、腰围和糖负荷后0.5h血糖升高值(AG30)呈正相关(均P＜0.05)。以MAGE为因变量,行多元线性回归分析显示,△G30、腰围和年龄被引入方程(P＜0.05或P＜0.01)。以SDBG为因变量,行多元线性回归分析显示,AG30和腰围被引入方程（P＜0.05或P＜0.01）。     

非酒精性脂肪肝患者肾动脉阻力指数的超声观察

目的评价非酒精性脂肪肝（NAFLD）患者肾内动脉阻力指数的变化。方法采用二维及彩色多普勒超声（CDFI）在斜冠状面检测36例健康成人和36例非酒精性脂肪肝患者双侧肾脏，分别在近肾门部取双肾段动脉与近皮质部取弓形动脉频谱，比较非酒精性脂肪肝患者与健康成人肾内动脉阻力指数的差异。结果在健康成人，左右肾长度、左右肾间同区域肾内阻力指数均无显著性差别（P〉0．05），而在非酒精性脂肪肝患者，左肾长度显著大于右肾，较健康成人显著增长；与健康成人比较，非酒精性脂肪肝病人右肾段动脉及弓形动脉RI无显著性差别，而左肾动脉阻力指数有显著性降低（P〈0．01或P〈0．05）。结论非酒精性脂肪肝患者左肾内动脉阻力指数较健康成人降低。