Patients and Sample collection
All the liver transplantation recipients included in this study met the following criteria: age > 18 years, postoperative survival time ≥ 3 months, normal liver function within 1 month following surgery, and patients having received treatment with tacrolimus in combination with steroids and mycophenolate mofelil after transplantation. The corresponding donors met the following criteria: hepatitis or other infectious disease free, normal liver and kidney function, and no treatment with any drug known to interact with tacrolimus within the two previous weeks.
Tacrolimus was administered orally at a dose of 0.05 mg/kg/d twice daily from the first day following transplantation. Routine therapeutic drug monitoring (TDM) for tacrolimus was initiated 48 h after the administration of its first dose. The initial tacrolimus concentration (C0) in whole blood was determined through an enzyme amplification immunoassay using the EMIT 2000 tacrolimus assay kit (Siemens Healthcare Diagnostics, DE, USA) on the day of blood collection. The tacrolimus C0/D ratio was calculated by dividing the tacrolimus concentration by the corresponding weight-adjusted dose. Liver samples of the included donors were collected during liver trimming at the time of transplantation, cut into small pieces, and immediately stored in liquid nitrogen.