武汉云克隆科技股份有限公司

Abstract:

OBJECTIVES:

Nonalcoholic steatohepatitis (NASH) is the most severe form of a hepatic condition known as nonalcoholic fatty liver disease (NAFLD). NASH is histologically characterized by hepatic fat accumulation, inflammation, and ballooning, and eventually coupled with fibrosis that, in turn, may progress to end-stage liver disease even in young individuals. Hence, there is a critical need for specific noninvasive markers to predict hepatic inflammation at an early age. We investigated whether plasma levels of cathepsin D (CatD), a lysosomal protease, correlated with the severity of liver inflammation in pediatric NAFLD.

METHODS:

Liver biopsies from children (n=96) with NAFLD were histologically evaluated according to the criteria of Kleiner (NAFLD activity score) and the Brunt's criteria. At the time of liver biopsy, blood was taken and levels of CatD, alanine aminotransferase (ALT), and cytokeratin-18 (CK-18) were measured in plasma.

RESULTS:

Plasma CatD levels were significantly lower in subjects with liver inflammation compared with steatotic subjects. Furthermore, we found that CatD levels were gradually reduced and corresponded with increasing severity of liver inflammation, steatosis, hepatocellular ballooning, and NAFLD activity score. CatD levels correlated with pediatric NAFLD disease progression better than ALT and CK-18. In particular, CatD showed a high diagnostic accuracy (area under receiver operating characteristic curve (ROC-AUC): 0.94) for the differentiation between steatosis and hepatic inflammation, and reached almost the maximum accuracy (ROC-AUC: 0.998) upon the addition of CK-18.

CONCLUSIONS:

Plasma CatD holds a high diagnostic value to distinguish pediatric patients with hepatic inflammation from children with steatosis.

摘要：

目的：

俗称非酒精性脂肪肝的非酒精性脂肪肝炎（NASH）最严重的一种肝脏疾病。其病理特征依次表现为肝脂肪堆积、炎症、胀气、器官纤维化，最终可能会发展到肝病晚期。甚至一些年轻人也受到疾病的困扰。因此，迫切需要一种特异性无创标志物能够早期预测肝炎。我们发现一种溶酶体蛋白酶——血浆组织蛋白酶D（CatD）与小儿肝炎相关。

方法：

按Kleiner标准(NAFLD评分)和Brunt标准对96例NAFLD患儿的肝活检进行组织病理学评价。肝活检：抽血，检测血浆组织蛋白酶D（CatD）、丙氨酸转氨酶（ALT）和细胞角蛋白-18（CK-18）的水平。

结果：

与正常受试者对比，肝炎患者血浆组织蛋白酶D（CatD）的水平显著降低。此外，我们发现随着肝炎、脂肪变性、肝细胞球囊化和NAFLD活性评分的增加，CatD水平逐渐降低。CatD与小儿NAFLD的相关性优于ALT和CK-18。尤其是CatD对脂肪变性和肝脏炎症的诊断准确率(ROC-AUC)=0.94，如果加上CK-18，几乎可以达到最大准确率（ROC-AUC=0.998）。

结论：

血浆CatD水平对脂肪变性引起的小儿肝炎具有较高的诊断意义。

使用试剂原文信息：Plasma samples were diluted and CatD levels were determined by the CatD enzyme-linked immunosorbent assay according to the manufacturer’s protocol (Uscn Life Science, Wuhan, China).