MicroRNA 29c-3p indicates advanced liver fibrosis/cirrhosis in univentricular heart patients with and without Fontan palliation

Abstract

Background: In patients with chronic liver disease that usually results in liver fibrosis, microRNAs (miRNAs) have been shown to be of diagnostic and prognostic value. The present study aims to identify those miRNAs in patients with univentricular heart (UVH) disease with and without Fontan palliation that may be associated with advanced liver fibrosis/cirrhosis. Methods:A large panel of human miRNA arrays were used to determine miRNA abundance profiles in the blood of 48 UVH patients with and without Fontan palliation and 32 age and gender-matched healthy controls. The most abundantly expressed miRNAs identified by microarray analysis were correlated to prognostic scores of advanced liver fibrosis/cirrhosis and selected miRNAs validated by RT-qPCR.Results: 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 correlated to the model of end-stage liver disease (MELD)-Albumin and albumin-bilirubin (ALBI) score. According to ROC analysis, a MELD-Albumin score ≥ 11 was best predicted by total bilirubin (AUC 0.985, P=0.005), collapsibility index (AUC 0.952, P=0.009) and miR-29c-3p (AUC 0.941, P=0.011) and the most significant predictors of an ALBI score >−2.6 were collapsibility index (AUC 0.998, P<0.001) and albumin (AUC 0.981, P=0.006).In the multivariate analysis, miR-29c-3p turned out to be an independent predictor of advanced liver fibrosis/cirrhosis as defined by a MELD-Albumin score ≥ 11 (P=0.004) and ALBI score > −2.6 (P=0.009), respectively. Conclusion:In UVH patients with and without Fontan palliation, miR-29c-3p seems to be an independent predictor of advanced liver fibrosis/cirrhosis and thus may be used in the risk assessment of these patients.