解读非酒精性脂肪性肝病诊治指南

随着肥胖与糖尿病患者的日趋增多,脂肪性肝病(FLD)目前已成为全球性的重要肝病。临床上FLD分为酒精性肝病(ALD)与非酒精性脂肪性肝病(NAFLD);研究表明,NAFLD与肥胖、代谢综合征、2型糖尿病和心血管疾病密切相关。2006年和2010年中华医学会相继制定了中国NAFLD诊疗指南,较全面和广泛地反映了目前NAFLD的临床诊疗现状,与国际上颁布的一些诊治指南相比存在差异。本文就NAFLD诊治指南及相关问题进行解读。     

代谢相关脂肪性肝病自然史研究进展

<正>非酒精性脂肪性肝病(non-alcoholic fatty liverdiseases,NAFLD)是由于遗传易感个体营养过剩和代谢功能障碍引起的脂肪性肝病,现被更名为代谢相关性脂肪性肝病(metabolic dysfunction-associatedfatty liver diseases,MAFLD,或metabolic dysfunction-associated steatotic liver diseases, MASLD)^[1-3]。超重/肥胖、 2型糖尿病(type 2 diabetes mellitus,T2DM)、代谢综合征是NAFLD的重要危险因素,并且NAFLD与代谢功能障碍互为因果。代谢综合征是NAFLD患者全因死亡、肝脏相关死亡和动脉硬化性心血管疾病(cardiovascular disease,CVD)相关死亡的独立预测指标,而不伴代谢紊乱的NAFLD患者预后与无肝病患者的普通人群相同^[4,5]。本文介绍了NAFLD/MAFLD/MASLD患者在自然转归方面的研究进展,旨在为脂肪性肝病患者的随访...     

甲状腺功能正常的原发性高血压患者甲状腺激素水平与非酒精性脂肪性肝病的关系研究

目的 探讨甲状腺功能正常的原发性高血压(EH)患者甲状腺激素水平与非酒精性脂肪性肝病(NAFLD)的关系。方法 回顾性选取2019年在延安大学咸阳医院心血管内科住院的甲状腺功能正常的EH患者395例。根据患者是否发生NAFLD,将其分为NAFLD组(n=185)和非NAFLD组(n=210)。收集患者临床资料,采用多因素Logistic回归分析探讨甲状腺功能正常的EH患者发生NAFLD的影响因素。结果 NAFLD组患者年龄小于非NAFLD组,BMI及三酰甘油(TG)、血尿酸(SUA)、空腹血糖(FPG)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、γ-谷氨酰转移酶(γ-GT)、促甲状腺激素(TSH)、游离三碘甲状腺原氨酸(FT₃)水平高于非NAFLD组,高密度脂蛋白胆固醇(HDL-C)水平低于非NAFLD组(P<0.05)。多因素Logistic回归分析结果显示,BMI〔OR=1.283,95%CI(1.182,1.392)〕及TG〔OR=1.460,95%CI(1.104,1.931)〕、SUA〔OR=1.007,95%CI(1.003,1....     

甲状腺激素水平与非酒精性脂肪性肝病发生的关系

目的探讨甲状腺激素水平与非酒精性脂肪性肝病(NAFLD)发生的关系。方法回顾性分析2015年7月—2019年4月在中国人民解放军火箭军特色医学中心体检人群3289例临床资料,根据病史及甲状腺功能分为亚临床甲状腺功能减退组(n=210)及甲状腺功能正常组(n=3079)。将甲状腺功能正常组根据腹部彩超结果分为NAFLD组(n=516)及非NAFLD组(n=2563);根据BMI划分为非肥胖亚组(BMI 25 kg/m2)、肥胖亚组(BMI≥25 kg/m2);根据年龄划分为老年组(≥60岁)、中青年组(60岁)。对甲状腺功能正常组进行不同年龄层、不同体型亚组分型。收集性别、年龄、BMI、血压、腰围、空腹血糖、尿酸、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、游离三碘甲状腺原氨酸、游离甲状腺素、三碘甲状腺原氨酸、甲状腺素、促甲状腺激素指标。符合正态分布的计量资料2组间比较采用两独立样本t检验,非正态分布的计量资料2组间比较采用Mann-Whitney U检验,计数资料2组间比较采用χ~2检验,危险因素分析采用多因素logistic回归分析,应用受试者工作特征曲线(ROC曲线)分析所观察指标预测NAFLD发生的临界值。结果亚临床甲状腺功能减退组NAFLD患病率高于甲状腺功能正常组(22.38%vs 16.76%,χ~2=4.380,P=0.036),亚临床甲状腺功能减退组NAFLD患者促甲状腺激素水平高于非NAFLD患者(Z=-1.994,P=0.046)。甲状腺功能正常组甲状腺各参数水平在NAFLD组与非NAFLD组间差异无统计学意义(P值均 0.05),但进行年龄、体型分层后,肥胖-中青年亚组中,男性、低游离甲状腺素、空腹血糖、甘油三酯是NAFLD发生的独立危险因素(比值比分别为4.729、0.067、1.814、1.717,P值分别为0.003、0.010、0.011、0.014)。游离甲状腺素、空腹血糖、甘油三酯预测NAFLD的临界值分别为1.123 ng/d L、5.15 mmol/L、1.02 mmol/L,联合预测ROC曲线下面积为0.832。结论亚临床甲状腺功能减退人群NAFLD患病率高;甲状腺素水平在正常范围内时,低游离甲状腺素水平与中青年肥胖人群NAFLD的发生有关。     

从非酒精性脂肪性肝病到代谢相关脂肪性肝病的变迁

非酒精性脂肪性肝病(NAFLD)是全球范围最常见的慢性肝病,且进展至肝纤维化、肝硬化、肝癌等不良结局加重社会医疗负担。NAFLD特征是肝脏脂肪沉积和炎症,近40余年以来一直是一个排他性诊断,随着研究不断地深入,2020至2023年期间经历了两次更名,从代谢相关脂肪性肝病(MAFLD)到代谢功能障碍相关脂肪性肝病(MASLD)。本文讨论了目前对NAFLD/MAFLD/MASLD特征的对比、临床和研究问题,旨在提高我们对脂肪性肝病(SLD)的全面理解。     

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。     

酒精性与非酒精性脂肪性肝病

脂肪性肝病(FLD)根据有无过量饮酒史,分为酒精性肝病(ALD)和非酒精性脂肪性肝病(NAFLD)两大类。两者享有FLD的许多共性特征,但又各有其独特之处。 1.酒精性与非酒精性FLD的异同:NAFLD的肝组织学改变与ALD相似,包括单纯性脂肪肝、脂肪性肝炎及肝硬化。我国及日本学者认为ALD还应包括轻症ALD、酒精性重型肝炎及酒精性肝纤维化,事实上NAFLD均有其相对应的临床病理类     

脂肪性肝病研究新进展

<正>脂肪性肝病包括酒精性脂肪性肝病(ALD)和非酒精性脂肪性肝病(NAFLD)两大类。ALD包括单纯性脂肪肝、酒精性肝炎、酒精性肝纤维化及肝硬化;NAFLD包括单纯性脂肪肝(NAFL)、非酒精性脂肪肝性肝炎(NASH)、非酒精性脂肪性肝纤维化及肝硬化等。目前,全球脂肪性肝病的发病率逐年增多,尤其以发达国家和地区为甚。NAFLD还与2型糖尿病、心血管疾病、代谢综合征等疾病密切相     

非酒精性脂肪性肝病更名的临床意义

非酒精性脂肪性肝炎和非酒精性脂肪性肝病(NAFLD)在20世纪80年代首次用于描述肝组织学改变与酒精性肝病相似但患者无过量饮酒且无其他损肝因素存在。40年来,NAFLD的研究越来越深入且进展迅速。然而,一直未变的NAFLD命名对日常临床实践和当前临床试验已产生了一定的阻碍。为了克服旧术语的缺陷,日前国际共识小组建议应用代谢相关脂肪性肝病(MAFLD)取代NAFLD,并进一步提出既全面又简便的MAFLD新定义用于临床诊断,从而使MAFLD有别于其他肝脏疾病;同时,建议MAFLD的疾病评估和严重程度分层应该超出当前的二分类法则。NAFLD更名为MAFLD将成为优化临床实践,提高临床研究效率,并使医生、患者群体获益的一项重要举措。     

镇江地区非酒精性脂肪性肝病患病情况及与幽门螺杆菌感染的相关性

目的探讨镇江地区非酒精性脂肪性肝病(NAFLD)患病情况及其与幽门螺杆菌(HP)感染的相关性。方法选取体检者43 216人为研究对象,进行13C-尿素呼吸试验检测、腹部超声检测及相关生化指标检测,分析NAFLD患病及HP感染情况。结果 NAFLD患病率为31.00%,HP感染率为21.99%。HP感染者NAFLD患病率显著高于非感染者(P<0.001);NAFLD患病人群HP感染率显著高于非NAFLD患者(P<0.001)。BMI异常、高血压和HP感染为影响本地区体检人群NAFLD患病的显著危险因素(均P<0.05)。NAFLD患病率与患者中HP感染率呈显著正相关(r=0.821,P<0.001)。结论镇江地区NAFLD患病率较高,且逐年升高,HP感染为NAFLD发生的危险因素。     

Cross-talk between the thyroid and liver:A new target for nonalcoholic fatty liver disease treatment

Nonalcoholic fatty liver disease(NAFLD)has been recognized as the most common liver metabolic disease,and it is also a burgeoning health problem that affects one-third of adults and is associated with obesity and insulin resistance now.Thyroid hormone(TH)and its receptors play a fundamental role in lipid metabolism and lipid accumulation in the liver.It is found that thyroid receptor and its isoforms exhibit tissue-specific expression with a variety of functions.TRβ1 is predominantly expressed in the brain and adipose tissue and TRβ2 is the major isoform in the liver,kidney and fat.They have different functions and play important roles in lipid metabolism.Recently,there are many studies on the treatment of NAFLD with TH and its analogues.We review here that thyroid hormone and TR are a potential target for pharmacologic treatments.Lipid metabolism and lipid accumulation can be regulated and reversed by TH and its analogues.     

Thyroid hormone analogues and derivatives:Actions in fatty liver

Fatty liver or nonalcoholic fatty liver disease(NAFLD),a problem of increasing clinical significance and prevalence worldwide,is associated with increased risk for the development of cirrhosis and hepatocellular carcinoma.Although several therapeutic approaches can be used in the context of NAFLD,dietary and physical activities are still the most frequently used strategies.Some pharmacological agents show promising results although no conclusions can be drawn from recent clinical trials.Thyroid hormones[THs;thyroxine(T4)and3,3′,5-triiodo-L-thyronine(T3)]coordinate a diverse array of physiological events during development and lipid/energy homeostasis and have some potentially therapeutic actions which include inducing weight loss,and lowering plasma cholesterol levels and tissue adiposity.The thyroid hormones exert their physiological effects by binding to specific nuclear receptors[thyroid hormone receptors(TR)]of which the TRβisoform is liver specific and has been considered a putative target for the treatment of dyslipidemia and fatty liver.In view of this,the aim of the review is(1)to provide an overview of the action of T3 on lipid metabolism with implications for liver steatosis and(2)to provide an update on the current knowledge concerning the administration of TRβselective thyromimetics(GC-1 and MB07811),as well as of 3,5-diiodo-L-thyronine and its novel functional analogue TRC150094 in animal models of overweight and related disorders including primarily fatty liver.     

NAFLD合并T2DM患者糖化血红蛋白和甲状腺激素水平的变化及其临床意义*

目的 探讨非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者糖化血红蛋白(HbA1C)和甲状腺激素水平的变化及其临床意义。方法 2017年4月～2019年3月我院内分泌科就诊的T2DM患者50例和NAFLD合并T2DM患者55例,检测人体学指标,采用电化学发光法检测空腹胰岛素(FINS)水平,采用胶体金法检测血糖化血红蛋白(HbA1C)水平,采用化学发光免疫分析法测定血清游离三碘甲状腺原氨酸(FT3)、游离四碘甲状腺原氨酸(FT4)和促甲状腺激素(TSH)水平。结果 NAFLD合并T2DM患者体质指数(BMI)为(28.4±2.7)kg/m²,显著大于T2DM患者【(24.0±2.4)kg/m²,P<0.05】,NAFLD合并T2DM患者腰围为(94.5±8.5)cm,显著大于T2DM患者【(84.0±7.6)cm,P<0.05】,NAFLD合并T2DM患者臀围为(97.1±8.0)cm,显著大于T2DM患者【(89.7±7.2)cm,P<0.05】;NAFLD合并T2DM患者血清谷丙转氨酶(ALT)水平为(79.5±7.6)U/L,显著高于T2DM患者【(42.3±4.3)U/L,P<0.05】,NAFLD合并T2DM患者血清谷草转氨酶(AST)水平为(59.7±6.1)U/L,显著高于T2DM患者【(41.2±3.9)U/L,P<0.05】,NAFLD合并T2DM患者血清谷氨酰转肽酶(GGT)水平为(105.8±9.4)U/L,显著高于T2DM患者【(60.9±6.5)U/L,P<0.05】;NAFLD合并T2DM患者血甘油三酯(TG)水平为(4.2±1.7) mmol/L,显著高于T2DM患者【(2.4±0.9)mmol/L,P<0.05】,NAFLD合并T2DM患者空腹血胰岛素(FINS)水平为(12.0±2.5)mU/L,显著大于T2DM患者【(9.1±1.8)mU/L,P<0.05】;NAFLD合并T2DM患者血清TSH水平为(3.4±1.2)mU/L,显著大于T2DM患者【(1.9±0.8)mU/L,P<0.05】,而两组FT3和FT4水平无显著性差异(P>0.05)。结论 NAFLD合并T2DM患者BMI、肝功能指标、TG、FINS和TSH水平均显著增大或升高,与T2DM患者有明显的不同,在临床诊治过程中应当有所甄别,深入研究NAFLD患者发病机制对诊治将大有裨益。     

非酒精性脂肪肝血尿酸水平与胰岛素抵抗的相关性

目的:研究非酒精性脂肪肝(non-alcoholic fatty liver,NAFL)患者血尿酸水平及其与胰岛素抵抗程度的相关性.方法:选取单纯NAFL患者40例,NAFL合并2型糖尿病患者(type2diabetes mellitus,T2DM)72例,健康体检者62名为研究对象.测定体重指数(body mass index,BMI),检测空腹血糖(fasting blood glucose,FBG)、尿酸(serum uric acid,SUA)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、胆固醇(cholesterol,TC)、甘油三酯(triglyceride,TG)、糖化血红蛋白(glycated hemoglobin,HbA1C)、尿微量白蛋白/尿肌酐(Ualb/UCr)等生化指标并行肝脏B超检查.放射免疫法测定空腹胰岛素(fasting insulin,FINS),计算胰岛素抵抗指数(HOMA IR).结果:NAFL合并T2DM组BMI、SUA、ALT、AST、TG、FBG、FINS、HOMA IR、HbA1C、Ualb/UCr、SF均高于对照组;与单纯NAFL比较,NAFL合并T2DM组胰岛素抵抗及SUA水平更重;相关性研究表明FBG、HOMA IR、HbA1C与SUA呈正相关.结论:NAFL患者存在明显的胰岛素抵抗及高血尿酸血症,且两者具有一定的相关性.降低胰岛素抵抗联合纠正尿酸代谢紊乱对防止NAFL的发生发展具有重要的临床意义.     

肝移植术后新发非酒精性脂肪肝的危险因素

目的探究肝移植术后新发非酒精性脂肪肝(non-alcoholic fatty liver disease NAFLD)的危险因素。方法收集2015年5月至2019年5月于解放军总医院第五医学中心136例行肝移植患者的临床资料。比较移植术后新发NAFLD患者与无NAFLD患者的临床资料。应用logistic回归分析移植术后新发NAFLD的危险因素。结果肝移植术后1年时新发NAFLD的发病率为11.03%(15/136)。新发NAFLD患者与无NAFLD患者比较,术前BMI(27.85比23.17,P=0.003)、酒精性肝硬化(66.7%比23.1%,P=0.001)、术前高血压病史(33.3%比5.4%,P=0.016),肝移植术后1年时的ALT水平(24.0 U/L比21.5 U/L,P=0.012)差异有统计学意义。Logistic回归分析结果显示,术前酒精性肝硬化(OR=4.79,95%CI:1.35~16.98)、术前高BMI(OR=1.23,95%CI:1.05~1.46)是术后新发NAFLD的危险因素。结论肝移植术前酒精性肝硬化和高BMI是术后新发NAFLD的危险因素。     

非酒精性脂肪性肝病合并2型糖尿病患者血浆促甲状腺激素水平变化及其临床意义*

目的 研究非酒精性脂肪性肝病（NAFLD）合并2型糖尿病（T2DM）患者血清促甲状腺激素（TSH）水平的变化及其临床意义。方法 纳入NAFLD合并T2DM患者43例和T2DM患者40例,比较两组年龄、性别、身高、体质指数（BMI）、血压和血生化指标及血清糖化血红蛋白（HbAlc）、空腹胰岛素（FINS）、游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）等指标的差异,采用Logistic回归分析影响NAFLD患者发生T2DM的独立危险因素。结果 NAFLD合并T2DM患者体质指数（BMI）为（28.4±3.8） kg/m²,显著大于T2DM患者的（23.8±3.1） kg/m²,P<0.05）; NAFLD合并T2DM患者血清ALT、AST、GGT、TG、HOMA-IR和TSH水平显著高于T2DM患者（P<0.05）;不同血清TSH的NAFLD患者血清TC、TG、LDL-C和FT3水平存在显著性差异（P<0.05）;经Logistic回归分析显示,BMI（RR=1.720,95%CI为1.154~3.015）、HOMA-IR（RR=2.632,95%CI为1.010~3.654）、血清TSH（RR=2.577,95%CI为1.214~3.689）和TG水平（RR=1.538,95%CI为1.240~2.658）是影响NAFLD患者发生T2DM的独立危险因素。结论 了解NAFLD患者发生T2DM的危险因素有助于早期预防和干预,检测血清TSH水平可能对筛查合并T2DM的NAFLD患者有一定的临床意义。     

氧化应激与核因子E2相关因子2在非酒精性脂肪性肝病中的作用

非酒精性脂肪肝病(NAFLD)是全球最流行的慢性肝病,发病率逐年上升。氧化应激是非酒精性脂肪肝病经典“二次打击”发病机制的第二次打击,是目前公认的NAFLD发病机制之一。核因子E2相关因子2(Nrf2)是保护肝细胞免受氧化应激的一组正向调节因子,是细胞抗氧化应激的关键因子,也是拮抗肝脏氧化应激的关键转录因子,在NAFLD发生发展中起重要作用,Nrf2可能是改善NAFLD的潜在治疗靶点。对氧化应激及Nrf2通路在NAFLD中的发病机制进行了综述。     

Mean platelet volume in biopsy-proven non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as the most common cause of chronic liver disease worldwide. It has been shown that NAFLD has a strong association with metabolic syndrome and its component like insulin resistance (IR). Cardiovascular disease has a relation with NAFLD. Platelet volume is an indicator of platelet function and activation. Mean platelet volume (MPV) has been reported as a risk factor for atherothrombosis. In our study, we aimed to investigate the relation of MPV with NAFLD and IR in the NAFLD patients. A total of 54 patients with histologically proven NAFLD and 41 healthy age-matched control subject were enrolled in this study. The NAFLD subjects were divided into two subgroups: 42 patients in the insulin resistant group (median age 39.5, females 22 [52%]) and 12 patients in the insulin sensitive group (median age 38, females 5 [41.7%]). MPV were significantly higher in the NAFLD group in univariate analysis (p?<?0.05). In the NAFLD patients, we did not find any relation between steatosis grade, lobular inflammation, hepatocellular ballooning, NAFLD activity score and fibrosis with MPV value. Among the insulin resistant and sensitive groups in the NAFLD patients MPV values were similar. The results of this study showed that MPV, an indicator of platelet activation, increased in biopsy proven NAFLD patients but MPV is not correlated with the increase of IR in NAFLD patients. MPV is not related with inflammation and steatosis degree, hepatocellular ballooning and fibrosis in NAFLD patients.     

The Association of Metabolic Syndrome, Insulin Resistance and Non-alcoholic Fatty Liver Disease in Overweight/Obese Children

Background/Aim:

To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT).

Patients and Methods:

Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy.

Results:

Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%).

Conclusion:

There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.     

Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease:Potential mechanistic pathways

Although hepatocellular carcinoma(HCC) primarily arises in the background of liver cirrhosis,the development of HCC in nonalcoholic fatty liver disease(NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome(MS) along with obesity and insulin resistance(IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS,NAFLD,and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6,leptin and resistin,as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver,which precede HCC development. Nevertheless,further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.