Abstract
Background and Aims: News strategies for the accurate assessment of the state of immunosuppression (IS) in liver transplant recipients are needed to prevent rejection and minimize drug-related side effects. miRNAs can potentially be used as diagnostic or prognostic biomarkers in transplant patients. This study evaluated the capacity of a plasmatic miRNA panel (miR-155-5p, miR-122-5p, miR-181a-5p, and miR148-3p) as an early non-invasive prognostic and diagnostic biomarker for T cell-mediated acute rejection (TCMAR) and subclinical rejection (SCR) in adult liver recipients.Methods: A total of 145 liver recipients were included. All patients received a calcineurin inhibitor with or without mycophenolate mofetil and methylprednisolone. Plasmatic miRNA expression was assessed by qPCR before and at different time-points after liver transplantation.Results: Seventeen patients experienced TCMAR, and eight were diagnosed with SCR during the protocol biopsy at the 3rd month post-transplantation. Pre-transplantation, miR-155-5p expression was significantly higher in TCMAR patients and in SCR patients than in non-rejectors, and miR-181a-5p expression was also significantly higher in SCR patients than in non-rejectors. Post-transplantation, before transaminase-level modification, significantly increased miR-181a-5p, miR-155-5p, and miR-122-5p expression was observed in TCMAR and SCR patients. Binary logistic regression analyses showed, post-transplantation, that TCMAR risk was better predicted by individual expression of miR-181a-5p (LOGIT = −6.35 + 3.87*miR-181a-5p), and SCR risk was better predicted by the combination of miR-181a-5p and miR-155-5p expression (LOGIT = −5.18 + 2.27*miR-181a-5p+1.74*miR-155-5p).Conclusions: Pre-transplantation plasmatic miR-155-5p expression may be useful for stratifying low-immunologic-risk patients, and post-transplantation miR-181a-5p and miR-155-5p may be candidates for inclusion in early, non-invasive prognostic biomarker panels to prevent TCMAR or SCR and better identify patient candidates for IS minimization. Large prospective randomized multicenter trials are needed to refine the cut-off values and algorithms and validate the clinical usefulness of these biomarkers.
Highlights
Despite great advances in immunosuppressive (IS) therapy, T cell-mediated rejection (TCMAR), which is the main form of rejection in liver transplantation (LT), has an incidence estimated ∼21–27% [1, 2]
Twelve patients remained on the LT waiting list at the end of the inclusion period, 6 died before undergoing LT, and 15 patients did not met the minimum follow-up period for several reasons: 5 died before month 3; 1 transplant could not be performed because of a technical impossibility found during surgery; 4 patients withdrew consent; and 5 had no complications but a shorter than 3-month follow up at the time of analysis
We found that the plasmatic expression of miR-181a-5p, miR-155-5p, and miR-122-5p were statistically significant higher in TCMAR and in subclinical rejection (SCR) patients compared with non-rejectors and could diagnose and prognostic TCMAR and SCR with high accuracy
Summary
Despite great advances in immunosuppressive (IS) therapy, T cell-mediated rejection (TCMAR), which is the main form of rejection in liver transplantation (LT), has an incidence estimated ∼21–27% [1, 2]. The availability of non-invasive biomarkers of an alloimmune response may provide physicians useful information to better identify patients at high risk of rejection and those who are good candidates for IS minimization post-transplantation and to achieve more personalized IS therapy. Monitoring these biomarkers may decrease the requirement for the use of biopsies [3]. This study evaluated the capacity of a plasmatic miRNA panel (miR-155-5p, miR-122-5p, miR-181a-5p, and miR148-3p) as an early non-invasive prognostic and diagnostic biomarker for T cell-mediated acute rejection (TCMAR) and subclinical rejection (SCR) in adult liver recipients
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