Changes in lipid and carbohydrate metabolism under mTOR- and calcineurin-based immunosuppressive regimen in adult patients after liver transplantation.

BACKGROUND: Cardiovascular disease is a leading cause of long-term mortality after liver transplantation (LT). Life long immunosuppression harbors the risk of metabolic alterations. We aimed to analyze the impact of calcineurin (CNI)-only containing regimen (group A) compared to mTOR-containing regimen (group B) on lipid and carbohydrate metabolism.

PATIENTS/METHODS: 92 adult patients after LT, University of Mainz (group A-78 patients, group B-14 patients; 65 M/27 F; mean age 59+/-10.2years; mean time from LT 5.8+/-5years). Clinical data, comorbidities, and medication were assessed. Fasting lipid profile including small dense LDLs (sdLDL) and oral glucose tolerance tests were performed.

RESULTS: Group B had significantly higher levels of total cholesterol (TC), LDL-cholesterol (LDL-C), triglycerides (TG) and sdLDL, with persistence of higher TC, TG, sdLDLs (mg/dl) after exclusion of patients under lipid lowering medication. Concentrations above the upper limits of normal were found: for LDL-C in 9% of group A/35.7% of group B (p=0.016); for TG: in 32.1% of group A/92.9% in group B (p=0.0001). A positive correlation between time since LT (years) and sdLDL (mg/dl) was found in group B (p=0.018). In patients without previously known diabetes, NODAT and impaired glucose tolerance developed in 27.9% of group A/44.4% of group B (n.s.).

CONCLUSION: Patients under mTOR-containing regimen are at higher risk to develop dyslipidemia with increased atherogenic sdLDLs compared to patients under CNI-only-containing regimen and display more frequently a dysglycemic status, with uncertain relevance for long-term cardiovascular risk. A careful monitoring after LT is needed to identify early metabolic risk and manage this appropriately.