*Purpose: Tacrolimus (FK506) oral bioavailability in pediatric liver transplant recipients (LTR) is poor. Enteral FK506 is primarily absorbed in the small intestine and subject to intestinal and hepatic first pass metabolism. Roux-en-Y (RNY) choledochojejunostomy biliary reconstruction may alter FK506 absorption by bypassing small intestine segments. This study aims to compare FK506 bioavailability in pediatric LTR with a RNY biliary reconstruction compared to those with native small intestine anatomy.

*Methods: All pediatric (age < 18 years) LTRs performed at our institution between 2012 and 2020 were retrospectively reviewed. LTRs were excluded for multi-organ or re-transplant, non-FK506-based immunosuppression, or patient death within 1-month of transplant. Immunosuppression includes FK506 and corticosteroid taper +/- mycophenolate. FK506 bioavailability was assessed using Dose-Normalized Trough Concentration (DNTC), measured as the trough concentration (ng/mL) divided by total daily dose (mg/kg/day), at months 1, 6, 12, and 24. Biliary reconstruction was categorized as RNY or native small intestine anatomy [duct-to-duct or choledochoduodenostomy (CDD)]. Categorical variables were compared using Chi-squared test and continuous variables using Student’s t-test. Association with DNTC was assessed using multivariable linear regression.

*Results: 88 pediatric LTRs met inclusion criteria. 47 (53%) underwent RNY choledochojejunostomy and 41 (47%) maintained native small intestine anatomy (duct-to-duct = 24, CDD = 17). RNY recipients were significantly younger at transplant (3.53 [4.43] vs. 7.17 [6.41] years, p = 0.002), had biliary atresia (77% vs. 12%, p < 0.001) and received a living donor graft (40% vs. 10%, p = 0.004). Time to therapeutic FK506 levels was not significantly different between groups. FK506 DNTC was significantly greater in the RNY group at 1-, 6- and 24-months (Figure 1). Age at transplant had a significant negative association with FK506 DNTC at all time points. RNY status was not significantly associated with FK506 DNTC after adjusting for age.

*Conclusions: Pediatric LTR with RNY choledochojejunostomy had greater FK506 bioavailability in our cohort, though primarily driven by younger age. Therefore, bypassing a segment of small intestine for RNY choledochojejunostomy does not significantly alter enteric FK506 absorption and metabolism. Investigation into age-related factors, such as developmental pharmacokinetics, is warranted to further evaluate this relationship.

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