脂肪肝

非酒精性脂肪性肝病临床和病理学研究——郑瑞丹等（福建漳州解放军第175医院肝病治疗中心363000）；《中华肝脏病杂志》，2006，14（6）：449—452[目的：研究非酒精性脂肪性肝病（NAFLD）的临床与病理特征。方法：分析41例NAFLD患者的肝组织脂肪变程度、炎症分级和纤维化分期，并研究其与体重指数（BMI）、血清生物化学和B超检查结果的关系。     

中药治疗非酒精性脂肪性肝纤维化的研究现状

非酒精性脂肪性肝纤维化是非酒精性脂肪性肝炎（NASH）进展为终末期肝病的关键病理阶段,其有效治疗亟待解决。中药具有多组分及多途径、多靶点作用的特点,对非酒精性脂肪性肝纤维化具有综合治疗的优势,可通过调节肝脏脂质代谢、抑制氧化应激反应及肝细胞凋亡、调节炎症、纤维化相关基因的表达等阻止肝脂肪变、炎症及纤维化的发生与进展。     

非酒精性脂肪性肝病对慢性乙肝患者肝脏炎症及纤维化程度的影响

目的探讨非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）对慢性乙肝（chronic hepatitis B,CHB）患者肝脏炎症及纤维化程度的影响。方法收集2006年1月~2010年6月间住院资料完整的慢性乙肝患者147例,按照是否合并非酒精性脂肪性肝病分为A、B两组,回顾性分析两组间年龄、性别、肝功能指标、肝纤维化酶谱、HBsAg水平、HBV DNA滴度、代谢综合征相关疾病的患病率、肝脏炎症和纤维化程度等。结果 A组患者肝纤维化酶谱、碱性磷酸酶、代谢综合征相关疾病的患病率较B组升高;A组患者的肝纤维化程度主要分布在S2、S3期,而B组患者的肝纤维化程度主要分布在S0-1、S2期,余指标无差异。结论非酒精性脂肪性肝病对慢性乙肝患者肝脏炎症无明显影响,但能促进慢性乙肝患者肝纤维化的发展。     

代谢综合征与慢性乙型病毒性肝炎及非酒精性脂肪性肝病患者肝纤维化程度的相关性研究

目的 比较慢性乙型病毒性肝炎患者和非酒精性脂肪性肝病患者代谢综合征患病率,以及代谢综合征对慢性乙型病毒性肝炎患者和非酒精性脂肪性肝病患者肝纤维化进展的影响.方法 对2008年1月至2009年6月在我院就诊的136例慢性乙型病毒性肝炎患者和110例非酒精性脂肪性肝病患者进行回顾性分析,调查其代谢综合征的患病率,测定肝功能及病毒学指标,进行肝脏病理学检查.采用t检验和X~2检验进行统计学分析.结果 代谢综合征总的患病率为28.5%,非酒精性脂肪性肝病患者代谢综合征患病率显著高于慢性乙型病毒性肝炎患者(分别为49.1%和11.8%).肝纤维化分期为S_(0～1)、S_(2～4)的慢性乙型病毒性肝炎患者代谢综合征的患病率分别为3.1%和19.7%(P＜0.01),代谢综合征、体重指数、天门冬氨酸转氨酶、γ-谷氨酰转肽酶及炎症程度均与其肝纤维化程度相关.在非酒精性脂肪性肝病患者中,非酒精性脂肪性肝炎患者代谢综合征患者率高于非酒精性脂肪肝(分别为55.4%和40.0%);纤维化分期为S_(0～1)、S_(2～4)的患者代谢综合征的患病率分别为36.2%和70.7%(P＜0.01);代谢综合征、丙氨酸转氨酶、天门冬氨酸转氨酶、γ-谷氨酰转肽酶及明显炎症均与其肝纤维化严重程度相关.结论 非酒精性脂肪性肝病患者代谢综合征的患病率高于慢性乙型病毒性肝炎患者,这两类患者代谢综合征与肝纤维化程度相关.     

血管内皮生长因子与非酒精性脂肪性肝病

非酒精性脂肪性肝病（NAFLD）是影响公共健康的全球性疾病,其病理变化可向非酒精性单纯性脂肪肝（NAFL）、脂肪性肝炎（NASH）甚至脂肪性肝硬化（FLC）发展。虽然NAFLD的这些病理进展机制尚未明确,但仍有一些实验研究提示了可能的诱发机制。其中血管内皮生长因子（VEGF）在促进NAFLD肝脏炎症、肝纤维化中发挥着重要的作用。本文就VEGF与NAFLD关系的研究进展予以综述。     

强肝胶囊治疗非酒精性脂肪性肝纤维化的临床研究

目的：观察强肝胶囊治疗非酒精性脂肪性肝纤维化的疗效。方法：将104例非酒精性脂肪性肝纤维化患者随机分为两组。对照组40例进行基础护肝治疗,治疗组64例在此基础上加用强肝胶囊治疗,疗程均为6个月,观察治疗前后的临床症状、肝功能、肝纤维化谱、肝脏B超、肝脏MR扩散加权成像及肝脏病理情况。结果：治疗组患者治疗前后比较,其临床症状缓解,肝功能恢复,肝纤维化谱、肝脏B超、肝脏MR扩散加权成像及肝脏病理均显示出肝脏纤维化程度明显减轻,差异有显著性意义（P〈0.05）。治疗组与对照组治疗后比较肝纤维化程度明显改善,差异有显著性意义（P〈0.05）。结论：强肝胶囊不仅改善患者临床症状及肝功能,而且具有明显的改善肝脏纤维化程度的作用,是治疗非酒精性脂肪性肝纤维化的有效药物之一。     

非酒精性脂肪肝的研究进展

非酒精性脂肪肝（NAFLD）是一种无过量饮酒史，但病理学改变类似酒精性脂肪性肝病（AFLD），以肝细胞脂肪变性和脂质贮积为特征的临床病理综合征。其疾病谱包括单纯性脂肪肝、脂肪性肝炎（NASH）、脂肪性肝纤维化和脂肪性肝硬化四个从轻到重的病理阶段。     

强肝胶囊治疗非酒精性脂肪性肝纤维化的疗效

非酒精性脂肪性肝病(NAFLD)是遗传-环境-代谢应激相关性肝病,肝纤维化是NAFLD发展中的关键阶段,是向肝硬化发展的重要病理过程.肝纤维化发病机制尚未完全明了,目前也缺乏有效安全的抗肝纤维化的治疗方案.本研究应用强肝胶囊治疗非酒精性脂肪性肝纤维化患者半年,观察其在抗肝纤维化方面的疗效,并探讨其机制.     

老年非酒精性脂肪性肝病患者甲状腺激素水平及其与肝纤维化的关系

目的探讨老年非酒精性脂肪性肝病患者甲状腺素水平及其与肝纤维化的关系。方法选取57例2010年5月至2011年11月该院治疗的老年非酒精性脂肪性肝病患者和43例正常老年人为对象进行研究,比较各组患者的甲状腺激素水平和肝纤维化的指标情况。结果两组患者甲状腺激素水平和肝纤维化指标比较有显著性差异(P<0.05)。结论对老年非酒精性脂肪性肝病患者的甲状腺激素水平和肝纤维化程度进行检测,能够评估患者的预后,建议在非酒精性脂肪性肝病老年患者中广泛使用。     

活血化痰颗粒治疗非酒精性脂肪性肝炎25例

非酒精性脂肪性肝病（NAFLD）是一种无过量饮酒史的以肝实质细胞脂肪变性和脂肪贮积为特征的临床病理综合征,疾病谱随病程的进展而表现不一,包括单纯性脂肪肝、脂肪性肝炎（NASH）、脂肪性肝纤维化和肝硬化。     

Cerebral hemodynamics in the non-alcoholic fatty liver

Introduction and objectivesThe association between non-alcoholic fatty liver disease and cerebral hemodynamics arises from cardiovascular damage mechanisms such as endothelial dysfunction, arterial wall increased stiffness, high thickness of the intimate index of the internal carotid artery, left ventricular hypertrophy, left diastolic dysfunction, calcification coronary arteries and increased epicardial fat. The multidirectional relationship between systemic inflammation and lipid metabolism constitutes a common and simultaneous mechanism that causes vascular damage. This study aims to provide insight into the relationship between non-alcoholic fatty liver disease and the function of systemic circulation and cerebral circulation using Doppler ultrasound.Patients and methodsIs an observational, cross-sectional, prospective, comparative study conducted at Medica Sur Hospital. Thirty-five patients were selected consecutively. The patients consulted neurological service for various symptoms without severity criteria, such as vertigo, primary headache and balance disturbances.ResultsThere is a difference in the variables mean of the right MCA PI (p = 0.023), left MCA PI” (p = 0.004), and left VA PI (p = 0.036) between the control and NAFLD groups. The correlation analysis between these variables and the CAP showed a positive correlation of the three variables with the CAP, "right MCA PI" (r = 0.384), left MCA PI "(r = 0.509) and" left VA PI " (r = 0.551).ConclusionsThis study demonstrates a subclinical process of the middle cerebral artery in subjects with NAFLD, which suggests it may be involved in the disease development and points the need to make decisions for this liver manifestation prevention and treatment.     

Fatty liver index vs waist circumference for predicting non-alcoholic fatty liver disease

AIM: To determine the discriminatory performance of fatty liver index(FLI) for non-alcoholic fatty liver disease(NAFLD).METHODS: The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from body mass index, waist circumference(WC), triglyceride, and gamma glutamyl transferase data. Logistic regression analysis was conducted to determine the association between FLI and NAFLD. The discriminatory performance of FLI in the diagnosis of NAFLD was evaluated by receiver operating characteristic analysis. Area under the curves(AUCs) and related confidence intervals were estimated. Optimal cutoff points of FLI in the diagnosis of NAFLD were determined based on the maximum values of Youden's index.RESULTS: The mean age of men and women in the study population were 44.8 ± 16.8 and 43.78 ± 15.43, respectively(P = 0.0216). The prevalence of NAFLD was 40.1% in men and 44.2% in women(P 0.0017). FLI was strongly associated with NAFLD, so that even a one unit increase in FLI increased the chance of developing NAFLD by 5.8%(OR = 1.058, 95%CI: 1.054-1.063, P 0.0001). Although FLI showed good performance in the diagnosis of NAFLD(AUC = 0.8656(95%CI: 0.8548-0.8764), there was no significant difference with regards to WC(AUC = 0.8533, 95%CI: 0.8419-0.8646). The performance of FLI was not significantly different between men(AUC = 0.8648, 95%CI: 0.8505-0.8791) and women(AUC = 0.8682, 95%CI: 0.8513-0.8851). The highest performance with regards to age was related to the 18-39 age group(AUC = 0.8930, 95%CI: 0.8766-0.9093). The optimal cutoff points of FLI were 46.9 in men(sensitivity = 0.8242, specificity = 0.7687, Youden's index = 0.5929) and 53.8 in women(sensitivity = 0.8233, specificity = 0.7655, Youden's index = 0.5888).CONCLUSION: Although FLI had acceptable discriminatory power in the diagnosis of NAFLD, WC was a simpler and more accessible index with a similar performance.     

A new index for non-invasive assessment of liver fibrosis

AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of...     

不同医院无创性肝纤维化指标预测慢性乙型肝炎患者肝纤维化效能差异分析*

目的 探讨应用谷草转氨酶/血小板比值（APRI）、基于4因子的纤维化指数（FIB-4）和瞬时弹性成像技术评判不同医院慢性HBV感染者肝纤维化的效能差异。方法 在2所大学附属医院收治的慢性HBV携带者或慢性乙型肝炎（CHB）行肝穿刺,并获得APRI、FIB-4和肝脏硬度检测（LSM）值,采用ROC曲线分析指标的诊断效能。结果 两组分别纳入327例（A组）和250例（B组）患者,两组患者肝组织病理学检查肝纤维化分期和LSM值存在极显著差异（P值均<0.001）,而APRI和FIB-4值无显著性统计学差异（P=0.547和0.578）;就区分S0-1和≥S2期肝纤维化而言,A组APRI分别为0.14和0.18,B组分别为0.15和0.24,A组FIB-4分别为0.98和1.26,B组分别为0.93和1.50,而A组LSM分别为5.2 kPa和6.8 kPa,B组分别为7.2 kPa和9.0 kPa（P<0.001）;A组和B组APRI诊断的截断点分别为0.105和0.145,FIB-4分别为0.675和0.775,而LSM分别为4.650和6.345,其诊断两家医院患者显著性肝纤维化的灵敏度在85%左右,而特异性在24%~46%之间。结论 可能由于一些不可控制的因素存在,导致临床数据的获得在不同医院间不可比,因此也需要经组织病理学检查,以确定APRI、FIB-4和LSM 诊断显著性肝纤维化的截断点,达到最佳诊断效果。     

脂肪肝指数在非酒精性脂肪性肝病诊断中的应用价值

目的:通过评估脂肪肝指数(FLI),探讨其对非酒精性脂肪性肝病(NAFLD)的筛查和诊断价值。方法:选取年龄大于40岁的上海嘉定地区常住居民共2 519人,通过问卷调查、体格检查及相关人体测量学和生化学指标检测,综合评估人群代谢状态并计算个体FLI。通过高分辨率超声诊断NAFLD。利用受试者工作特征(ROC)曲线评估FLI对于经超声诊断的NAFLD的预测价值。结果:最终共有2 139名受试者纳入统计分析。FLI作为诊断NAFLD的ROC曲线下面积为0.84,95%可信区间为0.82～0.86。当FLI≥30时,其诊断NAFLD的敏感性和特异性最好,灵敏度和特异度分别达到80.6%和73.8%。结论:FLI对于NAFLD的诊断具有较高的参考价值,适用于大样本流行病学研究及指导NAFLD的早期干预和治疗。     

138例药物性肝损伤患者影响预后的因素分析

目的探讨影响药物性肝损伤(DILI)预后的因素。方法 2008年7月至2014年7月在我院住院期间发生DILI患者69例,采用Logistic回归分析影响预后的各个因素。结果本组患者发病年龄主要在50~59岁,女性患者多于男性,肝细胞型占78.3%;各年龄段患者临床类型无显著性差异(P0.05);76.1%DILI患者预后良好,未愈者占23.9%;中药引发的DILI占43.5%,且预后较其他种类药引起者差;患者在住院期间恢复还是未愈与患者性别、年龄、用药至发病时间或是否合并慢性疾病无显著性相关(P0.05),而与临床类型、是否有过敏史、发病时是否出现免疫特性临床表现有显著性相关(P0.05);初始发病时血清总胆红素、总胆汁酸和碱性磷酸酶水平是预测预后的较好指标(P0.05)。结论 DILI患者预后主要取决于用药种类和个体体质差异,初始发病时肝功能指标对预后有一定的预测意义。     

生长抑素通过抑制内质网应激反应减轻肝纤维化小鼠肝损伤研究

目的 观察生长抑素(SST)对肝纤维化(LF)小鼠肝组织内质网应激(ERS)反应的影响。方法 将40只野生型小鼠随机分为对照组、模型组、小剂量SST干预组和大剂量SST干预组,给予小鼠腹腔内注射25% CCl₄ 橄榄油混合制剂制备肝纤维化模型,分别给予大、小剂量的SST进行干预。取肝组织行天狼猩红和免疫组化染色,对肝组织行Ishak评分,采用Western blot法检测肝组织Bcl-2、Bax、Casp-9、BiP和CHOP蛋白表达变化。结果 模型组肝组织炎症活动度评分为(12.2±2.7),显著高于对照组[(1.8±0.8),P＜0.01],肝纤维化程度评分为(5.4±0.5),显著高于对照组[(0.1±0.3),P＜0.01];血清AST 和ALT水平分别为(194.7±35.2)U/L和(121.8±26.6)U/L],均显著高于对照组[分别为(53.8±21.7)U/L和(35.3±12.9)U/L,P＜0.01];大、小剂量SST干预组小鼠肝脏炎症活动度评分分别为(7.7±2.1)和(6.9±1.97),肝纤维化程度评分分别为(4.3±1.0)和(3.9±0.9),较模型组显著改善(P＜0.05);模型组肝组织Bax、Casp-9、BiP和CHOP蛋白相对表达量显著强于对照组([P＜0.01),而SST干预组Bax、Casp-9、BiP和CHOP蛋白相对表达量均显著弱于模型组(F=26.36,F=14.81,F=25.11和F=30.31,P＜0.05)。结论 SST能够改善CCl₄诱导的肝纤维化小鼠肝组织炎症活动和纤维化程度,其机制可能与其抑制了肝组织ERS反应有关。     

脂肪肝危险因素与脂肪肝严重程度的相关因素分析

非酒精性脂肪性肝病是指除外酒精和其他明确损伤因素所致的,以弥漫性肝细胞大泡性脂肪变为主要特征的临床病理综合征.随着肥胖和糖尿病患病率的增加,脂肪肝已成为我国常见的慢性肝病之一,它通常与肥胖,胰岛素抵抗和内脏脂肪的堆积相关[1].此外,非酒精性脂肪性肝病还被认为是以内脏型肥胖、糖尿病、血脂异常和高血压为特征的代谢综合征的临床表现之一[2].内脏脂肪堆积是代谢综合征一个非常重要的危险因素[3].本研究旨在探讨成人内脏脂肪量及其他人体测量指标与脂肪肝及其严重程度的关系,分析脂肪肝的危险因素及影响其严重程度的相关因素,为脂肪肝的防治提供参考.     

Fatty liver index and hepatic steatosis index for prediction of non‐alcoholic fatty liver disease in type 1 diabetes

Background and Aim

Little is known about the diagnostic value of hepatic steatosis index (HSI) and fatty liver index (FLI), as well as their link to metabolic syndrome in type 1 diabetes mellitus. We have screened the effectiveness of FLI and HSI in an observational pilot study of 40 patients with type 1 diabetes.

Methods

FLI and HSI were calculated for 201 patients with type 1 diabetes. Forty patients with FLI/HSI values corresponding to different risk of liver steatosis were invited for liver magnetic resonance study. In‐phase/opposed‐phase technique of magnetic resonance was used. Accuracy of indices was assessed from the area under the receiver operating characteristic curve.

Results

Twelve (30.0%) patients had liver steatosis. For FLI, sensitivity was 90%; specificity, 74%; positive likelihood ratio, 3.46; negative likelihood ratio, 0.14; positive predictive value, 0.64; and negative predictive value, 0.93. For HSI, sensitivity was 86%; specificity, 66%; positive likelihood ratio, 1.95; negative likelihood ratio, 0.21; positive predictive value, 0.50; and negative predictive value, 0.92. Area under the receiver operating characteristic curve for FLI was 0.86 (95% confidence interval [0.72; 0.99]); for HSI 0.75 [0.58; 0.91]. Liver fat correlated with liver enzymes, waist circumference, triglycerides, and C‐reactive protein. FLI correlated with C‐reactive protein, liver enzymes, and blood pressure. HSI correlated with waist circumference and C‐reactive protein. FLI ≥ 60 and HSI ≥ 36 were significantly associated with metabolic syndrome and nephropathy.

Conclusions

The tested indices, especially FLI, can serve as surrogate markers for liver fat content and metabolic syndrome in type 1 diabetes.     

Sexual dysfunctions and their treatment in liver diseases

Sexual dysfunction (SD) is a prevalent but very commonly ignored aspect in the treatment of liver diseases and cirrhosis. The etiology of SD is multifactorial and therefore treatment strategies are complex, especially in females. Phosphodiesterase inhibitors are useful and effective in erectile dysfunction in males but in females, no single drug is available for SD, therefore multimodal treatment is required depending upon the cause. The foremost and fundamental requirement in both genders is to be stress-free and have adequate control of liver diseases. Improved quality of life is helpful in improving SD and vice versa is also true. Therefore, patients suffering from liver diseases should come forward and ask for treatment for SD, and physicians should actively enquire about SD while history taking and evaluating these patients. SD results in deterioration of quality of life, and both are modifiable and treatable aspects of liver diseases, which are never addressed actively, due to social taboos and fears of SD treatment in the presence of liver diseases. The diagnosis of SD does not require costly investigations, as the diagnosis can be established based on validated questionnaires available for both genders, therefore detailed targeted history taking using questionnaires is essential. Data are emerging in this area but is still at an early stage. More studies should be dedicated to SD in liver diseases.