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酒精性肝病患者中,肝脏、脂肪组织及血清中的骨桥蛋白水平与肝纤维化相关

作者: 赵旭 发布日期: 2012-07-12 阅读次数:
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 目的:骨桥蛋白(OPN)在慢性肝脏疾病的进程中起重要作用。我们旨在测量酗酒者的肝脏、脂肪组织和血清中的OPN水平,并将之与肝脏炎性改变、肝纤维化的组织学严重程度做对照比较。方法:在以下四组中分别评估骨桥蛋白水平:1、回顾组109名酗酒者血清中OPN水平;2、前瞻组95名酗酒者血清中OPN水平;3、回顾组34名患者肝脏中OPN水平;4、附加组(第二基因组)38名酗酒者肝脏及脂肪组织中OPN水平。结果:肝脏存在炎性改变的患者, 血清中的OPN水平轻度增高,并随纤维化的严重程度加重而逐渐增高。肝脏中的OPN表达水平与肝脏炎性改变、纤维化、转化生长因子表达水平、中性粒细胞聚集以及血清中的OPN水平有关。有趣的是,脂肪组织中OPN的表达水平同样与肝脏纤维化有关,这种关联甚至于在戒酒7天以后仍然存在。在一个综合了碱性磷酸酶、白蛋白、血红蛋白、ONPFibroMeter水平的模型中,血清中OPN水平在评价显著性肝纤维化中被认为是一个单独的危险因素。 OPN在对回顾组和前瞻组评估显著性肝纤维化的ROC曲线下面积分别是0.890.88OPN,透明质酸(0.88),细胞角蛋白-180.83)以及FibroMeter0.9),在对回顾组的评估方面具有相同的显著程度。最后,在86个慢性丙肝患者中,血清中OPN水平也与肝脏纤维化及显著性肝纤维化有关,提示其水平升高可能是对慢性肝损伤的常规反应。结论:在出现肝纤维化的饮酒患者中,OPN在肝脏、脂肪组织及血清中含量升高。另外,OPN是评价肝纤维化的一项新的生物标志物。因此OPN在慢性肝脏疾病的发病机制中可能起到重要作用。

 

吉林大学第一医院肝胆胰内科  赵旭 摘译

本文首次发表于[PLoS One. 2012;7(4):e35612. ]

 

The Osteopontin Level in Liver, Adipose Tissue and Serum Is Correlated with Fibrosis in Patients with Alcoholic Liver Disease

Abstract

BACKGROUND AND AIMS: Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.

METHODS: OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers.

RESULTS: Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase , albumin, hemoglobin, OPN and FibroMeter® levels , OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC:0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.

CONCLUSIONS: OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.

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作者: 赵旭 发布日期: 2012-07-12 阅读次数: