Adequate cumulative exposure to tacrolimus and low tacrolimus variability decrease the incidence of biliary...

Area of Science:

• Hepatobiliary surgery
• Transplant immunology
• Pharmacokinetics

Background:

• Non-early biliary complications (BCs) after liver transplantation (LT) are linked to the patient's immunological status.
• Tacrolimus is the primary immunosuppressant used post-LT.
• The precise impact of tacrolimus bioavailability on BCs remains unclear.

Purpose of the Study:

• To investigate the association between tacrolimus bioavailability and the incidence of non-early BCs after LT.
• To determine if tacrolimus trough concentration (C0), cumulative exposure (CET), and variability influence BC development.
• To assess the impact of tacrolimus exposure and variability on overall patient survival.

Main Methods:

• A cohort of 409 LT recipients was analyzed, excluding those on tacrolimus-free regimens or with early BCs.
• Tacrolimus trough concentration (C0), variability, and cumulative exposure (CET) were assessed.
• Receiver operating characteristic (ROC) curves identified optimal cutoff values for CET and variability. Inverse probability of treatment weighting (IPTW) and logistic regression were used for analysis.

Main Results:

• Of 409 patients, 9.5% developed BCs.
• Low CET within 3 months post-LT and high tacrolimus variability were significantly associated with increased BC risk (p < 0.001).
• Appropriate CET and low variability correlated with improved overall survival (p = 0.009 and 0.029, respectively).

Conclusions:

• Maintaining adequate cumulative exposure to tacrolimus (CET) and low variability in its levels can mitigate the incidence of non-early biliary complications post-liver transplantation.
• Optimizing tacrolimus bioavailability is associated with enhanced patient survival outcomes.