Neurotoxicity after liver transplantation: does donor age matter?

Abstract

Early calcineurin inhibitors (CNIs)-induced neurotoxicity is a serious and frequent complication after liver transplantation (LT). It takes place in 6-47% of LT recipients treated with CNI, and it is associated with significant mortality, morbidity, and prolonged hospital stay (1-3). Controversy continues over which patients have a greater risk of developing CNI neurotoxicity after LT (4). The incidence of early CNI neurotoxicity is higher in LT recipients receiving tacrolimus compared with patients receiving cyclosporine (5). Major central nervous system manifestations are diverse, and they are commonly classified as minor (tremor, headache, insomnia, paresthesia), and major (encephalopathy, akinetic mutism, seizures, speech disorders, polyneuropathy, psychosis) (3). Different ways of treating early CNI neurotoxicity have been described, such as a decrease in the dosage of CNI using other immunosuppressant drugs (mycophenolate mofetil or everolimus), switching from tacrolimus to cyclosporine or vice versa, and even CNI withdrawal in the most severe cases (2).Several retrospective studies have investigated the risk factors and possible mechanism of CNI neurotoxicity. Most studies have focused on recipients' risk factors: age, MELD score, ALT, bilirubin, creatinine, glycemia, hypocholesterolemia, hyponatremia, hypomagnesemia, h y p e r t e n s i o n , a l c o h o l c o n s u m p t i o n a n d h e p a t i c encephalopathy (2,3,6) have been shown as potential risk factors for CNI neurotoxicity. 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).