肠道益生菌辅助治疗非酒精性脂肪性肝病的系统评价

目的系统评价肠道益生菌辅助治疗非酒精性脂肪性肝病的疗效和安全性。方法电子检索Cochrane图书馆临床对照试验(2018年1期)、EMbase、PubMed、中国知网(CNKI)、维普万方数据库,检索时限均为建库至2018年1月。并人工检索相关会议论文集及查阅检索到的所有文献的参考文献,完整收集国内外关于肠道益生菌辅助治疗非酒精性脂肪性肝病的随机对照试验(RCT)研究。由2位研究者按纳入与排除标准独立筛选文献、提取资料并进行质量评价后,采用RevMan 5.3软件进行Meta分析。结果纳入14个RCT包括1 110例患者。Meta分析结果显示:(1)益生菌组肝脏生化学指标丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰转肽酶(GGT)优于安慰剂或空白对照组(P0.05);(2)益生菌组血脂指标三酰甘油(TG)、总胆固醇(TC)、低密度胆固醇(LDL)优于安慰剂或空白对照组(P0.05);益生菌组高密度脂蛋白(HDL)不优于安慰剂或空白对照组(P=0.74);(3)益生菌组空腹血糖(FBG)、体质量指数(BMI)不优于安慰剂或空白对照组(P=0.12、0.35);益生菌组胰岛素抵抗指数(HOMA-IR)、肿瘤坏死因子-α(TNF-α)优于安慰剂或空白对照组(P0.05)。结论肠道益生菌辅助治疗非酒精性脂肪性肝病可改善肝脏酶谱,也可改善血脂和胰岛素抵抗,是安全有效的辅助治疗方案,但仍需进一步循证医学证据来指导临床实践。     

非酒精性脂肪性肝病的发病机制

随着我国经济的快速发展和人们生活水平的提高,非酒精性脂肪肝病(non-alcoholic fatty live disease,NAFLD)已成为我国重要的公共卫生问题之一。目前,在我国NAFLD已成为仅次于慢性病毒性肝炎的第二大肝病,患病率达15%左右,且呈持续升高态势[1]。上海交通大学附属瑞金医院于2010年在上海地区开展的流行病学调查数据显示,40岁以上成年人的脂肪肝患病率已高达30%[2]。此外,多     

非酒精性脂肪性肝病的治疗

1引言 NAFLD是一种与胰岛素抵抗（Insulin resistance,IR）和遗传易感性密切相关的代谢应激性肝脏损伤,疾病谱包括非酒精性单纯性脂肪肝、NASH及其相关肝硬化和肝癌。NAFLD是西方常见的肝脏疾病,人口学调查表明约20％～30％的西方人患有NAFLD。随着人们生活水平的提高、生活方式的改变及医疗技术的提高,我国的NAFLD发病也呈升高趋势。     

非酒精性脂肪肝——非酒精性脂肪性肝病的诊断

脂肪肝是临床常见的疾病之一,但很多人对此认识有误区,认为无所谓,实际上肝脏是一个强大的脂肪贮存库,其与高血脂、高血压、糖尿病等多种心脑血管疾病密切相关,因此正确认识脂肪肝非常重要。该专题对非酒精性脂肪肝的诊断和治疗及其与2型糖尿病的关系作一介绍,供临床医生参考。     

不同运动形式对非酒精性脂肪肝病人肌肉与脂肪的影响

目的:研究不同运动形式对非酒精性脂肪肝(NAFLD)病人肌肉与脂肪的影响。方法:选择佛山市第一人民医院2021年1月—2021年12月诊治的84例NAFLD病人,随机将其分成抗阻组及有氧组,每组42例。有氧组开展有氧运动干预,抗阻组则开展抗阻运动干预。检测两组干预前后肝功能指标、体质指数(BMI)、腰臀比、人体成分指标、血清肿瘤坏死因子-α(TNF-α)以及固醇调节元件结合蛋白-1c(SREBP-1c)水平变化等,并分析差异是否有统计学意义。结果:干预后两组各项肝功能指标均较干预前下降(P<0.05),干预后两组间各项肝功能指标比较差异无统计学意义(P>0.05)。干预后抗阻组BMI为(25.05±4.78)kg/m²,高于有氧组的(22.87±4.21)kg/m²,且腰臀比为0.83±0.18,高于有氧组的0.71±0.14(P<0.05)。干预后抗阻组肌肉含量为(45.72±7.35)kg,高于有氧组的肌肉含量(41.57±6.04)kg,而总脂肪含量为(3.21±0.46)m²,低于有氧组的总脂肪...     

胰岛素抵抗与非酒精性脂肪性肝病的研究

目的研究胰岛素抵抗与非酒精性脂肪性肝病的关系。方法对89例非酒精性脂肪肝患者（病例组）与60例无脂肪肝肥胖者（对照组）测定血清胰岛素等指标,比较两组差异。结果非酒精性单纯性脂肪肝患者的体质指数（BMI）、腰臀比（WHR）、三酰甘油（TG）、丙氨酸氨基转移酶（ALT）、空腹血糖（FBG）、空腹胰岛素（FINS）、胰岛素抵抗指数（IR）均高于对照组,差异有统计学意义（P〈0.05）。结论胰岛素抵抗指数是非酒精性脂肪肝的危险因素。     

非酒精性脂肪肝病运动疗法的研究进展

非酒精性脂肪性肝病(Nonalcoholic Fatty Liver Disease,NAFLD)是一种与胰岛素抵抗(insulin resistance,IR)和遗传易感密切相关的代谢应激性肝脏损伤,其病理学改变与酒精性肝病(ALD)相似,但患者无过量饮酒史,疾病谱包括非酒精性单纯性脂肪肝(nonalcoholic simple fatty liver,NAFL)、非酒精性脂肪性肝炎(NASH)及其相关肝硬化和肝细胞癌[1-2]。欧美等国家成人患病率约为20%~33%,且随着年龄增长而上升[3]。近20年亚洲国家NAFLD增长迅速且呈低龄化发病趋势,中国上海、广州和香港等地区成人NAFLD患病率约为15%[2,4-5]。运动疗法能有效降     

非酒精性脂肪肝患者治疗性生活方式改变的策略和效果评价

目的探讨非酒精性脂肪肝患者治疗性生活方式改变（therapeutic life style change,TLSC）的策略和效果,旨在使患者建立良好的饮食与运动行为习惯,全面降低对其预后的不利影响。方法用食品交换法控制饮食,用能量代谢当量值监控运动量,辅以健康教育,并指导患者记生活日记等,干预3个月后进行效果评价。结果92例患者,干预前饮食控制和运动不合格者,分别占92．4％与89．1％,高热量与高脂肪的摄入者,分别占100．0％与94．1％;干预后高热量与高脂肪摄入减少,运动量增加,体重减轻,血糖、血脂值降低,健康意识增强。结论治疗性生活方式改变有利于脂肪肝患者建立健康的生活方式,全面降低对患者预后不利的影响。     

健脾利湿中药汤剂治疗非酒精性脂肪性肝病40例

目的观察健脾利湿为主方的中药汤剂治疗非酒精性脂肪性肝病的临床疗效。方法符合纳入标准的NAFLD患者79例,随机分为两组。治疗组给予健脾利湿为主方中药汤剂200ml,每日2次口服;对照组给予水林佳胶囊1．05g,每日3次口服。疗程均为12周。结果治疗组可明显改善患者临床症状及肝功、血脂,也可显著改善肝脏影像学变化（P〈0．01）。结论健脾利湿中药汤剂治疗非酒精性脂肪性肝病疗效显著,明显优于对照组。     

胰岛素抵抗与非酒精性脂肪性肝病和动脉粥样硬化

代谢综合征（MS）具有多种动脉粥样硬化（AS）和非酒精性脂肪性肝病（NAFLD）的危险因素,而胰岛素抵抗（IR）是MS重要的病理生理基础。NAFLD和AS为一多因素性疾病,IR、炎症、血脂异常和许多脂肪细胞因子作为危险因子促进AS和NAFLD的发生发展,它们相互作用参与多个病理生理过程。     

The association of non-alcoholic fatty liver disease and atrial fibrillation: a review

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes an enormous burden to human health and health-care systems all over the world. A great proportion of this burden results from increased risk of cardiovascular diseases. Atrial fibrillation (AF) is the most common chronic heart arrhythmia globally and it increases the risk of embolic stroke and heart failure. Recent studies have explored the association between NAFLD and AF with somewhat conflicting results. However, ultrasound-verified prospective studies concur that NAFLD is associated with the incidence of AF. According to epidemiological evidence, the greater the prevalence of NALFD in a population, the stronger the association with AF incidence and prevalence. Specifically, diabetic individuals with NAFLD are at the greatest risk of AF. Additionally, the risk of AF may concentrate most in individuals with advanced NAFLD, particularly those with liver fibrosis. The possible mechanistic factors between NAFLD and AF, particularly obesity and systemic inflammation, are diverse and form a complex interplaying network. However, further studies are needed to elucidate whether NAFLD has a causative role in the development of AF. The purpose of this article is to review and discuss the epidemiologic evidence and possible mechanistic links between these two conditions.

• KEY MESSAGES

• Although epidemiologic studies have provided conflicting results on the association of NAFLD and AF, prospective studies with ultrasound-verified NAFLD concur that NAFLD is associated with about 2-fold greater incidence of AF among general population and about 6-fold greater incidence among subjects with type 2 diabetes.

• The risk of AF among individuals with NAFLD is increased by other cardiovascular risk factors, especially type 2 diabetes and advanced age.

• The possible mechanistic links between NALFD and AF are diverse, with obesity and systemic inflammation having a significant role, but further studies are needed until NAFLD can be established as a causal factor in the incidence of AF.

     

非酒精性脂肪肝患者血清游离脂肪酸与胰岛素抵抗的关系

目的研究非酒精性脂肪肝(NAFLD)患者血清游离脂肪酸(FFA)水平及其与胰岛素抵抗(IR)的关系。方法测定118例NAFLD患者(NAFLD组)及103名健康体检者(正常对照组)的血清FFA并计算胰岛素抵抗指数(HOMA-IR)。结果 NAFLD组血清FFA浓度为(752.50±101.42)μmol/L,HOMA-IR为1.48±0.42,均高于正常对照组[(441.75±95.64)μmol/L,0.67±0.33](P<0.01)。NAFLD组FFA与HOMA-IR呈正相关(r=0.325,P<0.05)。结论 FFA与NAFLD密切相关,FFA致NAFLD可能通过IR起作用。     

小檗碱对非酒精性脂肪性肝病患者血清骨钙素的影响

目的:探讨小檗碱对伴糖代谢紊乱的非酒精性脂肪性肝病(NAFLD)患者的血清未羧化骨钙素(ucOC)水平的影响。方法:对伴有糖耐量受损或2型糖尿病的114例NAFLD患者,进行生活方式干预,其中57例(小檗碱组)加小檗碱治疗(0.5 g/次,每日3次),共干预16周,其余57例仅进行生活方式干预,作为对照组。评价干预前后患者ucOC水平变化及血糖、血脂和肝脏脂肪含量(HFC)等指标,分析ucOC变化的影响因素。结果:与对照组相比,小檗碱组患者血清ucOC水平升高更明显(P0.001)。校正年龄、性别和体质指数(BMI)后,小檗碱组血清ucOC的改善情况[4.60(3.50, 5.70)]仍明显优于对照组[0.96(-0.14, 2.05),P0.001],平均差异为3.64 (95%CI 1.74～5.55)。亚组分析显示,在非肥胖老年男性患者中,小檗碱升高ucOC的作用更加明显。偏相关分析显示,在校正年龄、性别后,治疗前后血清ucOC水平差值与BMI、体质量、腰围、HFC、糖化血红蛋白(HbA1c)、总胆固醇(TC)的差值负相关(P0.05)。结论:小檗碱能改善伴糖代谢紊乱的非酒精性脂肪性肝病患者代谢异常,可能与其升高血清ucOC水平有关。     

非酒精性脂肪肝对急性心肌梗死患者预后的影响

目的探讨急性心肌梗死(acute myocardial infarction, AMI)并发非酒精性脂肪肝(non-alcoholic fatty liver disease, NAFLD)患者血脂、血清炎性因子水平变化,及NAFLD对AMI预后的影响。方法 AMI患者712例,其中350例有NAFLD者为观察组,362例无NAFLD者为对照组。比较2组入院时年龄,性别比例,体质量指数(body mass index, BMI),合并高血压、2型糖尿病情况,ST段抬高型心肌梗死(ST-segment elevation myocardial infarction, STEMI)及非STEMI比率,冠状动脉病变支数,行经皮冠状动脉介入术(percutaneous coronary intervention, PCI)比率,药物治疗情况以及血清肌钙蛋白I(cardiac troponin I, cTnI)、尿酸(uric acid, UA)、同型半胱氨酸(homocysteine, Hcy)、C反应蛋白(C-reactive protein, CRP)、总胆固醇(total cholesterol, TC)、三酰甘油(triacylglycerol, TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol, HDL-C)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol, LDL-C)、白细胞计数(white blood cell count, WBC),D-二聚体(D-dimer, D-D)、血小板/淋巴细胞比值(platelet lymphocyte ratio, PLR);随访观察主要心脑血管不良事件(major cardiovascular and cerebrovascular adverse events, MACCE)发生率及生存时间;Pearson相关分析SYNTAX积分与UA等指标的相关性。结果观察组BMI[(29.00±1.41)kg/m^2]、合并2型糖尿病比率(60.57%)、SYNTAX积分[(24.50±2.37)分]及血清TC[(5.67±0.63)mmol/L]、TG[(2.31±0.27)mmol/L]、LDL-C[(3.13±0.51)mmol/L]、UA[(502.20±31.51)μmol/L]、Hcy[(16.91±1.85)μmol/L]、CRP[(22.30±0.37)mg/L]、WBC[(13.08±2.09)×10^9/L]、D-D[(1.36±0.32)g/L]、PLR(191.34±8.15)均高于对照组[BMI:(27.00±1.69)kg/m^2,合并糖尿病比率:41.99%,SYNTAX积分:(19.60±3.95)分,TC:(5.02±0.35)mmol/L,TG:(1.91±0.40)mmol/L,LDL-C:(2.38±0.55)mmol/L,UA:(446.20±51.08)μmol/L,Hcy:(13.63±1.50)μmol/L,CRP:(13.20±0.33)mg/L,WBC:(11.16±0.98)×10^9/L,D-D:(0.95±0.26)g/L,PLR:158.85±8.35](P<0.05);2组年龄,性别比例,合并高血压比率,冠状动脉病变支数,STEMI、非STEMI、PCI比率,阿司匹林等药物应用比率,血清HDL-C、cTnI水平比较差异无统计学意义(P>0.05);观察组MACCE发生率(9.71%)高于对照组(5.52%)(P<0.05),中位生存时间(14.5个月)较对照组(15.4个月)短(P<0.05);Pearson相关分析显示,SYNTAX积分与UA(r=0.876,P<0.001)、Hcy(r=0.736,P<0.001)、CRP(r=0.278,P=0.038)、TC(r=0.644,P<0.001)、TG(r=0.641,P<0.001)、LDL-C(r=0.633,P<0.001),BMI(r=0.599,P<0.001)、PLR(r=0.456,P<0.001)均呈正相关。结论 NFALD可能加剧AMI患者炎性反应,增高血脂,加重冠状动脉血管狭窄程度,增加MACCE发生率,影响AMI患者预后。     

进展性非酒精性脂肪性肝病无创性诊断的临床研究进展

非酒精性脂肪性肝病(NAFLD)目前已是世界第一大慢性肝脏疾病,为全球终末期肝病、肝细胞癌和肝移植的主要原因。NAFLD的病理变化是从单纯性肝脂肪病变进展为非酒精性脂肪性肝炎(NASH),最终可进展至中晚期肝纤维化,因此准确诊断和鉴别NASH和纤维化对NAFLD的治疗和管理是十分必要的。近年来,肝活组织检查的局限性促使无创诊断技术迅速发展。本文就进展性NAFLD(NASH及纤维化)的无创性诊断方法展开论述,明确各种新的无创性诊断手段的特点,旨在进一步优化NAFLD的临床管理,推动本领域科学研究进展。     

人体测量指标对2型糖尿病患者非酒精性脂肪肝进展的预测作用

目的:探讨人体测量学指标,包括体质指数、腰围、腰围/身高、腰臀比等,对住院2型糖尿病患者非酒精性脂肪性肝病(NAFLD)进展情况的预测作用。方法:连续纳入资料完整的住院2型糖尿病者535例,采集人口学资料、人体测量学指标和实验室化验数据。根据NAFLD进展情况,将其分为进展组和非进展组,分析两组临床特征。采用二分类logistic回归模型分析各指标与NAFLD进展的相关性;使用受试者工作曲线进行检验效力分析。结果:535例患者中,进展组患146例、非进展组389例。与非进展组相比,进展组年龄较小,体质指数、腰围、腰围/身高、腰臀比较大,三酰甘油、尿酸、丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平较高(P0.05)。二分类logistic回归模型显示,体质指数、腰围、腰围/身高、腰臀比为2型糖尿病患者发生NAFLD的独立危险因素(P=0.000)。ROC曲线分析结果显示,体质指数、腰围、腰围/身高、腰臀比预测NAFLD进展的曲线下面积(AUC)分别为0.675、0.677、0.664、0.642,截断值分别为24.23kg/m2、93.5cm、0.57、0.89(P=0.000)。结论:体质指数、腰围、腰围/身高和腰臀比均可预测2型糖尿病患者NAFLD的发生。     

Effects of lifestyle intervention on soluble CD163, a macrophage activation marker,in patients with non-alcoholic fatty liver disease

Objective: Liver macrophages play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163), a macrophage-specific biomarker, reflects disease activity in the range of liver diseases. The impact of lifestyle intervention on sCD163 in adult NAFLD patients has not been investigated.

Material and methods: We assessed 126 NAFLD patients participating in a lifestyle intervention study for sCD163 concentrations at baseline, after the three-month intervention period, and at long-term follow-up after 12 and 24?months.

Results: The median sCD163 concentration at baseline was 2.59?mg/L (IQR?=?1.78–3.63?mg/L). There was a significant decrease in sCD163 from baseline to three months follow-up (?0.64?mg/L, p?<?.001) with no difference between the four study groups (p?=?.6). At 12 and 24?months follow-up, the sCD163 concentrations had returned to baseline level (p?=?.3 and p?=?.1). Baseline sCD163 correlated with liver biomarkers and metabolic variables. There was a significantly greater decrease in sCD163 in patients who had a decrease in alanine aminotransferase (ALT) compared with patients with unchanged or increased ALT (?0.76?mg/L vs. ?0.41?mg/L, p?=?.02), and in patients with a decrease in HOMA-IR compared with individuals with no decrease (?0.86?mg/L vs. ?0.55?mg/L, p?=?.03).

Conclusion: sCD163 is associated with markers of liver necro-inflammation and glucose homoeostasis in NAFLD. Participation in a lifestyle intervention programme resulted in a significant reduction in sCD163. Our data support the utility of sCD163 as a biomarker for monitoring the efficacy of therapeutic interventions in NAFLD.     

非酒精性脂肪性肝病与胰岛素抵抗及糖脂代谢关系的研究

目的:分析非酒精性脂肪性肝病(NAFLD)患者的肝脏脂肪含量与胰岛素抵抗(IR)、糖脂代谢间的关系。方法:收集19例NAFLD患者的临床资料,同时选择17例非NAFLD患者作为对照组,询问病史及体检,检测肝功能、血脂,行口服葡萄糖耐量试验(OGTT)并测各点血糖和胰岛素水平,采用磁共振及质子磁共振波谱(1HMRS)分析对肝脏的脂肪含量进行定量测检。结果:NAFLD组患者的肝丙氨酸氨基转移酶(ALT)、血三酰甘油(TG)、OGTT各点血糖、葡萄糖曲线下面积(AUCg)、OGTT0min胰岛素、OGTT120min胰岛素、早期胰岛素分泌(ΔI30/ΔG30)、稳态模型法评估胰岛素抵抗指数(HOMA-IR)均高于非NAFLD组(P<0.05),而其高密度脂蛋白-胆固醇(HDL-C)低于非NAFLD组(P<0.05)。NAFLD组中,11例糖代谢正常者与8例糖代谢异常者相比,两者间ALT差异无统计学意义,而糖代谢正常者的γ-谷氨酰转肽酶(GGT)较低,差异有统计学意义(P<0.05)。NAFLD糖代谢正常组GGT、TG、OGTT各点血糖及AUCg均低于糖代谢异常组(P<0.05),而其OGTT0min胰岛素、OGTT120min胰岛素有高于糖代谢异常组的趋势,但差异尚无统计学意义。结论:NAFLD患者存在明显的胰岛素抵抗(IR),其肝脏脂肪含量增加与IR明显相关,ALT为最早出现异常的指标。当NAFLD患者出现糖代谢异常后,则表现为胰岛β细胞分泌功能受损,胰岛素分泌量降低,GGT异常。因此,早期控制NAFLD,对保护患者的胰岛功能、改善其糖代谢异常有重要作用。     

The effect of melatonin on treatment of patients with non-alcoholic fatty liver disease: a randomized double blind clinical trial

ObjectivesMany factors implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) are including oxidative stress, insulin resistance and abnormal production of adipokines. The aim of this clinical trial was to evaluate the effect of melatonin supplement on some important biochemical markers and signs related to NAFLD.DesignA randomized double-blind, placebo-controlled, clinical trial.SettingTwenty-four participants in the melatonin group and 21 participants in the placebo group completed the study.InterventionParticipants received 6 mg melatonin or placebo daily, 1 h before bedtime. The intervention period was 12 weeks.Main outcome measuresAnthropometric measurements, systolic and diastolic blood pressure, liver enzymes, high sensitive C‑reactive protein (hs-CRP), fatty liver grade, also leptin and adiponectin serum levels, were measured at the baseline and the end of intervention.ResultsA significant improvement was observed in weight (p = 0.043), waist circumference (p = 0.027), abdominal circumference (p = 0.043), systolic (p = 0.039), and diastolic (p = 0.015) blood pressure, leptin serum levels (p = 0.032), hs-CRP (p = 0.024), alanine aminotransferase (p = 0.011), aspartate aminotransferase (p = 0.034), also the grade of fatty liver (p = 0.020) in melatonin treated group compared with the placebo.ConclusionsAdministration of 6 mg/day melatonin had improvement effect on many factors related to NAFLD such as liver enzymes, hs-CRP, anthropometric measurements, blood pressure, leptin serum levels and the grade of fatty liver.