Survival Implications of Opioid Use Before and After Liver Transplantation

Background: Implications of prescription opioid use for outcomes after liver transplant have not been described. Methods: We integrated national transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2014; n=26,925). Opioid fills on the waiting list were normalized to morphine equivalents (ME), and exposure was categorized as: >0 to 2 ME/day (level 1), >2 to 10 ME/day (level 2), >10 to 70 ME/day (level 3), and >70 ME/day (level 4). Associations (adjusted hazard ratio, 95% LCL aHR 95% UCL) of pre-transplant ME level with patient and graft survival over 5-years post-transplant were quantified by multivariable Cox regression including adjustment for recipient, donor, and transplant factors, as well as propensity adjustment for opioid use. Results: Overall, 9.3% of recipients filled opioids on the waiting list. Compared to no use, level 3 (aHR 1.061.281.55) and 4 (aHR 1.161.521.98) opioid use during listing were associated with increased mortality over 5 years posttransplant. These associations were driven by risk after the first transplant anniversary, such that mortality >1 to 5 years increased in a graded manner with higher use on the waitlist (level 2: aHR 1.001.271.62; level 3: aHR 1.081.381.77; level 4: aHR 1.492.012.72). Similar patterns occurred for graft failure. Of recipients with the highest level of opioids on the waiting list, 65% had level 3 or 4 use in the first-year after transplant, including 55% with use at these levels from day 90 to 365 post-transplant. Opioid use in the first-year post-transplant also bore graded associations with subsequent death and graft loss >1 to 5 years post-transplant. Conclusions: Opioid use history may be relevant in assessing and providing care to liver transplant candidates. This article is protected by copyright. All rights reserved.