背景 慢性丙肝患者的肝脏纤维化程度的判定，对于决定是否给予抗病毒治疗非常重要。因为肝活检及肝硬度检测方法在判断纤维化分期存在一定的局限性,有人认为血液循环中miR-122水平是预测肝损伤程度的新的生物标志物。目的 本研究评价了miR-122作为慢性丙肝感染的肝纤维程度预测因子的可能性，并且首次综合分析了慢丙肝患者肝内和循环内miR-122水平。方法 入组患者选自德国优势能力网络病毒性肝炎数据库，已明确诊断为慢性丙型肝炎，所有的患者都进行了炎症分级和纤维化分期判定，收集了这些患者的血样和肝活检组织。从84例肝活检组织和167例血样中提取了RNA。用实时定量PCR法测定肝脏中和血样中miR-122水平，并分别进行了RNU6 和spiked-in 标准化。结果 肝纤维化严重时，肝内miR-122水平明显下降，循环中miR-122水平与纤维化程度呈负相关，但纤维化进程中这种负相关由血清和肝脏内miR-122共同调节。因此，循环内miR-122水平，在严重肝纤维时下降，在纤维化早期和炎症活动期升高。结论 我们推断在肝纤维化进程中，由于肝细胞损失，少量的miR-122释放入血，从而使肝脏miR-122水平减低。尽管循环中miR-122的
释放可能反映了急性肝损伤，但在慢性肝病和肝纤维化过程中，肝细胞的丢失和肝内miR-122表达下降，使得miR-122不能成为单独解释纤维化进程的合适的标志物。
吉林大学第一医院肝胆胰内科 王晓美 摘译
本文首次发表于[Journal of hepatology,19 October 2012]
Hepatic and serum levels of miR-122 after chronic HCV induced fibrosis
Background：The progression of liver fibrosis in patients with chronic hepatitis C (CHC) is important in deciding 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. Aims：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 167 serum samples of CHC patients. miR-122 levels in liver and serum samples were quantified by Real Time PCR normalized by 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 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 in 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 to 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 decreased hepatocellular miR-122 expression render miR-122 an inappropriate marker when exclusively used for interpretation of fibrosis progression.
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