title: ''Minimizing tacrolimus'' strategy and long-term survival after liver transplantation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Jia
authors.affiliation: 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.
authors.forename: Bin-Yi
authors.initials: BY
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Jiang-Juan
authors.initials: JJ
authors.lastname: He
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Geng
authors.affiliation: 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.
authors.forename: Dhruba
authors.initials: D
authors.lastname: Kadel
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Tian
authors.initials: T
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Yu-Fu
authors.initials: YF
authors.lastname: Ye
authors.affiliation: 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.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Zheng
mesh_terms: D000328:Adult; D065095:Calcineurin Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D002681:China; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Immunosuppressive drug; Liver transplantation; Minimizing tacrolimus; Outcome; Tacrolimus