Neuropsychiatric Symptoms After Liver Transplant for Wilson's Disease: A US-Based Multicenter Retrospective Cohort...

Liver transplantation (LT) is the standard treatment for Wilson disease (WD) with end-stage liver failure, but its use for severe neurological symptoms remains controversial due to reports of paradoxical post-transplant deterioration. This study examines the risk and predictors of neuropsychiatric symptoms after LT for WD compared to other liver diseases. We conducted a retrospective cohort study using the TriNetX US Collaborative Network. WD patients who underwent LT were matched 1:1 with non-WD LT recipients using propensity score matching (PSM) based on demographics, comorbidities, laboratory values, and immunosuppressant use. Cox proportional hazards models assessed the 5-year risk of composite neuropsychiatric symptoms (defined as the occurrence of any seizure disorder, movement disorder, mood or anxiety disorder, insomnia, cognitive deficit, neuromuscular disorder, psychotic disorder, or delirium) as well as specific symptom components and identified predictors in the LT/WD group. Among 484 LT/WD and 88 486 LT/non-WD patients (475 per group post-PSM), WD patients had higher rates of the composite and several specific neuropsychiatric symptoms, including tremors, anxiety, insomnia, mood disorders, and myoneural junction disease. After PSM, the composite neuropsychiatric symptoms remained significantly elevated in LT/WD patients (HR 1.3, p = 0.007). Predictors in LT/WD included Asian race (HR 2.0, p = 0.04), diabetes (HR 1.9, p < 0.001), smoking (HR 1.8, p = 0.03), and cyclosporine-based immunosuppression compared with non-cyclosporine regimens (HR 2.5, p = 0.007). Patients with WD undergoing LT face a higher long-term risk of neuropsychiatric symptoms compared with non-WD recipients. Identification of high-risk subgroups and potentially modifiable factors, including immunosuppressive regimen selection, may inform post-transplant surveillance and management strategies.