Plasma microRNAs and chemokines as biomarkers for rejection in liver transplantation with score verification and tissue correlation

The use of biomarkers in liver transplantation (LT) may be useful for the noninvasive assessment of T-cell-mediated rejection (TCMR). This study aimed to: (1) determine if changes in circulating microRNAs (miRNAs) in rejector patients reflect those at the tissue level; (2) assess a biomarker score (including miRNAs 155-5p, 181a-5p, and CXCL-10) in an independent cohort and (3) evaluate the score's utility in detecting other LT-related complications. A prospective cohort of 151 LT recipients was followed during the first year after surgery. Patients with abnormal liver function tests (LFTs) underwent liver biopsy (LB) to rule out TCMR. Plasma samples were collected at predefined time points to analyse miRNAs and chemokines and their ability to predict and diagnose TCMR. To correlate plasma biomarkers with their tissue expression, 27 liver tissue samples (9 with normal LFTs and 18 with TCMR) were selected. Forty patients were diagnosed with TCMR. Circulating miRNAs (155-5p and 122-5p) reflected tissue-level changes in TCMR (p < 0.001, 3.3-fold increase for miR-155 and 2.3 for miR-122). Additionally assessed plasma miRNA 885-5p and chemokines CXCL-9 and CXCL-11, were also significantly elevated in TCMR but did not improve the performance of our previously biomarker score for TCMR (AUROC 0.94 for prediction, 0.99 for diagnosis). In conclusion, we confirmed in an independent cohort the performance of the score based on miR-155-5p, miR-181a-5p, and CXCL10. The correlation between circulating miRNAs and liver tissue expression underscores their value for predicting and diagnosing TCMR.