TNF-α在非酒精性脂肪性肝病中的作用及其机制

肿瘤坏死因子-α(TNF-α)是介导肝损伤的主要细胞因子,除对肝细胞的直接作用外,还可通过促进胰岛素抵抗和游离脂肪酸含量的增高,加强葡萄糖毒性和脂毒性造成的肝损害,从而在非酒精性脂肪性肝病(NAFLD)发病中具有重要作用。     

血甘油三酯、尿酸对非酒精性脂肪性肝病患者血清肿瘤坏死因子α、白介素6及胰岛素抵抗的影响

目的观察血甘油三酯(TG)、尿酸(UA)对非酒精性脂肪性肝病(NAFLD)患者血清肿瘤坏死因子α(TNF-α)、白介素6(IL-6)及胰岛素抵抗(IR)的影响。方法从我院就诊经彩色超声诊断的脂肪肝患者中,依血TG水平分为3组,即血TG正常组(NT)、仅血TG升高组(HT组)、血TG合并UA升高组(HTU组),以血TG正常的非脂肪肝人群做对照组(Control)。测各组血清胰岛素、TNF-α、IL-6、血糖,以胰岛素抵抗指数(HOMA-IR)评价IR。结果与Control相比,NT、HT组TNF-α、IL-6、HOMA-IR均无明显增高(P>0.05);HTU组IL-6及HOMA-IR明显增高[IL-6,HTU:135.19(90.27～164.24)ng/mL vs Control:61.6(53.53～79.69)ng/mL;HOMA-IR,HTU:2.34±0.53 vs Control:1.00±0.81,P<0.01],TNF-α无明显增高(P>0.05);相关分析表明,血TG与HO-MA-IR呈明显正相关(r=0.428,P<0.01)。结论 NAFLD患者是否发生IR及IL-6、TNF-α的变化可能受不同TG水平的影响。     

非酒精性脂肪性肝病患者脂肪组织中瘦素、TNF-α基因的表达及意义

研究瘦素(leptin)、TNF-αmRNA在非酒精性脂肪肝病(NAFLD)患者脂肪组织中的表达及意义。定量检测NAFLD患者腹部皮下脂肪组织leptin mRNA、TNF-αmRNA表达水平及评估它们之间的关系。(1)女性皮下脂肪组织中的Leptin mRNA表达水平均显著高于男性(P<0．05);(2)NAFLD组腹部皮下脂肪组织中TNF-αmR- NA的表达水平显著高于非脂肪肝组(P<0．05);男性NAFLD组腹部皮下脂肪组织中leptin mRNA的表达水平显著高于男性非脂肪肝组(P<0．05);(3)男性腹部皮下脂肪组织中leptin mRNA、TNF-αmRNA的表达水平成正相关(r=0．604,P<0．05)。非酒精性脂肪肝患者皮下脂肪组织中存在leptin mRNA、TNF-αmRNA高表达,说明两者均与NAFLD的发生密切相关,在导致NAFLD的发生机制中可能具有协同作用。     

水飞蓟宾胶囊对非酒精性脂肪性肝病患者血清IL-8、TNF-α的影响

目的探讨水飞蓟宾胶囊的肝脏保护作用及机制。方法将58例非酒精性脂肪性肝病（NAFLD）患者随机分为两组各29例,治疗组口服水飞蓟宾胶囊70mg（2粒）,3次／d;对照组口服葡醛内酯片100mg／d：两组均予控制饮食和适当锻炼,疗程30d。检测治疗前后患者血清ALT、AST、IL-8、TNF-α水平。结果治疗后两组患者血清ALT、AST、IL-8、TNF-α水平均有改善（P〈0．01）,但治疗组明显优于对照组（P〈0．01）。结论水飞蓟宾胶囊用于NAFLD患者可改善其肝功能,可能机制为降低血清IL-8、TNF-α水平。     

老年非酒精性脂肪性肝病患者血清瘦素、肿瘤坏死因子-α水平与胰岛素抵抗和体重指数的相关性

目的探讨老年人非酒精性脂肪性肝病(NAFLD)患者血清瘦素(Leptin)、肿瘤坏死因子(TNF)-α水平的变化及与胰岛素抵抗(IR)、体重指数(BMI)的相关性。方法以肝脏CT表现符合脂肪肝的诊断标准,将其分为轻、中、重度脂肪肝。正常对照组选取同期该院健康对照组80例。应用放射免疫法测定所有受试者血清瘦素、TNF-α水平,并测定空腹血糖(FPG)、胰岛素(FINS)水平,计算IR指数(Homa-IR),BMI及腰臀比(WHR)。结果 (1)NAFLD患者FINS,Homa-IR均显著高于对照组;(2)NAFLD血清Leptin、TNF-α水平均显著高于对照组(P0.01)。结论血清瘦素与TNF-α水平在老年人NAFLD中呈正相关性,与肥胖、高血糖及高脂血症、IR密切相关。     

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)包括单纯性脂肪肝以及由其演变的脂肪性肝炎和肝硬化.代谢综合征(MS)是心血管病的多种代谢危险因素在个体内集中的状态,NAFLD常与MS相伴,其发病与MS的各组分密切相关.很多研究表明,肥胖、胰岛素抵抗、血脂紊乱、糖代谢异常、高血压是NAFLD发病的危险因素,而在NAFLD人群中MS的患病率明显增高.因此NAFLD与MS关系密切,具有共同的发病基础,二者的预后、治疗原则相似.     

非酒精性脂肪性肝病患者血清TNF-α、TGF-β1及hs-CRP的检测及意义

目的:探讨TNF-α、TGF-β1、hs-CRP在非酒精性脂肪性肝病患者中的表达及临床意义.方法:选择武汉市第三医院消化内科单纯性脂肪肝51例,非酒精性脂肪性肝炎48例及健康对照者32例,测定血清hs-CRP水平,采用酶联免疫吸附实验(ELISA)测定血清中TNF-α、TGF-β1水平.结果:TNF-α、TGF-β1及hs-CRP是非酒精性脂肪性肝病的独立危险因素.脂肪性肝炎血清hs-CRP、TNF-α水平显著高于单纯性脂肪肝(3.92±1.41 vs 2.01±0.39,8.13±4.21 vs 3.97±0.94,均P<0.05);而脂肪性肝炎和单纯性脂肪肝两组TGF-β1水平差异无显著性.结论:TNF-α和hs-CRP可作为判断非酒精性脂肪性肝病病程发展的指标.     

非酒精性脂肪性肝病与肝移植

非酒精性脂肪性肝病（NAFLD）患病率日益增高,目前已成为西方国家肝移植的第二大适应证。虽然目前我国肝移植的主要适应证仍是乙型病毒性肝炎以及酒精性肝炎相关终末期肝病,但随着人们生活水平的提高以及代谢综合征的流行,与之相关的NAFLD患者也逐渐增加。同时,随着乙型肝炎疫苗接种的普及以及核苷类似物等药物的应用,可以预见,在...     

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。     

非酒精性脂肪性肝病患者血清中IL-8、IL-18的水平及其临床意义

随着非酒精性脂肪性肝病(NAFLD)发病率的逐年上升及对健康的危害,被认为可能是发展成终末期肝病的一个重要病因,NAFLD是一组在不饮酒人群中发生的常见的脂肪性肝病(不包括病毒性肝炎、自身免疫性肝病、遗传性肝病等原因而引起的脂肪肝).NAFLD包括3种类型:单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)、脂肪性肝硬化.其发病机制比较复杂,至今尚未阐明,由胰岛素抵抗(IR)、脂肪酸代谢紊乱、氧应激反应、细胞因子异常等而引起.NASH是由单纯性脂肪肝到隐源性肝硬化的代谢性脂肪肝疾病链中的关键点,探讨多种生物效应的IL-8、IL-18在NASH发病中的作用,测定血清中IL-8、IL-18的浓度,能反映肝细胞损害程度,对判断患者病情、预后有一定的临床意义.     

肿瘤坏死因子α基因多态性与非酒精性脂肪性肝病胰岛素抵抗的相关性

胰岛素抵抗（IR）目前被认为是非酒精性脂肪性肝病（NAFLD）的主要发病机制。研究表明肿瘤坏死因子（TNF）α及其基因多态性与IR关系密切。我们通过检测NAFLD患者的TNFα基因多态性及其血浆水平，探讨了TNFα与IR之间的相关性。     

Genetic polymorphisms of adiponectin and tumor necrosis factor-alpha and nonalcoholic fatty liver disease in Chinese people

Background and Aim:  Hypoadiponectinemia and high tumor necrosis factor-alpha (TNF-α) levels are associated with the development of nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the genetic polymorphisms of adiponectin and TNF-α in Chinese NAFLD patients and their association with disease severity.
Methods:  Seventy-nine patients with histology-proven NAFLD (61 with simple steatosis and 18 with stage 2–4 fibrosis) and 40 controls were tested for the nucleotide polymorphisms at adiponectin −11 391, −11 377, +45, and +276 and TNF-α promoters −863, −308, and −238.
Results:  There was no significant deviation in the adiponectin and TNF-α gene polymorphisms between NAFLD patients and controls, or between patients with simple steatosis and those with stage 2–4 fibrosis. NAFLD patients with −11377G and +45G at the adiponectin gene were more likely to have hypertriglyceridemia. On multivariate analysis, older age, higher body mass index, and higher fasting glucose were independent factors associated with stage 2–4 fibrosis in NAFLD patients.
Conclusions:  Adiponectin and TNF-α gene polymorphisms were not shown to be associated with NAFLD or significant fibrosis in Chinese people. The adiponectin −11377G and +45G alleles were associated with hypertriglyceridemia in NAFLD patients. Since the current study is not adequately powered to detect smaller differences in allele frequencies, larger-sized studies in different ethnic groups are required.     

非酒精性脂肪性肝病患者血清瘦素、脂联素的变化

目的:探讨非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)患者血清瘦素、脂联素的变化.方法:选取NAFLD患者60例,与健康组60例相对照.ELISA法测定血清瘦素、脂联素水平,并与体质量指数(BMI)、腰臀比(WHR)、甘油三脂(TG)、总胆固醇(Tchol)、高密度脂蛋白胆固醇(HDL-C)、血糖(FBG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、谷氨酰转肽酶(GGT)、稳态模型评估的胰岛素抵抗指数(HOMA-IR)相结合,从而判定瘦素、脂联素在NAFLD中的作用.结果:NAFLD组与正常对照组相比,血清瘦素水平升高(12.37±1.99μg/L vs 5.20±41.03 μg/L,P<0.01),脂联素水平降低(12.69±2.83 mg/Lvs 22.83±4.61 mg/L,P<0.01).Logistic多因素回归分析显示瘦素与WHR、HOMA-IR、FBG呈独立正相关(β=8.175,0.974,0.564,P<0.01).脂联素与HOMA-IR、BMI呈独立负相关(β=-0.495,-0.3 14,P<0.01).结论:NAFLD患者血清瘦素水平升高,脂联素水平降低,这两种细胞因子均与胰岛素抵抗相关.     

Serum homocysteine levels in patients with nonalcoholic fatty liver disease

Background and rational for the study. Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic component of insulin resistance (IR) syndrome, but data on serum homocysteine (HCY) are limited. The aim of the study was the evaluation of serum HCY levels in patients with NAFLD. Material and methods. Thirty-one patients (54 ± 11 years, 8 males) with biopsy-proven NAFLD, 15 with simple nonalcoholic fatty liver (NAFL) and 16 with nonalcoholic steatohepatitis (NASH), and 22 healthy controls (52 ± 9 years, 5 males) matched for gender, age and body mass index (BMI), were recruited. Blood samples for HCY, folate, vitamin B12, insulin and standard biochemical tests were obtained after overnight fasting. Homeostatic model of assessment-insulin resistance (HOMA-IR) was calculated. Results. There was no difference in mean serum HCY levels between controls and NAFLD patients (12.6 ± 4.6 vs. 13.5 ± 2.6 mmol/L, respectively; p = 0.432). Serum folate and vitamin B12 were also similar between the study groups. Mean age, BMI, serum folate and vitamin B12 did not differ between NAFL and NASH patients. However, when compared with NAFL patients, NASH patients had lower mean serum HCY levels (12.3 ± 2.5 vs. 14.7 ± 2.1 mmol/L; p = 0.006). HCY was lower by increasing the grading of fibrosis (p = 0.005), portal inflammation (p = 0.029) and steatosis location (p = 0.021). In logistic regression analysis, HCY independently predicted NASH (p = 0.045) after adjustment for gender, age, BMI, AST, glucose and HOMA-IR. Conclusion. Our data suggest that serum HCY levels are lower in NASH compared with NAFL patients and can independently predict NASH. Serum HCY might represent another non-invasive marker for the assessment of NAFLD.     

Significance of genetic polymorphisms in patients with nonalcoholic fatty liver disease

Because of recent advances in genetic research such as genome-wide association studies, the underlying genetic mechanisms of nonalcoholic fatty liver disease (NAFLD) pathophysiology have been elucidated. Here, we present a review of the current literature on the impact of genetic polymorphisms in patients with NAFLD. These genetic polymorphisms, which regulate lipid metabolism, glucose metabolism, and the renin-angiotensin system, are involved in NAFLD onset, steatosis, inflammation, fibrosis, and hepatocellular carcinoma (HCC). Among these genetic polymorphisms, many studies and meta-analyses have demonstrated that position 148 (rs738409 C/G) of the patatin-like phospholipase domain-containing protein (PNPLA3) is a genetic factor associated with NAFLD pathophysiological features, such as hepatic fat level, hepatic inflammation, fibrosis, and HCC. However, the impact of genetic polymorphisms on NAFLD pathophysiology appears to differ among ethnic groups. Therefore, further studies with larger sample sizes are needed for each ethnic group.     

High interleukin-6 and tumor necrosis factor-alpha serum levels in hepatitis C infection associated or not with mixed cryoglobulinemia

The objective of this study is to evaluate serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a) in a series of patients with hepatitis C virus (HCV)-related mixed cryoglobulinemia (HCV-MC) and to correlate these parameters with the clinical features of the disease. Serum IL-6 and TNF-a were assayed in 61 patients with HCV-MC, in 61 sex- and age-matched patients with HCV chronic hepatitis without cryoglobulinemia (HCV+), and in 61 sex- and age-matched healthy controls. HCV-MC patients showed significantly higher mean IL-6 levels than controls (p=0.005) or HCV+ patients (p = 0.02). Moreover, IL-6 was increased in cryoglobulinemic patients with active vasculitis, even if the statistical significance was not reached (p=0.056). Serum TNF-a levels were significantly higher in HCV-MC than in HCV+ or in controls (p<0.01). The study demonstrates high IL-6 and TNF-a serum levels in HCV-MC patients; moreover, IL-6 levels tended to be higher in HCV-MC patients in presence of active vasculitis.