Kanaan Reine, Yaghi Cesar, Saade Riachy Carole, Schlosser Anders, Hamade Aline, Holmskov Uffe, Medlej-Hashim Myrna, Sørensen Grith Lykke, Jounblat Rania
Department of Cancer and Inflammation Research Institute of Molecular Medicine, University of Southern Denmark Odense Denmark.
Laboratory of Cellular and Molecular Physiopathologies (CAMP), Department of Life and Earth Sciences, Faculty of Sciences Lebanese University Beirut Lebanon.
JGH Open. 2023 Feb 23;7(3):197-203. doi: 10.1002/jgh3.12873. eCollection 2023 Mar.
Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in different countries. Liver fibrosis is considered as the most appropriate predictor of NAFLD-associated outcome. Microfibrillar-associated protein 4 (MFAP4) is a glycoprotein located in the extracellular matrix. Circulatory MFAP4 has been suggested as a noninvasive biomarker for the assessment of hepatitis C virus and alcoholic liver disease associated liver fibrosis. In this study, we aimed to investigate the association between serum MFAP4 and liver fibrosis severity in NAFLD patients.
A case-control study was conducted in which NAFLD patients ( = 25) and healthy participants ( = 12) were recruited. Liver fibrosis/cirrhosis was assessed by transient elastography (TE) and biochemical parameters were collected. Serum MFAP4 was measured by sandwich ELISA based on two monoclonal anti-MFAP4 antibodies and calibrated with a standard of recombinant MFAP4.
Serum MFAP4 levels increased with fibrosis severity and were highly upregulated in patients with cirrhosis (F4 fibrosis stage). In addition, serum MFAP4 levels positively correlated with TE measurement and showed significant association with the severely advanced fibrotic stage in NAFLD patients, in multiple linear regression analysis following adjustment for age, gender, and body mass index.
This study suggests the use of MFAP4 as a potential diagnostic noninvasive biomarker for cirrhosis screening in NAFLD patients.
非酒精性脂肪性肝病(NAFLD)是不同国家慢性肝病的主要病因。肝纤维化被认为是NAFLD相关预后的最合适预测指标。微原纤维相关蛋白4(MFAP4)是一种位于细胞外基质的糖蛋白。循环中的MFAP4已被提议作为评估丙型肝炎病毒和酒精性肝病相关肝纤维化的非侵入性生物标志物。在本研究中,我们旨在探讨NAFLD患者血清MFAP4与肝纤维化严重程度之间的关联。
进行了一项病例对照研究,招募了NAFLD患者(n = 25)和健康参与者(n = 12)。通过瞬时弹性成像(TE)评估肝纤维化/肝硬化,并收集生化参数。基于两种抗MFAP4单克隆抗体,采用夹心ELISA法测定血清MFAP4,并以重组MFAP4标准品进行校准。
血清MFAP4水平随纤维化严重程度增加而升高,在肝硬化(F4纤维化阶段)患者中高度上调。此外,血清MFAP4水平与TE测量值呈正相关,在对年龄、性别和体重指数进行校正后的多元线性回归分析中,显示与NAFLD患者严重进展期纤维化阶段有显著关联。
本研究提示MFAP4可作为NAFLD患者肝硬化筛查的潜在诊断性非侵入性生物标志物。