title: Medication level variability index predicts rejection, possibly due to nonadherence, in adult liver transplant recipients.
abstract: Nonadherence to immunosuppressants may play a role in late rejection in liver transplant recipients. In children, emerging data suggest that adherence can be measured through the computation of the standard deviation (SD) of consecutive blood levels of tacrolimus, which results in a number that reflects the degree of variability between individual measures: the medication level variability index (MLVI). A higher MLVI value means erratic immunosuppression, likely due to less adherence. Data on this method are limited for adults. We obtained data from the medical charts of 150 randomly selected adult recipients. The MLVI was significantly higher for patients who had biopsy-confirmed rejection (mean MLVI = 3.8, SD = 3.2) versus the rest of the cohort (mean MLVI = 2.3, SD = 1.5, P = 0.003), and it was significantly higher for patients who suffered rejection versus patients whose biopsy sample was not read as rejection (mean MLVI = 2.6, SD = 1.6, P = 0.008). The MLVI was associated with rejection and predicted its occurrence. A threshold MLVI of 2.0 resulted in 77% sensitivity and 60% specificity in predicting rejection; a threshold of 1.8 resulted in a sensitivity of 92% and a specificity of 48%. The area under the curve in a receiver operating characteristic curve analysis was 0.71 (95% CI = 0.61-0.81). In conclusion, the MLVI is associated with and can predict rejection, possibly related to nonadherence, in adult liver transplant recipients.
authors.affiliation: Department of Pediatrics and Kravis Children's Hospital, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Psychology, Fordham University, Bronx, NY.
authors.forename: Supelana
authors.initials: S
authors.lastname: Christina
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Annunziato
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Schiano
authors.forename: Ravinder
authors.initials: R
authors.lastname: Anand
authors.forename: Swapna
authors.initials: S
authors.lastname: Vaidya
authors.forename: Kelley
authors.initials: K
authors.lastname: Chuang
authors.forename: Yelena
authors.initials: Y
authors.lastname: Zack
authors.forename: Sander
authors.initials: S
authors.lastname: Florman
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Shneider
authors.forename: Eyal
authors.initials: E
authors.lastname: Shemesh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009518:New York / Q000453:epidemiology; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D013997:Time Factors; D066027:Transplant Recipients; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D007166:Immunosuppressive Agents