Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis
Hepatic and serum levels of miR-122 after chronic HCV-induced fibrosis
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DOI：
10.1016/j.jhep.2012.10.015
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发表时间：
2013-02-01
影响因子：
25.7
通讯作者：
Odenthal, Margarete
中科院分区：
文献类型：
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作者：
Trebicka, Jonel;Anadol, Evrim;Odenthal, Margarete
目的：慢性丙型肝炎（CHC）患者肝纤维化的进展对决定病毒治疗是重要的。由于用于纤维化分期的肝活检和肝硬度测量存在局限性，因此已提出miR-122的循环水平作为预测肝损伤程度的新生物标志物。我们评估了miR-122作为CHC感染中纤维化进展指标的潜力，并首次对CHC.Methods患者的肝脏和循环miR-122水平进行了全面分析：从HepNet数据库（德国病毒性肝炎能力网络）中选择了记录良好的CHC感染患者。所有患者均进行了血液采样和肝活检，并进行炎症分级和纤维化分期。从84例肝活检和164例CHC患者血清中提取RNA。肝脏和血清样品中的miR-122水平通过分别标准化为RNU 6或加标RNA的实时PCR定量。此外，循环miR-122水平与纤维化分期增加呈负相关，尽管由于纤维化进展期间的两相miR-122模式，负相关性为中度。因此，严重纤维化患者（F3，F4）的循环miR-122水平降低，而在早期阶段，具有明显的纤维化结构（F2）和高炎症活性，miR-122血清水平升高。结论：我们得出结论，在纤维化进展过程中，由于肝细胞的损失和肝脏miR-122水平的降低，较少的miR-122被释放到血流中。尽管循环miR-122的释放可能反映了急性肝损伤，但在慢性肝病和纤维化中，肝细胞的损失和肝细胞miR-122表达的降低使得miR-122在专门用于解释纤维化进展时成为不合适的标志物。(C)2012年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background 82 Aims: The progression of liver fibrosis in patients with chronic hepatitis C (CHC) is important to decide on the treatment of the virus. As liver biopsy and liver stiffness measurement for staging of fibrosis present limitations, circulating levels of miR-122 have been suggested as a novel biomarker to predict the extent of liver injury. We evaluated the potential of miR-122 as an indicator of fibrosis progression in CHC infection and performed, for the first time, a comprehensive analysis of hepatic and circulating miR-122 levels in patients with CHC.Methods: Patients with well-documented CHC infection were selected from the database of HepNet, the German-Competence-Network on Viral Hepatitis. All patients underwent blood sampling and liver biopsy with grading of inflammation and staging of fibrosis. RNA was extracted from 84 liver biopsies and 164 serum samples of CHC patients. miR-122 levels in liver and serum samples were quantified by real-time PCR normalized to RNU6 or spiked-in RNA, respectively.Results: Hepatic levels of miR-122 decreased significantly with the severity of fibrosis (p = 0.001). In addition, circulating miR-122 levels correlated negatively with increasing stages of fibrosis, although the inverse correlation was moderate due to a two-phase miR-122 pattern during fibrosis progression. Thus, circulating miR-122 levels decreased in patients with severe fibrosis (F3, F4), while at early stages with distinct fibrotic structures (F2) and high inflammatory activity, miR-122 serum levels were elevated.Conclusions: We conclude that during progression of fibrosis less miR-122 is released into the blood stream due to the loss of liver cells and the decrease of hepatic miR-122 levels. Although the release of circulating miR-122 possibly mirrors acute liver injury, in chronic liver disease and fibrosis, the loss of liver cells and the decreased hepatocellular miR-122 expression render miR-122 an inappropriate marker, when exclusively used for interpretation of fibrosis progression. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.