Elsevier

Transplantation Proceedings

Volume 46, Issue 9, November 2014, Pages 3117-3120
Transplantation Proceedings

24th Congress of the Spanish Liver Transplantation Society
Complication
Differences in the Incidence and Clinical Evolution of Early Neurotoxicity After Liver Transplantation Based on Tacrolimus Formulation Used in the Immunosuppressive Induction Protocol

https://doi.org/10.1016/j.transproceed.2014.10.006Get rights and content

Abstract

Introduction

Posttransplant early calcineurin inhibitor (CNI)-induced neurotoxicity (ECIIN) was related to high CNI levels, among other factors. Minimizing exposure could modify its incidence or clinical evolution.

Objective

To compare the incidence, predisposing factors, and clinical evolution of ECIIN after immunosuppressive induction with low-dose tacrolimus-MR (Advagraf) or conventional dose tacrolimus (Prograf).

Patients and Methods

We matched 71 patients treated with an immunosuppression induction schedule with basiliximab and low doses of Advagraf (cases group) 1:1 by recipient age and indication for liver transplantation (OLT) with patients treated with a conventional tacrolimus regimen (control group). Baseline characteristics, liver and kidney function, operative technical characteristics, kidney function, and C0 tacrolimus levels at several time points after liver OLT were analyzed.

Results

There were 31 cases of ECIIN (21%), 14 in the cases group (20%) and 17 in the control group (24%; P < .001). The incidence of ECIIN was higher in alcoholic liver disease (odds ratio [OR], 8.2; 95% CI, 2.3–28.6; P < .001) and past history of encephalopathy (OR, 2.6; 95% CI, 1.16–5.9; P < .02). Among cases, the incidence of ECIIN was higher when encephalopathy signs were present at time of transplantation (36% vs 12%; P < .001). Control of ECIIN required a switch to cyclosporine therapy in all those in the cases group, whereas this was only needed for 9 cases in the control group (47%; P < .001).

Conclusion

In this study, although the incidence rate of neurotoxicity induced by Advagraf was lower than the induced by Prograf, it did not respond to routine treatment and required a significantly higher rate of switch to cyclosporine for its control.

Section snippets

Patients and Methods

We designed a matched, case-control study recording baseline characteristics, pretransplant liver and kidney function parameters, operative technical characteristics, kidney function after OLT, and tacrolimus levels during the first month after OLT. Seventy-one consecutive liver patients recipients (cases group) treated from February 2011 to December 2012 with an immunosuppressive induction regimen using basiliximab (20 mg in days 1 and 4 posttransplantation), a standard tapering steroids

Results

We analyzed 142 patients (120 men and 22 women) who underwent liver transplantation at a mean age of 56.2 ± 8.3 years, with a Model for End-stage Liver Disease score of 13.1 ± 5.4. Alcoholic cirrhosis was present in 86 cases (61%) and viral cirrhosis in 30 (21%). Fifty-six patients (38%) had a past history of encephalopathy, with 34 presenting (23%) with clinical signs at transplantation. There were no differences in the baseline, technical characteristics, or donor age between cases and

Discussion

CNI-induced neurotoxicity is among the more debilitating adverse events after OLT, with a prevalence rate of 6% to 47% of recipients treated with CNI-based immunosuppression [7]. Clinical manifestation range from mild tremor to an early, severe syndrome defined by confusion, agitation, altered level of consciousness, seizure, psychosis, focal symptoms, coma, or leukoencephalopathy, and in absence of other neurologic lesion (ie, ECIIN) [8]. ECIIN is considered as the most frequent adverse event

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    However, this surrogate marker imperfectly reflects TAC immunosuppressive activity or toxicity. Indeed, in patients undergoing LT, TACblood was not able to predict the occurrence of acute cellular rejection2 or TAC-related adverse effects,3,4 especially during the early postoperative days (PODs) because the liver graft is progressively recovering its metabolic function.5 This is particularly true considering TAC neurotoxic effects, which occur in approximately 20%4 of the patients after LT. In fact, this can be neither predicted nor treated except by temporary TAC suspension and subsequent spontaneous regression.

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