肠道微生态与儿童非酒精性脂肪性肝病

儿童非酒精性脂肪性肝病(non-alcoholic fattyliver disease,NAFLD)是年龄在18周岁以下的儿童及青少年肝脏慢性脂肪变性,5%以上肝细胞受累,但无过量饮酒史及其他导致肝脏慢性脂肪沉积等致病因素的临床综合征[1]。其疾病谱包括非酒精性单纯性脂肪肝(non-alcoholic fatty liver,NAFL)、非酒精性脂肪性肝炎(non-alcoholic steatohepati-tis,NASH)和及其相关的肝纤维化和肝硬化[1]。     

细胞外囊泡在非酒精性脂肪肝病中的研究进展

<正>非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)包括非酒精性单纯性脂肪肝(NAFL)、非酒精性脂肪肝炎(NASH)及其相关肝纤维化和肝硬化~([1])。肝活检是NAFLD诊断及分期的金标准,但因其有创性限制了其在临床中的应用。因此,急需一种简便、灵敏、可靠的生物学指标用于NAFLD的诊断、分级及预后判断。越来越     

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非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)是一种肝组织学改变与酒精性肝病相似但无过量饮酒史的临床综合征,主要包括单纯性脂肪浸润、非酒精性脂肪肝炎(nonalcoholic steatohepatitis,NASH)和脂肪性肝硬化三种病理类型。其发病机制包括以胰岛素抵抗为主的一次打击和以氧化应激/脂质过氧化损伤为主的二次     

单纯性肥胖患儿非酒精性脂肪肝病与胰岛素抵抗

目的探讨单纯性肥胖(肥胖)儿童发生非酒精性脂肪肝病(NAFLD)的情况及与胰岛素抵抗(IR)、血脂、体质量指数(BMI)、腰臀比(WHR)的关系。方法选择肥胖儿童90例,年龄2.5～14.3岁。其中NAFLD 24例(NAFLD组),无NAFLD 66例(无NAFLD组)。另选35例年龄、性别与其相匹配的健康儿童为健康对照组。清晨空腹测量其体质量、身高、腰围和臀围,计算BMI和WHR,同时静脉采血检测其血清胰岛素(FINS)、糖(FBG)、胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和ALT、AST等,计算稳态模型胰岛素抵抗指数(HOMA-IR=FINS×FBG/22.5),并做肝胆等部位超声检查。结果 NAFLD占肥胖儿童的26.67%;NAFLD组儿童BMI、WHR最高,其次为无NAFLD组,差异均有统计学意义(Pa<0.001);3组儿童FINS和HOMA-IR值差异均有统计学意义(Pa<0.001),NAFLD组最高,其次为无NAFLD组,均明显高于健康对照组,但FBG无明显差异;NAFLD组血清TG、LDL-C和TC水平明显高于无NAFLD组和健康对照组(Pa<0.01);HOMA-IR值与BMI、WHR、血TG、LDL-C呈正相关(r=0.402、0.256、0.239、0.180,P=0.000、0.004、0.008、0.046);BMI、WHR诊断NAFLD的受试者工作特征(ROC)曲线下面积分别为0.805和0.765(Pa=0.000)。结论肥胖儿童NAFLD的发生与IR,血TG、LDL-C、TC升高及BMI、WHR增高关系密切,BMI、WHR对儿童肥胖NAFLD具有一定的诊断价值。控制体质量,减少腰围,可减轻IR,阻止NAFLD的发生、发展。     

学龄儿童肥胖相关性脂肪肝及脂代谢紊乱的病例对照研究

目的 研究学龄儿童肥胖与非乙醇性脂肪肝病（nonalcoholic fatty liver disease, NAFLD）及脂肪代谢紊乱等相关因素的关系。方法 采用典型整群抽样方法选取北京市海淀区中等水平的4所小学和4所中学，在知情同意的前提下，从中抽取659名7～18岁肥胖儿童作为肥胖组，603名正常体重儿童作为对照组，进行问卷、身体测量、腹部B超脂肪肝检查及血清总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）水平，血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）等生化指标检测。超重、肥胖采用中国学龄儿童超重、肥胖BMI筛查标准进行评价；血脂异常的判定标准：静脉血清TC≥5.20 mmol·L-1，TG≥1.70 mmol·L-1，HDL-C≤1.03 mmol·L-1，LDL C≥3.12 mmol·L-1；肝功能异常：静脉血清ALT≥40.0 U·L-1和（或）AST≥45.0 U·L-1；NAFLD诊断依据2003年中华医学会肝脏病学分会脂肪肝和酒精性肝病学组公布的非酒精性脂肪性肝病诊断标准进行。统计方法包括计量资料的描述统计、协方差分析、卡方检验、二分类多因素Logistic回归分析及趋势卡方检验等。结果 肥胖组有3例未行脂肪肝B超检测，肥胖组B超脂肪肝和NAFLD的检出率分别为28.0%（184/656）和10.2%（67/656），对照组脂肪肝和NAFLD的检出率分别为0.3%（2/603）和0.2%（1/603），差异有统计学意义（P<0.01），肥胖组TG、TC、LDL-C水平明显高于对照组，HDL-C水平明显低于对照组（P<0.01）。肥胖同时罹患NAFLD时，血脂异常进一步加重，ALT及AST异常也更明显，以ALT升高为著；随着肥胖的加重，脂肪代谢紊乱及肝功能损害程度逐渐上升。结论 肥胖儿童伴发NAFLD较为普遍，单纯性肥胖对儿童的肝功能和脂肪代谢等均造成危害，并随肥胖程度逐渐加重，对中度以上肥胖儿童建议常规进行腹部B超检查。     

肥胖儿童非酒精性脂肪肝病及代谢综合征发病情况分析

目的 研究肥胖儿童中非酒精性脂肪肝病(NAFLD)与代谢综合征(MS)的发生情况,并探索两者之间的关系.方法 对308例在本院内分泌科住院的9～14岁肥胖儿童进行腰围、体块指数、血脂、肝功能、肝脏B超、糖耐量试验及胰岛素释放试验等各项检查,根据诊断标准分别计算发生NAFLD[包括单纯性非酒精性脂肪肝(SNAFL)、非酒精性脂肪肝炎(NASH)]和MS的患病率,并将308例肥胖患儿分为无肝脏损害的肥胖儿童组(OCWLD组),SNAFL组和NASH组,比较各组胰岛素、胰岛素抵抗(IR)指标及MS的发病率和MS组成成分的发病率.结果 (1)308例中发生NAFLD的达到203例(65.9%),其中发生SNAFL者140例(45.5%),发生NASH者63例(20.5%).(2)308例中发生MS 76例(24.7%),这76例中合并有NAFLD的64例(84.2%).NAFLD组中MS 64例(31.5%),高于OCWLD组的12例(11.4%),差异有统计学意义,但SNAFL组中MS 41例(29.3%),与NASH组的23例(36.5%)比较差异无统计学意义.(3)就单个MS的组成成分来说,OCWLD组与SNALF组比较仅在高血压的发病率上差异有统计学意义,而OCWLD组与NASH组比较在高血压、高血脂、高血糖的发病率上差异均有统计学意义;SNALF组与NASH组比较在高血脂的发病率上差异有统计学意义.随OCWLD向SNAFL和NASH发展,空腹胰岛素水平逐渐上升,IR也越加明显.但NAFLD患儿与MS患儿比较各IR指标差异无统计学意义.结论 肥胖儿童中NAFLD和MS的发生率均已相当高,MS患儿合并NAFLD的比例很高,IR是NAFLD和MS共同的发病基础,且随着NAFLD患儿病情的进展,MS成分指标越来越严重,IR也越来越严重.     

中国东部超重青少年转氨酶水平升高

Elevated transaminase levels among overweight adolescents in eastern China
　　目的我们旨在调查中国东部青少年的疑似非酒精性脂肪肝疾病(nonalcoholic fatty liver disease,NAFLD)患病率和相关因素。     

儿童非酒精性脂肪肝病研究模型

儿童非酒精性脂肪肝病(nonalcoholic fatty liver disease,NAFLD)已经成为危害儿童发育健康的重要疾病之一,但其发病机制与进展特征仍未明确。构建NAFLD特异的研究模型有助于探明及揭示相关通路在NAFLD发生发展过程中的作用。现有的儿童NAFLD研究模型主要借鉴成人模型包括饮食诱导的动物...     

肥胖青少年非酒精性脂肪肝相关因素的研究

目的 探讨肥胖青少年非酒精性脂肪肝(NAFL)发病的相关因素.方法 经超声诊断,把47例BMI≥27的15～16岁肥胖青少年分为并发NAFL组(A组)和未并发NAFL组(B组),36例BMI＜23作为正常时照组,用放免法测定空腹血清瘦素(LEP)、胰岛素(FINS),同时检测血糖(FPG)、血脂,测量身高(H)、体重(W)、腰围(WC)、臀围(HC)、肱三头肌皮褶厚度(TSF)、肩胛下皮褶厚度(SSF)、腹部皮褶厚度(ASF)及血压.计算体重指教(BMI)、腰臀比(WHR)及皮褶厚度之和(SF).结果 肥胖青少年NAFL的发生率达59.57%,其中21.42%伴有肝脏增大;肥胖并发NAFL组青少年出现血脂异常、血压升高、高瘦素及高胰岛素血症;青少年NAFL的发病与血清LEP、FINS、TC、TG、LDL-C,BMI、WHR、SF、收缩压、舒张压呈正相关(P＜0.01).结论 血清高瘦素、高胰岛素、血脂异常、血压升高及BMI、WHR、SF增加是发生非酒精性脂肪肝的危险因素.     

腰围预测肥胖儿童非酒精性脂肪性肝病的价值

目的探讨腰围预测肥胖儿童发生非酒精性脂肪性肝病(NAFLD)的价值。方法2003-06—2006-09对浙江大学医学院附属儿童医院儿科197例9~14岁肥胖儿童进行腰围、体质指数(BMI)测定,作肝脏B超检查、血清肝酶测定,并与正常对照组比较。同时对肥胖儿童进行腰围、BMI与脂肪肝严重程度、血清ALT水平的相关性分析,以及腰围、BMI诊断肥胖儿童发生NAFLD曲线下面积的ROC分析。结果肥胖组腰围[(91.99±11.03)cm]显著大于正常对照组[(66.27±4.76)cm],BMI、肝酶水平也显著高于正常对照组。197例9~14岁肥胖患儿中诊断为NAFLD者147例,占74.62%;肥胖组NAFLD患儿腰围、BMI均大于非NAFLD患儿。肥胖患儿腰围、BMI与脂肪肝严重程度、血清ALT水平均呈正相关(r=0.478、0.356、0.302、0.205,均P<0.01);腰围和BMI诊断NAFLD的ROC曲线下面积分别为0.767、0.717(均P<0.01)。结论9~14岁肥胖儿童NAFLD发生与腰围密切相关,腰围、BMI对肥胖儿童发生NAFLD有一定的预测价值。     

Fatty Liver Disease in Children—What Should One Do?

The world’s population is increasingly overweight and obese. According to the World Health Organization (WHO) as of 2010, 43 million children under the age of five were overweight. Once considered to be limited to developed countries, overweight and obese children are now found in low- and middle-income countries, though most commonly in urban areas. Furthermore the WHO now cites the conditions of overweight and obesity as being associated with more deaths around the globe than those associated with being underweight. With this increased prevalence of overweight and obese children has come a host of other medical problems including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). This review will focus on NAFLD and NASH, their definitions, epidemiology, diagnosis and treatment. The authors will also discuss NAFLD in the Indian subcontinent, and the future of NAFLD and NASH.     

Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications for future research

Although population prevalence is very difficult to establish, nonalcoholic fatty liver disease (NAFLD) is probably the most common cause of liver disease in the preadolescent and adolescent age groups. There seems to be an increase in the prevalence of NAFLD, likely related to the dramatic rise in the incidence of obesity during the past 3 decades. Despite an increase in public awareness, overweight/obesity and related conditions, such as NAFLD, remain underdiagnosed by health care providers. Accurate diagnosis and staging of nonalcoholic steatohepatitis (NASH) requires liver biopsy. The development of noninvasive surrogate markers and the advancements in imaging technology will aid in the screening of large populations at risk for NAFLD. Two distinct histological patterns of NASH have been identified in the pediatric population, and discrete clinical and demographic features are observed in children with these 2 patterns. The propensity for NASH to develop in obese, insulin-resistant pubertal boys of Hispanic ethnicity or a non-Hispanic white race may provide clues to the pathogenesis of NAFLD in children. The natural history of pediatric NASH has yet to be defined, but most biopsies in this age group demonstrate some degree of fibrosis. In addition, cirrhosis can be observed in children as young as 10 years. While the optimal treatment of pediatric NAFLD has yet to be determined, lifestyle modification through diet and exercise should be attempted in children diagnosed with NAFLD. A large, multicenter trial of vitamin E and metformin is underway as part of the NASH clinical research network.     

基因拷贝数变异与汉、维、哈三民族儿童超重/肥胖患病风险之间的关联研究

目的 了解新疆汉族、维吾尔族（简称维族）、哈萨克族（简称哈族）儿童超重/肥胖患病情况与基因拷贝数变异（CNV）之间的关系。方法 以新疆伊犁、阿勒泰和克拉玛依3个城市中的幼儿园作为研究现场,采用分层整群抽样方法抽取3~7岁儿童,测量身高、体重并采集口腔黏膜脱落细胞,采用CNVplex®方法检测FTO_1、IRX3_1、IRX3_2、MC4R_1、MC4R_2等5个位点CNV。结果 调查儿童603名,其中男307名,女296名;汉族261名,维族194名,哈族148名。汉族、维族、哈族儿童超重/肥胖率分别为28.3%、10.3%、31.1%（P < 0.001）。在哈族儿童中,IRX3_1、MC4R_2两位点CNV与超重/肥胖相关（P < 0.05）。多因素logistic回归分析显示,汉族和哈族儿童发生超重/肥胖的风险分别是维族儿童的3.443倍（95%CI：2.016~5.880）和3.924倍（95%CI：2.199~7.001）;IRX3_1位点CNV是超重/肥胖的危险因素（P=0.028,OR=2.251,95%CI：1.418~5.651）。结论 IRX3_1 CNV与汉族、维族、哈族儿童超重/肥胖的患病风险有关,尤其应关注哈族儿童中IRX3_1 CNV与超重/肥胖之间的关联性。     

Liver steatosis in Polish children assessed by medicolegal autopsies

Background

Cases of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are increasing in the pediatric population. Their growing prevalence coincides with the obesity epidemic. Assessment of the incidence requires liver biopsies on a representative population sample, which are hampered by the absence of indications for invasive examination on children without clinical symptoms. The aim of the current study was to assess the incidence of liver steatosis in the population of children up to 18 years old from Lower Silesia.

Methods

We retrospectively reviewed 342 medico-legal autopsy reports from 2000 to 2009. We separated a group of 256 children whose death was caused by trauma. Liver steatosis was diagnosed according to the results of histopathological examinations and typical macroscopic imaging.

Results

In the 265 children who died from trauma, liver steatosis was reported in 11 (4.2%) children (6 boys) aged between 6 months and 18 years old. Six of the 11 children (54.5%) were found to be overweight. In all 342 children, steatosis was found in 18 (5.3%) children (13 boys), while NASH was diagnosed in 1 (0.3%). Excess body weight was observed in 55.6% (10/18) of children with steatosis.

Conclusions

Liver steatosis can occur at any age, even in infancy. Being overweight is a very important risk factor. Gross examination of the liver is insufficient for the diagnosis of steatosis because of its lower sensitivity and specificity. Verification of liver steatosis requires reference histopathological examination.     

Prolonged hepatitis caused by cytomegalovirus and non-alcoholic steatohepatitis in 16-year-old obese boy

Recently, the prevalence of non-alcoholic steatohepatitis (NASH) has been increasingly reported in patients with type 2 diabetes and obesity. NASH exists not only in adults but also in children. We report on an 16-year-old boy with prolonged hepatitis associated with NASH after cytomegalovirus hepatitis. Increased transaminase levels recovered in parallel to his weight reduction. Conclusion:Clinicians should be aware of the possibility that prolonged acute hepatitis might be associated with non-alcoholic steatohepatitis in adolescents.     

肥胖儿童脂肪肝与胰岛素抵抗的关系

目的了解肥胖儿童非酒精性脂肪肝(NASH)的发病情况及与胰岛素抵抗的关系。方法对125例肥胖儿童行肝脏B超检查及血生化检查;对其中36例肥胖伴NASH儿童和41例无并发症的单纯肥胖儿童,以及22例对照儿童空腹行口服葡萄糖耐量和胰岛素释放试验,计算体重指数(BMI)、稳态模型胰岛素抵抗指数(HOMA蛳IR)、总体胰岛素敏感指数(WBISI)和葡萄糖、胰岛素曲线下面积之比(AUCINS/AUCBG)。结果NASH在肥胖儿童中的发生率为28.8%;NASH组BMI、HOMA蛳IR、AUCINS/AUCBG均明显高于单纯肥胖组和对照组熏WBISI明显低于单纯肥胖组和对照组;单纯肥胖组HOMA蛳IR、AUCINS/AUCBG均明显高于对照组。结论肥胖儿童中NASH发生率较高;NASH儿童存在严重的胰岛素抵抗,胰岛素抵抗可能是NASH重要发病机制之一。     

外周血IL-6对新生儿脓毒症诊断价值的Meta分析

目的 系统评价外周血IL-6对新生儿脓毒症的诊断价值。方法 通过计算机检索中国知网、维普、万方、PubMed、Embase、Web of Science、Cochrane 图书馆公开发表的有关文献,检索时间截止至2014年9月。采用QUADAS量表对纳入文献进行质量评估;采用Metadisc1.4及Stata11.0软件进行异质性检验并根据异质性结果选择相应的效应模型进行定量合成;计算敏感度、特异度及其95%CI,绘制汇总受试者工作特征曲线(SROC),并计算曲线下面积(AUC)及Q*指数。结果 共计33篇文献纳入Meta分析,分析结果显示:外周血IL-6对新生儿脓毒症诊断的敏感度和特异度分别为0.79(95%CI:0.76~0.81)和0.83(95%CI:0.81~0.85),SROC的AUC为0.89,Q*指数为0.83;IL-6不增高时新生儿脓毒症发生概率为5%,IL-6增高时新生儿脓毒症发生概率提高为60%。结论 外周血IL-6对新生儿脓毒症诊断的敏感度和特异度较高,有助于早期诊断新生儿脓毒症。     

长沙市开福区小学生肥胖现状及影响因素分析

目的：了解长沙市开福区小学生超重、肥胖情况及单纯性肥胖的影响因素,为小学生肥胖的防治工作提供科学依据。方法：随机抽取长沙市开福区7~12周岁小学生4 140名,按照体重指数(BMI)法判定出单纯性肥胖,将肥胖和正常儿童设为肥胖组和对照组,对影响小学生肥胖的有关因素进行分析。结果：①长沙市开福区小学生超重及肥胖检出率分别为9.76%和7.39%,男女生肥胖率分别为9.37%和5.13%。②与正常小学生相比,肥胖小学生的BMI,腰围(WC),腰臀比(WHR),体脂百分比(%BF),收缩压(SBP),血清甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)明显升高,高密度脂蛋白胆固醇(HDL-C)明显降低。③肥胖小学生的WC,WHR与TG,LDL-C的偏相关系数大于BMI,%BF与其的偏相关系数。④儿童肥胖的危险因素可归结为常暴饮暴食、看电视时间长、进餐速度快、常吃油腻食物,而喜欢运动、运动时间长具有保护作用。结论：长沙市开福区小学生肥胖的发生率在国内处于高水平,控制儿童肥胖有助于慢性疾病的早期预防,预防儿童肥胖关键在于普及营养保健知识、注意平衡膳食和增加体力活动。