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Room: E-Poster Hall

P-18.25 High intrapatient variability of tacrolimus exposure after liver transplantation as new marker of poor outcomes

CRISTINA DOPAZO, Spain

CONSULTANT SURGEON
DEPARTMENT OF HPB SURGERY AND TRANSPLANTS
HOSPITAL UNIVERSITARIO VALL D´HEBRON, UNIVERSIDAD AUTONOMA DE BARCELONA

Abstract

High intrapatient variability of tacrolimus exposure after liver transplantation as new marker of poor outcomes

Cristina Dopazo1, Sonia Garcia2, Bruno Montoro2, Inmaculada Concepcion Gomez-Gavara1, Mireia Caralt1, Lluis Castells3, Isabel Campos-Varela3, Ernest Hidalgo1, Ramon Charco1, Itxarone Bilbao1.

1Department Of HBP Surgery And Transplants, Hospital Universitario Vall D´Hebron, Barcelona, Spain; 2Department of Pharmacology, Hospital Universitario Vall D´Hebron, Barcelona, Spain; 3Unit of Hepatology, Department of Internal Medicine, Hospital Universitario Vall D´Hebron, Barcelona, Spain

Introduction: Tacrolimus (TAC) is a critical dose drug with a considerable intrapatient variability (IPV) in its pharmacokinetics. The priority is to preserve graft function and patient survival, and to minimize pharmacological adverse events.
Aim: The aim of our study was to evaluate the impact of mean concentration and IPV of trough levels of TAC on outcomes during the first year post-LT.
Methods: A single-center cohort study which analyze retrospectively those adult patients transplanted among 2015-2019 and one year of follow-up. We excluded from the analysis those patients who died within the first month. Because we hypothesized that a high IPV during the first 6 months could result in frequent over-inmunosuppression, the outcome of interest was a composite end point named “event”, which consisted of patient lost and glomerular filtration rate <60mL/min/1.73m2 at one year post-LT. The IPV of TAC concentrations was estimated by calculating the coefficient of variation (CV) of whole blood trough concentrations during the first 6 months post-LT.
Results: One hundred fifty-eight patients were included in the present study. Thirty patients (27%) reached the composite end point “event”. One-year renal dysfunction was 21% and the rate of patient lost was 8%. The median CV during the first month in the group who reached the composite end-point was 47% (r:21%-98%)  vs 48%(r:12%-135%) in the group who did not reach the composite end point (p=ns). This CV value decreased between 1-3month post-LT [26% (r:2%-105%) vs 26% (r:3%-82%)] (p=ns) finding significant differences between 3-6 months [32% (r:1%-174%) vs 17% (r:2%-65%)] (p=0.002). The multivariate analyses showed pre-LT cardiological disease (OR 16, p 0,08) and CV>30% at 6 months post-LT(OR 7; p 0,001) were the main risk factors for the composite end-point “event”.
Conclusion: Optimize TAC levels after LT should be the “goal” and IPV can be used as an easy monitoring tool  to help identify high-risk patients of poor outcomes.

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