Intra-patient variability in tacrolimus exposure in pediatric liver transplant recipients: Evolution, risk factors, and impact on patient outcomes

Pediatr Transplant. 2019 May;23(3):e13388. doi: 10.1111/petr.13388. Epub 2019 Mar 27.

Abstract

Background: This study aims to investigate the evolution and factors associated with TAC IPV and its impact on patient outcomes in pediatric LT recipients.

Methods: This is a retrospective study including 41 children. The TAC IPV was expressed as the coefficient of variation and was calculated for years 1-5 following LT. The number of missed clinic appointments was used as a surrogate marker for therapy adherence.

Results: We identified a decrease in the TAC IPV during the first 3 years after LT (P < 0.01). Serum albumin in the first year (P = 0.03), hematocrit (P = 0.02) and total bilirubin (P = 0.04) in the third year, and therapy adherence (P < 0.01) in the fifth year were associated with TAC IPV. High TAC IPV was associated with biopsy-proven acute allograft rejection (P = 0.04) and the need for biopsy during the first year (P = 0.02). There was a borderline association between TAC IPV and donor-specific antibodies (P = 0.08) and CMV viremia (P = 0.07). High TAC IPV was a predictor of need for liver biopsy and AR with an odds ratio of 1.04 (95% CI 1.0-1.1; P = 0.03) and 1.04 (95% CI 1.0-1.1; P = 0.05), respectively.

Conclusions: Our results highlight the impact of biological factors on TAC IPV during the early LT follow-up and later also therapy adherence. High TAC IPV may be associated with adverse patient outcomes.

Keywords: liver transplantation; pediatric; tacrolimus.

MeSH terms

  • Bilirubin / analysis
  • Biopsy
  • Child
  • Child, Preschool
  • Female
  • Graft Rejection
  • Graft Survival
  • Hematocrit
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Liver / pathology
  • Liver Transplantation*
  • Longitudinal Studies
  • Male
  • Odds Ratio
  • Patient Compliance
  • Pediatrics
  • Retrospective Studies
  • Risk Factors
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Bilirubin
  • Tacrolimus