Impact of Hispanic ethnicity on tacrolimus dosing in liver transplant patients

Purpose: To determine if Hispanic patients require higher doses of tacrolimus to maintain therapeutic concentrations compared with Caucasian patients after liver transplantation, as dose-requirement differences between other ethnic groups have been recognized.

Methods: A retrospective single-center review of Hispanic and Caucasian liver recipients transplanted between 1/1/07-12/31/10 was conducted. Included patients had stable liver function and stable tacrolimus dosing (3 consecutive levels on the same dose) at 3 months post-transplant. Exclusion: age less than 18, previous transplant, total bilirubin above 3mg/dL, or survival less than 6 months. The primary endpoint was tacrolimus dose (mg/day) at 3 months post-transplant; secondary endpoints included tacrolimus dose (mg/kg/day), tacrolimus dose/concentration ratio and 6 month rejection rates.

Results: 374 charts were reviewed; 133 were included with 85 Caucasian and 48 Hispanic subjects. There were no differences in baseline characteristics between groups for age, gender, hepatitis C, or BMI. The mean tacrolimus mg/day and mg/kg/day dose at 3 months was 7.7 ± 3.4 mg/day (0.092 mg/kg/day) for Caucasian patients and 9.0 ± 3.8 mg/day (0.107 mg/kg/day) for Hispanic patients (mg/day p=0.04, mg/kg/day p=0.103). The average tacrolimus trough at 3 months was 7.1 ± 1.9 ng/mL and 8.7 ± 2.8 ng/mL in the Caucasian and Hispanic groups, respectively (p=0.0002). There was no statistical difference in the concentration/dose ratio [(ng/ml)/(mg/kg/day)] between the groups, 97.7 ± 59.1 in the Hispanic group and 110.7 ± 93.2 in the Caucasian group (p=0.3273). Rejection in the first 6 months was rare, occurring in 8 and 5 patients in the Caucasian and Hispanic groups, respectively (p=0.85).

Conclusions: At 3 months post-transplant, Hispanic patients had higher tacrolimus dose requirements but achieved higher trough concentrations than Caucasian patients. No differences in rejection were seen. Future studies are needed to determine if hypermetabolism of tacrolimus in Hispanic patients exists as it does with other ethnic populations.