非酒精性脂肪性肝病患者瘦素与肝纤维化的关系

目的:研究非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)患者血清瘦素水平与肝纤维化指标的相关性,来探讨瘦素在NAFLD发展进程中的作用.方法:应用放射免疫法(RIA)测定33例NAFLD患者及30例对照组的瘦素、透明质酸(HA)、层粘蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C),并测定空腹血糖(FBG)、总胆固醇(TC)、三酰甘油(TG)、空腹胰岛素(FINS)、体质量指数检测(BMI)等临床指标.结果:NAFLD患者的瘦素、BMI、空腹胰岛素及胰岛素抵抗指数(HOMA IR)分别为11.07 μg/L±3.40 μg/L、27.33±2.98、14.19 mU/L±2.65 mU/L、3.48±0.65,显著高于对照组(P＜0.05);血清PCⅢ、Ⅳ-C、LN、HA在轻度NAFLD患者分别为68.17 μg/L±19.31 μg/L、39.06 μg/L±13.84 μg/L、62.51 μg/L±21.37 μg/L、44.52 μg/L±14.73 μg/L,与对照组比较无显著性差异(P＞0.05),在中、重度NAFLD患者分别为164.62 μg/L±18.47 μg/L、83.32 μg/L±24.73μg/L、152.22 μg/L±20.74 μg/L、212.51 μg/L±19.62 μg/L,明显高于对照组(P＜0.05),以HA最为显著(P＜0.01);轻度NAFLD患者,其血清瘦素与肝纤维化指标无相关关系(P＞0.05);中、重度NAFLD患者血清瘦素水平与肝纤维化指标有相关关系(P＜0.05).结论:瘦素与NAFLD患者肝纤维化进程密切相关.     

酒精性肝病患者血清瘦素水平与肝纤维化的关系

瘦素(leptin)是由肥胖基因编码的产物。实验研究显示活化的肝星状细胞(HSC)瘦素合成明显增加,提示瘦素可能与肝纤维化有关。现拟探讨酒精性肝病患者血清瘦素水平与肝组织纤维化的关系。 1.资料与方法:(1)研究对象:酒精性肝病(ALD)患者60例,均为男性,诊断依据2001年中华医学会肝病学分会脂肪肝酒精肝学组制定的“酒精性肝病诊断标准”。酒精性脂肪肝14例,     

酒精性肝病患者血清瘦素水平的变化与临床意义

目的　研究瘦素与酒精性肝病 (ALD)肝纤维化发生发展的关系。方法　用ELISA方法检测 6 0例ALD患者血清瘦素水平 ,16位健康人作为对照组 ,同步检测了ALD患者的血清肝纤维化指标HA、LN、PCⅢ及TGFβ1,对血清瘦素与肝纤维化指标、肝组织纤维化分期间的关系进行了分析。结果　ALD患者的血清瘦素水平明显高于对照组 ,在酒精性脂肪肝 (AFL)、酒精性肝炎 (AH)、酒精性肝硬化 (ALC)瘦素水平依次增高 ,差异有显著性。在AH、ALC血清瘦素水平与肝纤维化血清学指标和TGFβ1正相关 ,ALD患者的血清瘦素水平与肝组织纤维化分期密切相关。结论　血清瘦素是ALD患者肝纤维化的始动因子之一。     

瘦素与非酒精性脂肪性肝纤维化研究进展

瘦素是肥胖基因编码的代谢性激素,主要在白色脂肪组织特异表达,结合受体后介导细胞信号转导途径,通过调节肝脏间质细胞功能、调控转化生长因子β(TGF-β)、肿瘤坏死因子α(TNF-α)等细胞因子的分泌以及诱导胶原生成与降解失衡等,参与非酒精性脂肪性肝纤维化的发生发展。     

非酒精性脂肪性肝病患者肝纤维化与舌象特征的关系

目的:探讨非酒精性脂肪性肝病(NAFLD)患者肝纤维化评分(NFS)与舌象特征的关系。方法:从中日友好医院体检中心随机招募确诊为NAFLD的受试者,收集受试者的人口学资料、测量学指标、实验室指标等,按标准化流程采集受试者的舌象照片并进行校正与标注,比较不同舌象特征的受试者间NFS评分的差异。结果:NAFLD患者舌色上以暗红舌为主,苔色上以淡黄苔为主。暗红舌、紫舌、黄苔及舌质瘀点和瘀斑的NAFLD患者的NFS评分显著高于淡红舌、白苔、无瘀点和瘀斑的患者;紫舌患者中NFS>0.676的比例显著高于淡红舌、红舌和暗红舌的患者(P<0.05);舌质瘀点和瘀斑的患者中NFS>0.676的比例亦显著高于舌质无瘀点和瘀斑的患者(P<0.05)。结论:暗红舌、紫舌、黄苔、舌质瘀点和瘀斑对NAFLD患者肝纤维化有重要的提示作用。     

瘦素与肝纤维化

瘦素（leptin）是1994年首次通过定向克隆技术成功克隆的一种代谢性激素,由肥胖（OB）基因编码,人OB基因位于7号染色体的长臂（7q31．3）,由3个外显子和2个内含子构成。瘦素是一种分泌蛋白,由167个氨基酸组成,相对分子质量为16000。瘦素必须与相应受体（ob—R）结合才能发挥作用。目前发现ob-R有a、b、c、d、e和f6种亚型,其中ob-Rb为长型受体,也是功能性受体,ob—Re是可溶性受体,与循环中的瘦素形成复合物,通过调节游离与结合的瘦素比例可改变其生物学活性,其余为短型受体叫。     

瘦素与肝纤维化

Zhang等[1]应用定向克隆法从肥胖与糖耐量异常的动物ob/ob小鼠中首次成功克隆出肥胖基因(obese gene,ob基因)及人类的同源序列,由于该基因编码蛋白的基本作用是使动物体重降低而变瘦,故Halaas等[2]将其命名为瘦素(leptin)。瘦素主要由脂肪细胞表达,具有中枢性抑制摄食作用。近来发现,瘦素可存在于胎盘和胃等脂肪组织以外的组织[3,4],具有广泛的生物学效应。最新的一些临床与实验研究显示,活化的     

非酒精性脂肪性肝病肝纤维化诊治研究进展

非酒精性脂肪肝（NAFLD）是指除外长期大量饮酒和其他损伤肝脏因素所引起的以肝脏脂肪沉积为主要表现的临床综合征,患者肝脏脂肪代谢功能出现明显障碍,使得大量脂肪类物质蓄积于肝细胞,导致肝细胞发生脂肪变性,从单纯性非酒精性脂肪肝（NAFL）发展到非酒精性脂肪性肝炎（NASH）,最终发展为肝纤维化、肝硬化和终末期肝病,甚至肝癌。近年来由于发病率逐渐升高引起人们的重视。     

瘦素与肝纤维化关系及研究方法

瘦素与肝纤维化关系密切.本文结合既往的动物实验以及作者对肝组织原位瘦素的研究, 推测肝脏原位瘦素的出现可能意味着肝纤维化进程启动的一个重要步骤,并对瘦素研究方法进行分析.     

酒精性肝病患者血清瘦素及其受体基因Gln223Arg多态性变化

目的 观察酒精性肝病患者血清瘦素（Lep）水平及其受体（LEPR）基因Gln223Arg多态性变化,并探讨其意义.方法 选择酒精性肝病患者106例,其中酒精性脂肪性肝炎45例（AH组）,酒精性肝硬化61例（AC组）,同期健康体检者65例作为对照组.采用ELISA法检测血清Lep,葡萄糖氧化酶—过氧化物酶法检测空腹血糖（FPG）,化学发光免疫分析法检测空腹血清胰岛素（FINS）,PCR-RFLP法检测LEPR基因Gln223Arg多态性,并计算HOMA-IR.结果 AH组血清Lep、HOMA-IR分别为（8.95±1.81） ng/mL、2.44±0.25,AC组分别为（10.57±2.00） ng/mL、3.21 ±0.17,对照组分别为（4.44±0.81） ng/mL、1.77 ±0.18;AH组、AC组与对照组比较,P均＜0.05.AH组、AC组血清Lep与HOMA-IR均呈正相关（r=0.45、0.38,P均＜0.01）.AH组AA、A/G、GG的例数分别为3、11、31例,AC组分别为0、25、36例,对照组分别为1、12、52例;AC组与对照组比较,P＜0.05.结论 酒精性肝病患者血清Lep、HOMA-IR水平升高,AC组患者LEPR基因Gln223 Arg杂合基因频率高于健康人群,可能通过胰岛素—瘦素轴促进胰岛素抵抗,影响体内脂肪代谢,参与酒精性肝病的发病机制.     

Changes in laminin content in livers of patients with alcoholic liver disease

Abstract: An increase in serum laminin levels has been reported in patients with liver disease; however, the mechanisms for this increase have not yet been clarified. In the present study, the laminin content of liver biopsy specimens obtained from patients with alcoholic liver disease and nonalcoholic liver disease was determined with a one-step sandwich enzymeimmunoassay system, using monoclonal antibodies for human placental laminin. Hepatic laminin content was significantly higher in patients with liver disease than in normal controls. In alcoholic liver disease, the content in patients with mild fibrosis was lower than in patients with advanced types of alcoholic liver disease. In non-alcoholic liver disease, the hepatic laminin content tended to increase in parallel with the progression of fibrosis. The laminin content in alcoholic liver disease was significantly higher than in the corresponding type of non-alcoholic liver disease. Hepatic total collagen content increased in parallel with the progression of fibrosis in both alcoholic liver disease and non-alcoholic liver disease. The ratio of laminin to total collagen content was highest in alcoholic liver disease showing mild fibrosis and decreased in parallel with the progression of fibrosis. In contrast, the ratio was low in all types of nonalcoholic liver disease. The ratio in patients with alcoholic liver disease was significantly higher than in those with the corresponding non-alcoholic liver disease. Hepatic laminin content increased in parallel with the increase in hepatic type IV collagen in alcoholic liver disease, and the correlation was statistically significant. However, a similar correlation was not found in non-alcoholic liver disease. These results indicate that the response of laminin synthesis to alcoholic liver disease is strong in mild fibrosis and reached a plateau at a relatively early stage of fibrosis. The stimulation for laminin synthesis in non-alcoholic liver disease is different from that in alcoholic liver disease.     

Hepatic collagen synthesis in patients with alcoholic and nonalcoholic liver disease

To examine the synthesis of hepatic collagen in patients with alcoholic and nonalcoholic liver disease, liver biopsy specimens were incubated in vitro with¹⁴C-proline, and the radioactivity of the newly synthesized protein-bound¹⁴C-hydroxyproline was measured. Mean hepatic collagen synthesis was 0.82±0.19 pmole of¹⁴C-hydroxyproline/g liver/2 h in control subjects without histological liver fibrosis. Hepatic collagen synthesis was increased in patients with alcoholic and nonalcoholic liver diseases, especially in those with alcoholic fibrosis, alcoholic cirrhosis and chronic active hepatitis. The raised collagen synthesis in alcoholic liver disease rapidly decreased after withdrawal of alcohol. When alcoholic liver disease were compared with nonalcoholic liver disease, there was no significant difference in hepatic collagen synthesis. This work was supported in part by a grant-in-aid for EncourageMent of Young Scientists (No.57770489) from the Ministry of Education, Science and Culture of Japan.     

Clinical usage of serum ferritin to assess liver fibrosis in patients with non‐alcoholic fatty liver disease: Proceed with caution

Serum ferritin was recently reported to have low diagnostic accuracy for the detection of advanced fibrosis in patients with non‐alcoholic fatty liver disease (NAFLD). To corroborate these findings, we investigated the diagnostic accuracy of serum ferritin levels for detecting liver fibrosis in NAFLD patients utilizing a large Japanese cohort database. A total 1201 biopsy‐proven NAFLD patients, seen between 2001 and 2013, were enrolled into the Japan Study Group of NAFLD. Analysis was performed on data from this cohort comparing between serum ferritin levels and hepatic histology. Serum ferritin increased with increasing histological grade of steatosis, lobular inflammation and ballooning. Multivariate analyses revealed that sex differences, steatotic grade and fibrotic stage were independently associated with serum ferritin levels (P < 0.0001, <0.0001, 0.0248, respectively). However, statistical analyses performed using serum ferritin levels demonstrated that the area under the receiver–operator curve for detecting fibrosis was not adequate for rigorous prediction. Several factors including sex differences, steatosis and fibrosis were found to correlate with serum ferritin levels. Therefore, serum ferritin may have low diagnostic accuracy for specifically detecting liver fibrosis in NAFLD patients due to the involvement of multiple hepatocellular processes.     

慢性病毒性肝炎患者血清中瘦素与肝纤维化指标的关系

研究血清瘦素水平与慢性病毒性肝炎和肝纤维化之间的关系。用放射免疫法检测 4 5例慢性乙型肝炎(CHB)患者血清中的瘦素和肝纤维化指标的水平。发现CHB患者血清瘦素水平 (7 6 3± 2 19)ng/ml显著高于正常对照组 (3 82± 1 0 9)ng/ml,其瘦素 /BMI值也显著高于正常对照组 ,CHB患者的血清瘦素水平与肝纤维化指标层粘蛋白 (LN)、透明质酸 (HA)、Ⅲ型前胶原 (PCⅢ )和Ⅳ胶原 (ⅣC)的水平呈正相关。瘦素与慢性病毒性肝炎肝纤维化的形成密切相关     

常用血清学指标与慢性乙型肝炎肝纤维化程度相关性研究

目的：研究常用血清学指标与慢性乙型肝炎肝纤维化程度的关系。方法：对177例慢性乙型肝炎患者进行血清肝脏生化和肝纤维化指标检测，包括丙氨酸氨基转移酶（AIT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）、总胆红素（TBil）、白蛋白（Alb）、球蛋白（Glo）、透明质酸（HA）、层粘连蛋白（LN）、Ⅲ型前胶原蛋白（PcⅢ）、Ⅳ型胶原蛋白（CⅣ）。所有病例均行肝穿刺活检，并进行肝组织纤维化分期（S）。结果：部分血清学指标与肝组织纤维化程度相关，以Alb、Glo、HA、PCⅢ、CⅣ相关性最好，相关系数分别为-0．299、0．282、0．595、0．387、0．480。伴随肝纤维化程度的增加，血清白蛋白呈下降趋势，而血清球蛋白、HA、PCⅢ、CⅣ呈上升趋势。结论：部分血清学指标能反映肝组织纤维化程度，对于难以开展肝穿刺活检的单位可以帮助肝纤维化诊断。