Analysis of Tacrolimus Concentration in Bile: A Patient-Specific Approach to the Early Detection of Acute Rejection After Liver Transplantation

Introduction: Tacrolimus (TAC) stands out as one of the most widely utilized immu-nosuppressive drugs in the prevention of rejection following solid organ transplantation. In case of liver transplantation (LTx), the biochemical pathway for drug metabolism and excretion is an attribute of the transplanted organ, the primary focus of immunological and functional moni-toring. Consequently, the different reduced hepatic functions in every patient may lead to di-minished TAC catabolism and excretion, resulting in a reduced biliary TAC concentration (TACbile) and a consequent elevated blood TAC concentration (TACblood). Our study aims to create a personalized parameter for early the hepatic rejection after LTx by analyzing the hepatic excretion rate of TAC through the evaluation of TACbile and TACblood. Methods: This is a prospective single center observational cohort study. The protocol was registered in Clinicaltri-al.gov (code NCT03882164). Results: The endpoints analyzed in the protocol will be the assess-ment of the predictive ability of TACbile as a marker of early liver rejection and the assessment of a relationship between the reduction in Tacrolimus biliary excretion and Early Allograft Dys-function (EAD). Conclusions: The development of a personalized rejection predictive system could significantly improve the clinical outcome after LTx.