Donor Age Predicts Calcineurin Inhibitor Induced Neurotoxicity After Liver Transplantation

Abstract

Background. Calcineurin inhibitor-induced neurotoxicity (CIIN) is a common and debilitating side effect after liver transplantation (LT). Risk factors and impact on patient outcomes are not well defined. Our aim was to assess the incidence, risk factors, and clinical outcomes of CIIN. Methods. We retrospectively analyzed 175 LTs performed at our center between January 2010 and September 2016. Donor and recipient demographics as well as clinical variables pre-LT, intra-LT, and post-LT were assessed. All patients were on once-daily prolonged-release tacrolimus. Results. CIIN was described in 37 (21.4%) recipients. In univariate analysis, history of hepatic encephalopathy (P = 0.033), immunosuppressant treatment protocol (P = 0.041), donor age (P = 0.002), and pre-LT sodium serum levels (P = 0.004) were associated with CIIN. Patients undergoing LT for hepatocellular carcinoma had lower rates of CIIN (P = 0.040). In multivariate analysis, hepatic encephalopathy (odds ratio [OR], 2.728; 95% confidence interval [CI], 1.098-6.779; P = 0.031), pre-LT serum sodium levels (OR, 1.118 per mEq/L increase, 95% CI, 1.021-1.224; P = 0.016), and donor age (OR, 1.032 per y increase; 95% CI, 1.004-1.062; P = 0.027) were independent risk factors for developing CIIN. In the CIIN group, patients had longer intensive care unit (P = 0.024) and hospital (P = 0.008) stays and more changes in immunosuppressive treatment (54.1% vs 20.4%; P < 0.001). Conclusions. Neurotoxicity remains frequent in patients on once-daily prolonged-release tacrolimus. Antecedents of hepatic encephalopathy, pre-LT sodium serum levels, and donor age are independent risk factors for developing CIIN after LT. CIIN is associated with longer hospital stays and changes in immunosuppressive treatment.

Neurotoxicity after liver transplantation: does donor age matter?

“…Differently to previous publications that found an association between post-LT hyponatremia and CNI neurotoxicity (3), the authors could not show significant differences in post-LT sodium levels between both groups (8). On the other hand, higher pre-LT sodium serum levels (OR 1.118, 95% CI: 1.021-1.224, P=0.016) were an independent predictor of CNI neurotoxicity (8).…”

“…In addition, Yamauchi et al described that a polymorphism in the ABCB1 gene may be a risk factor for tacrolimus induced neurotoxicity in related living donor LT recipients (7). However, few studies have evaluated donor and technical aspects as potential risk factors for CNI-neurotoxicity in liver transplant recipients (8,9).…”

“…In their recent article, Lue et al found that donor age, higher pre-LT sodium levels and previous history of hepatic encephalopathy are independent predictors of CNI neurotoxicity after LT (8). The authors designed a retrospective single-center study with 175 LTs performed in 162 patients in Spain between January 2010 and September 2016.…”

Hepatic encephalopathy: Novel insights into classification, pathophysiology and therapy

“…However, post-LT immunosuppression induced neurotoxicity, particularly from calcineurin inhibitors, should not be disregarded as a causal factor. 149 In addition, perioperative conditions, including seemingly innocuous hypotensive insults, may be detrimental for a compromised brain. Whether neurological complications observed in LT recipients are residual symptoms from a history of HE (pre-LT) or newly developed perioperatively (HE-influenced) or related to a comorbidity is difficult to define accurately.…”

Laparoscopic left hemihepatectomy in small dogs: an easy and effective new technique

“…Hepatectomy is widely used in medical research and experimental surgery, for studying liver failure (Imai et al 2019;Meyer et al 2019;Shirata et al 2019), regeneration (Schadde et al 2017;Tsai et al 2018), and transplantation (Etheredge et al 2019;Lué et al 2019;Majd et al 2019), and is one of the common hepatic procedures performed on companion animals (Boothe 2015;Zhang et al 2014). Thus, an animal model of hepatectomy is an extremely important research tool for evaluating liver regeneration after various treatments (Bernat Córdoba-Jover 2019;de Miguel et al 2019;Lee et al 2019).…”