Retrospective Study
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World J Gastroenterol. Aug 28, 2014; 20(32): 11363-11369
Published online Aug 28, 2014. doi: 10.3748/wjg.v20.i32.11363
''Minimizing tacrolimus'' strategy and long-term survival after liver transplantation
Jun-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
Jun-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
Author contributions: Zheng SS and Zhou L conceived and designed the experiments; He JJ, Geng L, Shen T, Yang Z, Ye YF contributed reagents, materials and analytical tools; Jia JJ and Lin BY wrote the manuscript; Jia JJ, Lin BY, Kadel Dhruba, Wang L and Yu DD performed the experiments; He JJ, Geng L and Kadel D analyzed the data.
Supported by National S and T Major Program, No. 2012ZX10002004; National Natural Science Foundation of China, No. 81373160 and No. 81302074
Correspondence to: Shu-Sen Zheng, MD, PhD, FACS, 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, 866 Yuhangtang Road, Hangzhou 310003, Zhejiang Province, China. shusenzheng@zju.edu.cn
Telephone: +86-571-87236567 Fax: +86-571-87236884
Received: February 9, 2014
Revised: March 20, 2014
Accepted: April 21, 2014
Published online: August 28, 2014
Abstract

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 χ2 test. Routine monitoring of blood TAC concentration (TC) was performed using the PRO-TracTM 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.

Keywords: Tacrolimus, Liver transplantation, Outcome, Minimizing tacrolimus, Immunosuppressive drug

Core tip: Liver transplantation (LT) is a life-saving technique for patients with end-stage liver disease. Tacrolimus (TAC) is the cornerstone immunosuppressant for prevention of graft rejection in many LT centers. However, frequent TAC-related toxicities are observed and these are a major concern in LT patients. Thus, the ‘‘minimizing tacrolimus’’ strategy after LT is very important, especially in the early phase.