Serum miRNA signatures in recovery from acute and chronic liver injury and selection for liver transplantation.

We have previously demonstrated a distinct hepatic miRNA signature (downregulation of miRNA-23a, -150, - 200b, -503, -663 and upregulation of miRNA-20a) is associated with successful regeneration in auxiliary liver transplantation (ALT). This study aimed to evaluate whether the serum expression of this regeneration-linked miRNA signature is associated with clinical outcomes in acute and chronic liver disease. These were represented by patients with acetaminophen (APAP) induced acute liver failure (ALF) (n=18) and patients with hepatitis C (HCV) undergoing treatment with direct-acting antivirals (DAA) (n=56) respectively. Patients were grouped depending on their clinical outcome. Global serum miRNA expression was analysed using PCR-arrays and selected miRNA expression using targeted PCR. We demonstrate that specific regeneration-linked miRNAs discriminate outcomes in both clinical scenarios. We further show that miRNA-20a, -23a, -150, -200b, -503 and -663 undergo concordant changes in expression in 3 distinct clinical settings, liver regeneration accompanying successful ALT, clinical recovery after ALF, and clinical recompensation after cure of HCV. This miRNA signature represents a potentially novel biomarker to predict outcome and optimise patient selection for liver transplantation in both acute and chronic liver disease.