P111 Tacrolimus reintroduction after tacrolimus-associated neurotoxicity in liver transplant patients

<h3></h3> Tacrolimus is widely used for immunosuppression in liver transplantation; its use is however associated with neurotoxicity. Tacrolimus-associated neurotoxicity is heterogeneous in presentation and may manifest as headache, tremor and psychological symptoms with more severe cases developing disturbances in cortical function and seizures potentially as part of the posterior reversible encephalopathy syndrome (PRES). Management may involve drug cessation but data on drug reintroduction are lacking. We describe the frequency and pattern of the diagnosis of major tacrolimus neurotoxicity in a cohort of patients undergoing liver transplantation; we also describe the proportion who restarted tacrolimus and the subsequent rate of further complications. We reviewed a prospective database of adult patients undergoing first liver or liver-kidney transplants at our centre from 2015–01-01 until 2023–05-08 with ≥1 year follow-up (or death). Records were inspected for additional data. 779 patients were included. 286 (37%) were female, median (IQR) age was 61 (IQR 53 to 67) years. Most frequent aetiologies were alcohol 232 (30%), metabolic dysfunction associated steatotic liver disease (25%), primary sclerosing cholangitis 88 (11%) and primary biliary cholangitis in 54 (7%); 109 (14%) had hepatocellular carcinoma. 244 (31%) had pre-transplant chronic and 33 (4%) acute hepatic encephalopathy. Overall, 72 (9%) stopped tacrolimus after a diagnosis of neurotoxicity at 16 (10–35) days after transplantation; peak pre-dose levels were 9.8 (7.8–13.6) µg/l. Problems provoking cessation included: delirium 48 (67%); psychosis 9 (11%); reduced consciousness 8 (10%), seizures 8 (10%), hallucinations 6 (8%) and visual disturbances 4 (6%); 46 (64%) underwent neuroimaging and in 7 (10%) this was reported as compatible with PRES. Age, sex and disease aetiology did not correlate with tacrolimus cessation; prior chronic hepatic encephalopathy was associated (p&lt;0.001). All patients initially changed to ciclosporin. 33 (46%) restarted tacrolimus at 109 days (20–228) after initial cessation. Of these, none had recurrent neurotoxicity sufficient to require further withdrawal; this cohort included 5 with previous seizures and 3 with neuroimaging confirmed PRES. Survival at 1528 (707–2218) days was similar among those who did and did not swap from tacrolimus (p=0.065). We report that cessation of initial tacrolimus immunosuppression in response to a diagnosis of neurotoxicity was relatively frequent in this cohort of liver transplant patients. Prior chronic hepatic encephalopathy was correlated with a diagnosis of neurotoxicity. Importantly, all patients in whom tacrolimus was reinitiated after cessation were able to remain on the drug long-term without recurrent major neurotoxicity.