Abu-Halima Masood, Meese Eckart, Saleh Mohamad Ali, Keller Andreas, Abdul-Khaliq Hashim, Raedle-Hurst Tanja
Institute of Human Genetics, Saarland University Medical Center, Homburg, Germany.
Department of Pediatric Cardiology, Saarland University Medical Center, Homburg, Germany.
Front Cardiovasc Med. 2021 Jan 8;7:619083. doi: 10.3389/fcvm.2020.619083. eCollection 2020.
The present study aims to identify those microRNAs (miRNAs) in patients with univentricular heart (UVH) disease with and without Fontan palliation that may be associated with advanced liver fibrosis/cirrhosis. SurePrint™ 8 × 60K Human v21 miRNA arrays were used to determine the miRNA abundance profiles in the blood of 48 UVH patients with and without Fontan palliation and 32 matched healthy controls. The abundance levels of selected miRNAs have been validated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). According to microarray analysis, 50 miRNAs were found to be significantly abundant in UVH patients of which miR-29b-3p and miR-29c-3p were significantly related to the model of end-stage liver disease (MELD)-Albumin and albumin-bilirubin (ALBI) score representing advanced liver fibrosis/cirrhosis. Relative expression levels of both miRNAs were significantly higher in patients with a higher collapsibility index representing venous hepatic congestion, a higher MELD-Albumin or ALBI score and incomplete or no Fontan palliation. In the logistic regression analysis, a MELD-Albumin score ≥ 11 or ALBI score > -2.6 were best predicted by total bilirubin (OR 6.630, = 0.016), albumin (OR 0.424, = 0.026), and miR-29c-3p (OR 33.060, = 0.047). After adjustment to the status of Fontan palliation, however, no statistical significance of these parameters was found thus underlining the importance of palliation status on progression of liver fibrosis/ cirrhosis in UVH patients. In UVH patients with and without Fontan palliation, miR-29b-3p and miR-29c-3p seem to be markers of advanced liver fibrosis/cirrhosis and thus may be used in the risk assessment of these patients.
本研究旨在确定单心室心脏病（UVH）患者中，无论是否接受Fontan姑息治疗，那些可能与晚期肝纤维化/肝硬化相关的微小RNA（miRNA）。使用SurePrint™ 8×60K人类v21 miRNA芯片，来测定48例接受或未接受Fontan姑息治疗的UVH患者以及32例匹配的健康对照者血液中的miRNA丰度谱。所选miRNA的丰度水平已通过定量逆转录-聚合酶链反应（RT-qPCR）进行了验证。根据芯片分析，发现50种miRNA在UVH患者中显著丰富，其中miR-29b-3p和miR-29c-3p与代表晚期肝纤维化/肝硬化的终末期肝病模型（MELD）-白蛋白和白蛋白-胆红素（ALBI）评分显著相关。在代表静脉性肝充血的塌陷指数较高、MELD-白蛋白或ALBI评分较高且Fontan姑息治疗不完全或未接受Fontan姑息治疗的患者中，这两种miRNA的相对表达水平显著更高。在逻辑回归分析中，总胆红素（OR 6.630，P = 0.016）、白蛋白（OR 0.424，P = 0.026）和miR-29c-3p（OR 33.060，P = 0.047）对MELD-白蛋白评分≥11或ALBI评分＞-2.6的预测效果最佳。然而，在调整Fontan姑息治疗状态后，未发现这些参数具有统计学意义，从而强调了姑息治疗状态对UVH患者肝纤维化/肝硬化进展的重要性。在接受或未接受Fontan姑息治疗的UVH患者中，miR-29b-3p和miR-29c-3p似乎是晚期肝纤维化/肝硬化的标志物，因此可用于这些患者的风险评估。
