Lower tacrolimus trough levels in the late period after living donor liver transplantation contribute to improvements in long-term clinical outcomes

Hepatobiliary Pancreat Dis Int. 2018 Jun;17(3):204-209. doi: 10.1016/j.hbpd.2018.05.001. Epub 2018 May 17.

Abstract

Background: Previous studies have emphasized the need to reduce tacrolimus (TAC) trough levels in the early post-liver transplantation (LT) period. However, whether late-period TAC trough levels influence the long-term outcomes of liver recipients is not clear.

Methods: We enrolled 155 adult liver recipients survived more than 3 years after living donor liver transplantation because of non-malignant liver diseases. The maintenance immunosuppressive regimens were TAC monotherapy and combined therapy with mycophenolate mofetil. Patients were divided into three groups according to their late-period TAC trough levels: < 3 ng/mL group, 3-5 ng/mL group, and >5 ng/mL group. The complications and adverse effects of TAC were analyzed.

Results: Each group showed similar rejection, graft loss and mortality. Patients achieved the < 5 ng/mL state in less than 4 years had fewer new-onset diabetes, hyperlipidemia, de novo malignancies, and hepatitis B virus recurrence; the complications of renal dysfunction and hypertension rates were the same among these 3 groups.

Conclusions: Collectively, our findings indicated that lower TAC trough levels in the late period of liver transplantation are safe, improve the long-term outcomes.

Keywords: Complications; Immunosuppression; Liver transplantation.

MeSH terms

  • Adult
  • Aged
  • Calcineurin Inhibitors / administration & dosage
  • Calcineurin Inhibitors / adverse effects
  • Calcineurin Inhibitors / blood*
  • Calcineurin Inhibitors / pharmacokinetics
  • Drug Monitoring
  • Drug Therapy, Combination
  • Female
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood*
  • Immunosuppressive Agents / pharmacokinetics
  • Kaplan-Meier Estimate
  • Liver Transplantation / adverse effects
  • Liver Transplantation / methods*
  • Liver Transplantation / mortality
  • Living Donors*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Retrospective Studies
  • Risk Factors
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects
  • Tacrolimus / blood*
  • Tacrolimus / pharmacokinetics
  • Treatment Outcome
  • Young Adult

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • Mycophenolic Acid
  • Tacrolimus