Hepatic encephalopathy and post-transplant hyponatremia predict early calcineurin inhibitor-induced neurotoxicity after liver transplantation

Early calcineurin inhibitor-induced neurotoxicity (ECIIN) is considered when neurological symptoms occur within 4 weeks after liver transplantation (LT). Risk factors and clinical outcome of ECIIN remain largely unknown. We sought to estimate the incidence, risk factors, and outcome of ECIIN after LT. We retrospectively evaluated 158 patients that underwent LT in a 2-year period and received immunosuppression with calcineurin inhibitors (CNI) and prednisone. ECIIN was considered when moderate/severe neurological events (after excluding other etiologies) occurred within 4 weeks after LT and improved after modification of CNI. Demographic and clinical variables were analyzed as risk factors. Twenty-eight (18%) patients developed ECIIN and the remaining 130 patients were analyzed as controls. History of pre-LT hepatic encephalopathy (OR 3.16, 95% CI 1.29-7.75, P = 0.012), post-LT hyponatremia (OR 3.34, 95% CI 1.38-9.85, P = 0.028), and surgical time >7 h (OR 2.62, 95% CI 1.07-6.41, P = 0.035) were independent factors for ECIIN. Acute graft rejection and infections were more frequent in the ECIIN group. In addition, length of stay was longer in ECIIN patients. In conclusion, pre-LT hepatic encephalopathy, surgical time >7 h, and post-LT hyponatremia are risk factors for ECIIN. Clinical complications and a longer hospital stay are associated with ECIIN development.