Pre-transplant diabetes predicts atherosclerotic vascular events and cardiovascular mortality in liver transplant recipients: a long-term follow-up study


      • Liver transplant recipients show a high cardiovascular risk.
      • No validated guidelines are available for cardiovascular prevention.
      • Available studies display clear methodological limits.
      • The present study shows a very long follow-up period.
      • Pre-transplant diabetes is a strong predictor of cardiovascular events.


      Background Early after surgery, liver transplant (LT) recipients often develop weight gain. Metabolic disorders and cardiovascular disease represent main drivers of morbidity and mortality. Our aim was to identify predictors of atherosclerotic vascular events (AVE) and to assess the impact of AVE on the long-term outcome.
      Methods We retrospectively analyzed data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics. Cox Regression analysis was performed to identify predictors of AVE, global mortality, and cardiovascular mortality. Survival analysis was performed using the Kaplan-Meier method.
      Results We analyzed data from 367 subjects during a median follow-up of 14 years. Thirty-seven post-LT AVE were registered. Patients with AVE more frequently showed pre-LT diabetes mellitus (DM) (48.6 vs 13.9%, p=0.000). In the post-LT period, patients with AVE satisfied criteria of metabolic syndrome in 83.8% vs. 36.7% of subjects without AVE (p=0.000). At multivariate analysis, pre-LT DM independently predicted AVE (HR 2.250, CI 4.848-10.440, p=0.038). Moreover, both pre-LT DM and AVE strongly predicted cardiovascular mortality (HR 5.418, CI 1.060–29.183, p=0.049, and HR 86.097, CI 9.510–779.480, p=0.000, respectively).
      Conclusions Pre-LT DM is the main risk factor for post-LT AVE. Pre-LT DM and post-LT AVE are strong, long-term predictors of cardiovascular mortality. Patients with pre-LT DM should obtain a personalized follow-up for prevention or early diagnosis of AVE.



      AVE (atherosclerotic vascular event), BMI (body mass index), CI (confidence interval), CNIs (calcineurin inhibitors), CSA (cyclosporine), CV (cardiovascular), DM (diabetes mellitus), EVE (everolimus), HCC (hepatocellular carcinoma), IR (insulin resistance), LT (liver transplant), mTOR (mammalian target of rapamycin), MELD (model for end-stage liver disease), MetS (metabolic syndrome), MMF (mycophenolate mofetile), NAFLD (non-alcoholic fatty liver disease), NASH (non-alcoholic steatohepatitis), SD (standard deviation), SIR (sirolimus), TAC (tacrolimus)
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