Department of Internal Medicine I, University of Bonn, Germany.
J Hepatol. 2013 Feb;58(2):234-9. doi: 10.1016/j.jhep.2012.10.015. Epub 2012 Oct 22.
BACKGROUND & 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.
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.
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.
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.
慢性丙型肝炎（CHC）患者肝纤维化的进展对于决定病毒的治疗方法很重要。由于肝活检和肝硬度测量在纤维化分期方面存在局限性，因此循环 miR-122 水平已被提议作为一种预测肝损伤程度的新型生物标志物。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 患者的肝内和循环 miR-122 水平进行了全面分析。
从德国病毒性肝炎网络（HepNet）数据库中选择有明确 CHC 感染病史的患者。所有患者均接受了血液取样和肝活检，以进行炎症分级和纤维化分期。从 84 例 CHC 患者的肝活检和 164 例血清样本中提取 RNA。通过实时 PCR 分别用 RNU6 或掺入的 RNA 对肝和血清样本中的 miR-122 水平进行定量。
肝内 miR-122 水平随纤维化严重程度显著降低（p = 0.001）。此外，循环 miR-122 水平与纤维化分期的增加呈负相关，尽管由于纤维化进展过程中的两相 miR-122 模式，这种负相关程度适中。因此，在严重纤维化（F3、F4）患者中，循环 miR-122 水平降低，而在纤维化结构明显（F2）和炎症活性高的早期阶段，miR-122 血清水平升高。
我们的结论是，在纤维化进展过程中，由于肝细胞的丢失和肝内 miR-122 水平的降低，进入血液的 miR-122 减少。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，肝细胞的丢失和肝细胞中 miR-122 表达的降低使 miR-122 成为一种不合适的标志物，当单独用于解释纤维化进展时。
Zotero 插件