重视代谢相关脂肪性肝病的特征与预后临床研究

非酒精性脂肪性肝病(NAFLD)是与胰岛素抵抗和遗传易感密切相关的以肝细胞大泡性脂肪变为病理特征的慢性代谢应激性肝脏疾病,疾病谱主要包括非酒精性单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)及其相关的肝硬化和肝细胞癌(HCC)[1] .     

代谢正常肥胖个体的临床特点及其发生代谢异常性疾病的风险

目的了解代谢正常肥胖（MHO）个体的临床特点并探讨其发生代谢异常性疾病的风险。方法回顾性分析湖南省人民医院体检中心2006年4月至2010年1月体检人群的临床资料,排除资料不全者,共有2830名人员纳入研究。其中1367名于1—3年后再次来院体检。记录受检者临床及生化指标。多组间比较进行方差分析,率的比较用χ2 检验。结果肥胖者占39．58％（1120／2830）,MHO占肥胖者的23．30％（261／1120）。女性MHO的百分比明显高于男性（31．22％比21．64％,χ2=8．126,P〈0．05）。与肥胖伴代谢综合征组比较,MHO组收缩压、舒张压、空腹血糖、甘油三酯、低密度脂蛋白胆固醇（LDL-C）、谷丙转氨酶、尿酸、外周血白细胞计数较低,高密度脂蛋白胆固醇（HDL-C）较高,差异有统计学意义（t值为2．036～20．985,均P〈0．05）;与正常对照组比较,MHO组体质指数、血压、空腹血糖、甘油三酯、LDL—C、谷丙转氨酶、尿酸、外周血白细胞计数较高,HDL．c较低,差异有统计学意义（t值为3．458～10．978,均P〈0．05）。随访1—3年后,正常对照组中有17．6％（44／250）的个体出现代谢异常,而MHO组中46．8％（51／109）出现代谢异常,MHO代谢异常发生风险明显高于正常对照组（OR=4．117,95％CI：2．503—6．770,P〈0．05）。结论MHO个体临床表型介于正常对照与肥胖伴代谢综合征者之间,其发生代谢异常性疾病的风险随时间延长而增加。     

PTEN in liver diseases and cancer

The phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt axis is a key signal transduction node that regulates crucial cellular functions, including insulin and other growth factors signaling, lipid and glucose metabolism, as well as cell survival and apoptosis. In this pathway, PTEN acts as a phosphoinositide phosphatase, which terminates PI3Kpropagated signaling by dephosphorylating PtdIns(3,4)P2 and PtdIns(3,4,5)P3. However, the role of PTEN does not appear to be restricted only to ...     

非酒精性脂肪性肝病脂毒性多臂表型研究进展

正2001年Unger把过量的游离脂肪酸(FFA)由脂肪组织(AT)异位集聚于非AT(NAT)引起细胞损伤现象称为脂肪毒,胰岛素抵抗(IR)和脂凋亡是其两个特征性表型。近来,研究认为脂毒性是NAFLD的多重打击的主轴,其多臂表型介导了NAFLD进展及代谢综合征(MS)发生~([1-5])。此假设日益受到重视,成为当前研究的热点。1 NAFLD是脂毒性肝病1.1脂滴(LD)是脂肪肝(FL)形成的根~([6-8])FL不仅是肝细胞     

脂肪细胞因子和非酒精性脂肪性肝病

本文对脂肪细胞分泌的脂联素、瘦素、抵抗素、内脏脂肪素和炎症因子等在胰岛素抵抗导致非酒精性脂肪性肝病(NAFLD)代谢通路中的多重角色作了系统的综述;阐述了脂源性因子在脂肪组织和肝脏之间的对话机制中介导的代谢综合征和脂肪性肝病之间的关联。     

酒精性肝病的危险因素分析

目的　明确ALD患病率与酒精摄入的量、饮酒的方式习惯、种类及肥胖等的关系。方法　对西安城乡 4115名各种不同职业人群进行整群随机抽样调查及流行病学资料分析。每一调查对象均经调查员上门按统一要求详细询问其饮酒的种类、品牌、度数、时间、频度、方式及饮酒后不良事件的发生次数等 ,必要时还询问其家人 ,以便能更准确的估计其酒精摄入的量。所有饮酒人群均经B超检查 ,并抽取外周血查肝功 ,HBsAg、抗HCV。结果　①每日饮酒精≥ 40g ,持续饮用 5年以上 ,ALD患病率明显增加 ,最高的OR值出现在日酒精消耗量≥ 160g时 ,此时ALD患病率高达 18 7%。而每日饮酒精 <2 0g ,饮酒时间 <5年时 ,无ALD发生。②空腹饮酒者各种酒类的日均消耗量均大于只在进餐时饮酒者 ,空腹单纯饮用白酒和多种酒混合饮用患病率最高 ,分别达18 9%和 15 4%。单纯饮用啤酒等有色酒者ALD发生率较低。③BMI≥ 2 5的 2 0 3例日均酒精消耗量低于BMI <2 5的人群 ,患病率11 5 % ,明显高于人群患病率 6 5 %。结论　日均酒精消耗量 <2 0g ,短于 5年是发生ALD的相对安全域值。日均酒精消耗量 >40g ,>5年则ALD的发病率明显增加 ;空腹饮用白酒和混合饮用多种酒类 ,ALD患病率较高。肥胖者饮酒 ,可增加ALD各阶段发病的危险     

肠道菌群与代谢性疾病研究进展

肠道菌群作为机体“第二基因组”,影响肥胖、糖尿病等代谢性疾病,有重要的病理生理意义。人为改变肠道菌群组分可能是治疗代谢性疾病的新途径。肠道菌群与代谢性疾病的相关性还有待进一步研究。     

中国上海地区40岁以上成人中肥胖与代谢综合征的关系

目的 在中国人中研究肥胖对代谢综合征（ＭＳ）的影响。方法 对５３０例年龄≥４０岁上海地区中国人（男２４４例,女２８６例）检测总体脂〖体重指数（ＢＭＩ）、局部体脂〗腰围（Ｗ）、臀围（Ｈ）、腹腔内脂肪面积（ＶＡ）、腹部皮下脂肪面积（ＳＡ）及股部皮下脂肪面积（ＦＡ）〗、体脂分布〖Ｗ与Ｈ比（ＷＨＲ）及（ＶＡ＋ＳＡ）／ＦＡ〗及胰岛素敏感性（ＨＯＭＡ－ＩＲ）。以单变量及多变量分析方法观察体脂、胰岛素抵抗与ＭＳ     

Therapeutic liver repopulation for metabolic liver diseases: Advances from bench to bedside

Metabolic liver diseases are characterized by inherited defects in hepatic enzymes or other proteins with metabolic functions. Therapeutic liver repopulation (TLR), an approach of massive liver replacement by transplanted normal hepatocytes, could be used to provide the missing metabolic function elegantly. However, partial and transient correction of the underlying metabolic defects due to very few integrated donor cell mass remains the major obstacle for the effective and widespread use of this approach. Little engraftment and proliferation insufficiency lead to the poor outcome. This article reviews the advances in the mechanisms of initial engraftment and selective proliferation and suggests some effective treatment strategies, from pharmacological preconditioning to stem cell transplantation, to optimize liver repopulation with liver cell transplantation. Enhancing cell viability and plating efficiency, increasing sinusoidal spaces, regulation of sinusoidal endothelial cell barrier and controlling inflammatory reaction may promote initial cell engraftment. Liver‐directed irradiation, reversible portal vein embolization and fetal liver stem/progenitor cell transplantation induce preferential proliferation of donor cells substantially without severe side‐effects. Furthermore, it seems better to use combined approaches to achieve a high level of liver repopulation for the management of metabolic liver diseases.     

Brain-gut-liver interactions across the spectrum of insulin resistance in metabolic fatty liver disease

Metabolic associated fatty liver disease (MAFLD), formerly named “nonalcoholic fatty liver disease” occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity and mortality risk factor for major causes of death, such as cardiovascular, digestive, metabolic, neoplastic and neuro-degenerative diseases. However, progression of MAFLD and its associated systemic complications occur almost invariably in patients who experience the additional burden of intrahepatic and/or systemic inflammation, which acts as disease accelerator. Our review is focused on the new knowledge about the brain-gut-liver axis in the context of metabolic dysregulations associated with fatty liver, where insulin resistance has been assumed to play an important role. Special emphasis has been given to digital imaging studies and in particular to positron emission tomography, as it represents a unique opportunity for the noninvasive in vivo study of tissue metabolism. An exhaustive revision of targeted animal models is also provided in order to clarify what the available preclinical evidence suggests for the causal interactions between fatty liver, dysregulated endogenous glucose production and insulin resistance.     

甘油三酯-葡萄糖指数与胰岛素抵抗相关代谢性疾病的关系

胰岛素抵抗在2型糖尿病、冠状动脉粥样硬化、非酒精性脂肪性肝病、代谢综合征等代谢紊乱性疾病的发生发展中均起着重要作用。诸多研究已表明,甘油三酯-葡萄糖(triglyceride glucose,TyG)指数可作为评估胰岛素抵抗的代谢指标,与胰岛素抵抗及其相关代谢性疾病之间存在着不同程度的联系。因此,本综述重点阐述TyG指...     

酒精性肝病与代谢综合征

长期持续大量饮酒不仅直接导致终末期肝硬化或肝癌的发生,还可以影响肝脏的代谢而出现代谢综合征(MS)。众多研究表明,酗酒可增加MS的危险性,后者可发展为肝性糖尿病、高血压和冠心病,并增加这些疾病的死亡率。研究表明,相对于没有或者偶尔饮酒,适度饮酒的人群高血压和2型糖尿病的患病率较低。事实并非如此,饮酒与MS各组分之间存在着保护、有害或J型的复杂机制。因此,本文回顾了饮酒与MS组分的关系,并讨论了酒精合理的潜在的生物学机制,以期引起临床和研究的注意。     

合并MAFLD的乙型肝炎肝硬化患者血清瘦素水平变化特点分析

目的 探讨合并代谢相关脂肪性肝病(MAFLD)的乙型肝炎肝硬化患者血清瘦素(LP)水平变化特点.方法 在我院中法肝癌项目收集的标本库中,选择186例乙型肝炎肝硬化患者(Child-Pugh A级95例,B级51例和C级40例),在Child-Pugh A级患者中,合并MAFLD患者49例,未合并46例.采用ELISA法...     

Neck circumference and metabolic syndrome: A cross-sectional population-based study

ObjectivesThis study aimed to investigate the possible association of neck circumference with cardiometabolic risk factors, and to find out the possible cutoff points of neck circumference for the diagnosis of metabolic syndrome among the Iranian population.MethodThis is a cross-sectional study in 1619 participants who were selected through clustered random sampling, as a part of a health cohort in Amol, Iran. Diagnosis of metabolic syndrome (MetS) was based on the modified criteria of the National Cholesterol Educational Program Adult Treatment Panel (NCEP ATP III). Associations of neck circumference with Mets and its components were studied using logistic regression. The optimal cutoff point of neck circumference for MetS diagnosis was calculated based on the Youden index.ResultsMetabolic syndrome was diagnosed in 433 (26.7%) of patients. Neck circumference was shown to be significantly associated with central obesity, hypertension, hypertriglyceridemia, impaired fasting glucose, and low serum high-density lipoprotein (HDL) level, as well as MetS. The optimal cutoff points of neck circumference in the diagnosis of MetS are 36 cm and 42 cm for women and men, respectively. Sensitivity of the optimal cut-off point of NC for diagnosing patients with MetS was higher in women compared to men (70.6% compared to 55.9%).ConclusionA significant association was observed between neck circumference and the presence of MetS among the Iranian population and neck circumference can be offered as a new index in screening and diagnosis for MetS and assessing cardiometabolic risk factors.     

非酒精性脂肪肝:代谢综合征的另一个特征

目的　分析非酒精性脂肪肝 (NAFL)临床及生化特征 ,以探讨NAFL可否成为代谢综合征的一个组成部分。方法　对 85例NAFL患者测体重指数、腰臀比、空腹血糖、血脂、胰岛素、餐后 2h血糖和胰岛素抵抗指数。以 43例非脂肪肝的体检者为对照组。结果　 1.在NAFL患者中 ,中心性肥胖占 70 .5 9% ,高血压病占 3 1.77% ,高TG血症占 62 .3 5 % ,低HDL C占 3 6.47% ,均明显高于对照组 (P <0 .0 0 5～ 0 .0 1) ,而DM/IGT/IPG的患病率 ,两组相比无明显差异 ;2 .血清FINS水平和IR脂肪肝组也较对照组明显增加 (P <0 .0 1) ;3 .在 12 8例研究对象中 ,有 2 1例患者患有代谢综合征 ,其中脂肪肝者占 85 .71% ,中心性肥胖者占 90 .48% ,高血压者占 76.19% ,血脂紊乱者占 10 0 % ,DM/IGT/IPG者占 3 8.10 %。结论　NAFL患者存在明显的胰岛素抵抗 ,可作为代谢综合征的一个组成部分。     

Liver transplantation and non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis (nonalcoholic steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance (or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following: (1) the increasing need for liver transplantation due to NASH; (2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation; (3) the long term graft and patient outcomes after liver transplantation for NASH, and finally; and (4) the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.     

Low levels of Lysosomal Acid Lipase (LAL) activity increases necroinflammation in adult patients with biopsy-proven metabolic associated fatty liver disease

Introduction and objectiveMetabolic associated fatty liver disease (MAFLD), characterized by intra-hepatic fat accumulation, will soon be the leading cause of end-stage liver disease. Lysosomal Acid Lipase (LAL) is a key enzyme in lipid metabolism. We investigated its activity in patients with biopsy-proven MAFLD.MethodsProspective cross-sectional study in patients with biopsy-proven MAFLD. Blood LAL-activity (pmol/punch/h) was measured with dried blood spot extracts using Lalistat 2. Demographic, clinical, and laboratory data were collected.Results101 adult patients were recruited. Among them, 11.9% had a diagnosis of MAFLD without steatohepatitis and 88.1% had MAFLD with steatohepatitis. The median of LAL-activity in patients with MAFLD was 76.8 pmol/punch/h. MAFLD patients with steatohepatitis showed an increase in gamma-glutamyl transferase (p = 0.042), insulin (p = 0.001), homeostatic model assessment for insulin resistance (HOMA-IR, p = 0.001) and advanced liver fibrosis (p < 0.001), compared to cases of MAFLD without steatohepatitis. There was no statistical difference in LAL-activity between the cases (p = 0.296). When considering LAL-activity above and below 77 pmol/punch/h as a cut-off value, patients with reduced LAL-activity had a significant increase in necroinflammatory activity according to the METAVIR score (p = 0.040), and NAFLD activity score (NAS, p = 0.031) compared to cases with higher LAL-activity.ConclusionOur findings suggest that reduced LAL-activity is associated with increased necroinflammatory activity and severity of the NAS. A better knowledge of the role of LAL may provide new insights into the pathogenesis and progression of MAFLD.     

武汉市离退休老年人非酒精性脂肪肝及代谢综合征的相关性研究

目的 了解武汉市离退休老年人群非酒精性脂肪肝和代谢综合征的现况特点及2种疾病的相关性. 方法 抽样调查60岁及以上离退休老年人共718例,检测身高、体质量、腰围、血压、血糖、血脂、肝脏B超. 结果 所调查人群代谢综合征及非酒精性脂肪肝的患病率分别为25.2%及25.9%,而高血压、高血糖、高三酰甘油、低高密度脂蛋白胆固醇及腹型肥胖的患病率分别为89.2%,29.6%,40.3%,10.3%及38.6%;女性代谢综合征患病率高于男性(χ2=21.0,P<0.05);随着代谢综合征中异常组分的数目增多,非酒精性脂肪肝的患病率亦增加(男性χ2=82.9,女性χ2=23.7,均为P<0.01);老年人非酒精性脂肪肝患病率与代谢综合征呈显著正相关(男性OR=2.216,女性OR=4.848,均为P<0.01). 结论 离退休老年人群非酒精性脂肪肝及代谢综合征患病率较高,并且两者显著相关,应积极防治心血管疾病高危因子.     

非酒精性脂肪性肝病与代谢综合征

非酒精性脂肪性肝病(NAFLD)是一种包括从单纯的肝脂肪变性到非酒精性脂肪性肝炎,以致最终发展为肝硬化的一组肝脏慢性广谱性临床病理综合征。近年来大量研究表明,NAFLD与代谢综合征(MS)的各个组分密切伴随,甚至有学者将其作为MS的组分之一,并发现胰岛素抵抗在NAFLD发病机制中起关键作用。迄今对NAFLD的发病机制还了解甚少,目前广泛接受的一个理论是“二次打击”假说。脂肪酸和甘油三酯在肝脏沉积造成的“第一次打击”之后,肝细胞对氧化应激和炎症因子作用导致的“第二次打击”的敏感性增加而引起肝损害。本文主要目的是对NAFLD的临床病理特点、与胰岛素抵抗及MS的关系以及可能的分子机制进行综述,同时也介绍了目前预防和治疗NAFLD的策略。     

不同病理学类型肺癌患者合并代谢综合征和非酒精性脂肪性肝病发生率调查*

目的 探讨肺癌患者代谢综合征（MetS）和非酒精性脂肪性肝病（NAFLD）的患病率。方法 回顾性分析2013年上海市肺科医院经病理学确诊的肺癌患者的临床资料,使用日立700全自动生化分析仪检测血生化指标,使用美国GE公司高档Vivid7 彩色多普勒超声诊断仪或美国西门子公司SONOLINE G50彩色多普勒超声诊断仪诊断NAFLD。结果 在675例肺癌患者中,男性391例（57.9%）,女性284例（42.1%）,平均年龄（59.7±9.71）岁。其中165例（24.4%）患者合并MetS;在148例鳞癌、456例腺癌、11例小细胞肺癌、60例其他病理类型患者中,分别有33例（22.3%）、117例 （25.7%）、2例（18.2%）、13 例(21.7%)患者合并MetS,不同病理类型的肺癌患者之间MetS患病率无显著统计学差异（x2=1.244,P=0.743）;148例鳞癌与456例腺癌患者合并肥胖症、低HDL血症、高血糖和高血压百分比无显著性相差,仅腺癌患者合并高TG血症百分比显著高于鳞癌患者（25.4%对17.4%,P=0.046）;456例腺癌与219例非腺癌患者合并MetS或NAFLD百分比均无显著性相差（P>0.05）。结论 高TG血症和NAFLD可能与肺腺癌的发生相关。