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Published on: November 8, 2015
''Minimizing tacrolimus'' strategy and long-term survival after liver transplantation
Jun-Jun Jia1, Bin-Yi Lin1, Jiang-Juan He1
1Jun-Jun Jia, Bin-Yi Lin, Jiang-Juan He, Lei Geng, Dhruba Kadel, Li Wang, Dong-Dong Yu, Tian Shen, Zhe Yang, Yu-Fu Ye, Lin Zhou, Shu-Sen Zheng, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China.
Insights
Minimizing tacrolimus (TAC) in liver transplant (LT) patients with a mean blood concentration of 5-10 ng/mL and standard deviation of 2-4 ng/mL improved long-term survival. This strategy also showed comparable adverse effects across different TAC exposure levels.
Area of Science:
- Transplantation Medicine
- Immunosuppression Therapy
- Clinical Outcomes Research
Background:
- Liver transplantation (LT) requires effective immunosuppression to prevent rejection.
- Tacrolimus (TAC) is a cornerstone immunosuppressant, but its narrow therapeutic index necessitates careful management.
- Optimizing TAC dosing is crucial for balancing efficacy and toxicity to improve patient survival.
Purpose of the Study:
- To evaluate the impact of a "minimizing tacrolimus" strategy on long-term survival post-liver transplantation.
- To determine the optimal range for mean and standard deviation of tacrolimus blood concentrations for improved patient outcomes.
- To assess the relationship between early tacrolimus exposure and adverse events after LT.
Main Methods:
- Retrospective analysis of 235 liver transplant recipients from January 2009 to December 2011.
- Kaplan-Meier curves used to analyze the association between early tacrolimus (TAC) exposure and survival.
- Statistical analysis including χ(2) test and Cox regression to evaluate adverse effects and prognostic factors.
- Tacrolimus whole blood concentrations (TC) monitored using ELISA kits.
Main Results:
- Patients with a mean TC < 5 ng/mL had significantly shorter survival times compared to other groups (P < 0.05).
- Survival time was significantly longer for patients with a TC standard deviation (SD) of 2-4 ng/mL compared to other SD groups (P < 0.05).
- Cox regression identified male sex, benign primary disease, mean TC > 5 ng/mL, and TC SD of 2-4 ng/mL as predictors of better outcomes.
Conclusions:
- An early "minimizing tacrolimus" strategy, targeting a mean TC of 5-10 ng/mL and SD of 2-4 ng/mL, is beneficial for long-term survival after LT.
- This optimized TAC management approach appears to improve patient survival without significantly increasing adverse events.
- Individualized TAC monitoring and dose adjustment are critical for enhancing post-transplant outcomes.
Aim:
To investigate the effect of the ''minimizing tacrolimus'' strategy on long-term survival of patients after liver transplantation (LT).
Methods:
We conducted a retrospective study of 319 patients who received LT between January 2009 and December 2011 at the First Affiliated Hospital of Zhejiang University School of Medicine. Following elimination of ineligible patients, 235 patients were included in the study. The relationship between early tacrolimus (TAC) exposure and survival period was analyzed by Kaplan Meier curves. Adverse effects related to TAC were evaluated by the χ(2) test. Routine monitoring of blood TAC concentration (TC) was performed using the PRO-Trac(TM) II Tacrolimus Elisa Kit (Diasorin, United States).
Results:
Of 235 subjects enrolled in the study, 124 (52.8%) experienced adverse effects due to TAC. When evaluating mean TC, the survival time of patients with a mean TC < 5 ng/mL was significantly shorter than that in the other groups (911.3 ± 131.6 d vs 1381.1 ± 66.1 d, 911.3 ± 131.6 d vs 1327.3 ± 47.8 d, 911.3 ± 131.6 d vs 1343.2 ± 83.1 d, P < 0.05), while the survival times of patients with a mean TC of 5-7, 7-10 and 10-15 ng/mL were comparable. Adverse effects due to TAC in all four groups were not significantly different. When comparing the standard deviation (SD) of TC among the groups, the survival time of patients with a SD of 2-4 was significantly longer than that in the other groups (1388.8 ± 45.4 d vs 1029.6 ± 131.3 d, 1388.8 ± 45.4 d vs 1274.9 ± 57.0 d, P < 0.05), while in patients with a SD < 2 and SD > 4, the survival time was not statistically different. Adverse effects experienced in all three groups were not statistically different. In Cox regression analysis, male patients and those with a primary diagnosis of benign disease, mean TC > 5 ng/mL and TC SD 2-4 had better outcomes.
Conclusion:
The early ''minimizing tacrolimus'' strategy with a mean TC of 5-10 ng/mL and SD of 2-4 was beneficial in terms of long-term survival after LT.
