Cognitive Evaluation in Liver Transplant Patients Under Calcineurin Inhibitor Maintenance Therapy

Abstract

BackgroundNeurological disorders due to calcineurin inhibitor (CNI) treatment pose a well-known problem after liver transplantation (LTx). In this study, the impact of CNIs on cognitive functioning during maintenance therapy was analyzed. A possible improvement of cognitive functioning, compliance and health-related quality of life (HRQoL) after conversion to a once-daily tacrolimus formulation was prospectively assessed.MethodsIn a cross-section analysis cognitive functioning of living donors (LD), waiting list patients and LTx patients was tested using a 4 times trail making test (4-TTMT). In a further investigator-initiated trial a possible improvement of cognitive functioning, HRQoL and compliance after conversion to the once-daily tacrolimus formulation was prospectively assessed over 1 year. HRQoL was assessed using an EORTC-QLQ C30 questionnaire and patient’s compliance was assessed by the Basel Assessment of Compliance with Immunosuppressive Medication Scales questionnaire. Correlated data were sex, age, time after surgery, liver disease, model of end-stage liver disease score, creatinine, CNI type, and CNI trough levels.ResultsTwo hundred eleven patients were included in this cross-section analysis. Twenty-seven patients agreed to participate in the investigator-initiated trial. LTx patients completed the 4-TTMT slower than living donor patients and faster than waiting list patients. Patients with twice daily cyclosporine A (CSA) formulation needed longer to finish the 4-TTMT than patients with the once-daily tacrolimus formulation. After drug conversion of a twice-daily CNI formulation to a once-daily tacrolimus formulation, CSA-treated patients needed longer to improve their cognitive functioning. HRQoL and compliance did not improve after drug conversion.ConclusionsPatients with once-daily tacrolimus formulation had a better psychomotor speed than CSA-treated patients. The conversion to once-daily tacrolimus formulation significantly improved cognitive functioning, but had no impact on HRQoL or compliance.

Impact of Immunosuppression on Executive Functioning After Pediatric Liver Transplantation

“…In contrast to the study by Heits et al (13), in our crosssectional analysis patients on twice-daily Tac did not score better than patients on CyA. However, differences in age, primary diseases, and time from transplantation make it difficult to compare these 2 studies directly.…”

“…In 2017, Heits et al published a pilot study on 22 liver transplanted adults who were switched from either twice daily Tac or twice daily CyA to once daily Tac. Results of an adult trail‐making test improved significantly 6 and 12 months after the switch (13). In our study, we examined the potential influence of different CNI preparations in a 2‐fold manner: cross‐sectional comparison of executive functioning between patients on twice‐daily CyA, twice‐daily Tac, and once‐daily Tac revealed patients with twice‐daily Tac to score significantly worse than both patients on CyA and once‐daily Tac.…”

“…In contrast, choice of calcineurin‐inhibitor (CNI) did not influence cognitive functioning in another study on 44 liver‐transplanted children (12). In adults, executive functioning improved after switch to a once‐daily slow‐release Tac preparation (13). A more recent study that compared neurotoxicity and psychometric functioning in long‐term survivors of adult liver transplantation found that cumulative Tac dose and length of standard dose CNI therapy were negatively correlated with cognitive test results (14).…”

<p>Improving Patient Outcomes Following Pediatric Liver Transplant: Current Perspectives</p>

“…Other strategies include modifications to immunosuppressive regimens which can have detrimental effects on neurodevelopmental outcomes. 40 For example, glucocorticoids have long been implicated in growth failure and poor musculoskeletal development. 41 This is another reason why there is fairly wide acceptance of steroid-free or minimization protocols post liver transplant in children.…”

Quality of Life in Patients With Progressive Familial Intrahepatic Cholestasis

“…Interestingly, the PEBD group showed no impairment in school functioning, despite having a similar history of cholestatic liver disease. One possible explanation might be the impact of calcineurin inhibitors, which are known to affect the cognitive functioning of children after LTx (22).…”