Non-adherence and graft failure in adult liver transplant recipients.
BACKGROUND
Non-adherence to medical therapy after liver transplantation is confounded by different methods of measurement.


OBJECTIVE
(1) To compare the performance of three different methods of measuring non-adherence: (a) biochemical (standard deviation [SD] tacrolimus levels), (b) clinician report, (c) self-report. (2) To identify pre-transplant predictors of post-transplant non-adherence. (3) To evaluate whether SD tacrolimus is an accurate predictor of graft outcomes.


METHODS
In this retrospective cohort study, charts of adult recipients of a liver transplant 2003-2009 (sample A, n = 444) were reviewed to determine pre-transplant predictors of non-adherence and clinician report of non-adherence. SD tacrolimus levels were measured between 6 and 18 months post-transplant. A subset of sample A (n = 122) completed a survey on non-adherence. The three methods were compared using linear and logistic regression. Multivariable analysis was used to investigate pre-transplant predictors of non-adherence. In sample B (transplant recipients 1995-2003, n = 544) Cox regression was used to determine the relationship between SD immunosuppressant level and graft failure.


RESULTS
Non-adherence was found in 22-62 % of subjects, with the highest rates indicated by self-report. Clinician report of non-adherence was associated with both self-report and SD tacrolimus. On multivariable analysis, unemployment at time of listing and chart evidence of pre-transplant non-adherence were significant predictors of higher SD of tacrolimus. History of substance abuse and pre-transplant chart evidence of non-adherence were also significant independent predictors of post-transplant chart evidence of non-adherence. Drug variability in the immediate post-transplant setting was independently associated with graft failure over time (hazard ratio 1.005 per unit increase in standard deviation, p = 0.04).


CONCLUSIONS
Non-adherence among liver transplant recipients is a common problem associated with increased risk of graft failure. SD tacrolimus can be used to measure non-adherent behavior and perhaps target patients for behavioral interventions.
University of Michigan Medical School, M4101 Medical Sciences I, SPC 5624, 1301 Catherine Road, Ann Arbor, MI 48109, USA. srlieber@med.umich.edu
Sarah R
SR
Lieber
Michael L
ML
Volk
D015331:Cohort Studies; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012944:Social Support; D011795:Surveys and Questionnaires; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D016903:Drug Monitoring
D007166:Immunosuppressive Agents; D016559:Tacrolimus