The Medication Level Variability Index (MLVI) Predicts Poor Liver Transplant Outcomes: A Prospective Multi-Site Study

Publication Type
Journal Article
Year of Publication
2017
Authors
Shemesh, E; Bucuvalas, J C; Anand, R; Mazariegos, G V; Alonso, E M; Venick, R S; Reyes-Mugica, M; Annunziato, R A; Shneider, B L
Secondary
Am J Transplant
Volume
17
Start Page
2668
Pagination
2668-2678
Date Published
10/2017
Keywords
biomarker; calcineurin inhibitor; Clinical research/practice; clinical trial; compliance/adherence; immunosuppressant; liver allograft function/dysfunction; liver transplantation/hepatology; pediatrics; Tacrolimus
Abstract

Nonadherence to immunosuppressant medications is a leading cause of poor long-term outcomes in transplant recipients. The Medication Level Variability Index (MLVI) provides a vehicle for transplant outcome risk-stratification through continuous assessment of adherence. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi-site study evaluated whether MLVI predicts late acute rejection (LAR). Four hundred pediatric (1-17-year-old) liver transplant recipients were enrolled and followed for 2 years. The a-priori hypothesis was that a higher MLVI predicts LAR. Predefined secondary analyses evaluated other outcomes such as liver enzyme levels, and sensitivity analyses compared adolescents to pre-adolescents. In the primary analysis sample of 379 participants, a higher prerejection MLVI predicted LAR (mean prerejection MLVI with LAR: 2.4 [3.6 standard deviation] versus without LAR, 1.6 [1.1]; p = 0.026). Fifty-three percent of the adolescents with MLVI>2 in year 1 had LAR by the end of year 2, as compared with 6% of those with year 1 MLVI‚ȧ2. A higher MLVI was significantly associated with all secondary outcomes. MLVI, a marker of medication adherence that uses clinically derived information, predicts LAR in pediatric liver transplant recipients.