Survival rates following liver transplantation have improved markedly in the last decade, and typically over 80% of patients are alive with a functioning graft 1 year after primary liver transplantation.1 Ongoing attrition, however, means that approximately a third of patients with a functioning graft at 1 year will have lost their graft by 10 years posttransplant.2 While disease recurrence remains a major cause of graft loss, cardiovascular events and new-onset malignancy account for more than half of non-graft-related deaths after the first year posttransplant2 and as such are an important target for improving liver transplant outcomes. Liver transplant recipients are at heightened risk of developing ischemic events or cardiovascular death compared to age- and gender-matched controls in the general population,3, 4 largely as a result of metabolic abnormalities associated with the original disease condition and immunosuppressive therapy. A careful assessment of the long-term complications associated with any immunosuppressive regimen is therefore essential in addition to a consideration of efficacy. Despite the development of a range of novel agents, use of calcineurin inhibitors remains routine in liver transplantation, but comparisons of the 2 commercially-available calcineurin inhibitors, cyclosporine microemulsion (CsA-ME) and tacrolimus, have reported conflicting results both in terms of efficacy and relative cardiovascular risk in liver transplantation.5, 6
The (LIS2T) study was a multicenter, prospective trial that compared efficacy and safety outcomes in de novo liver transplant patients randomized to CsA-ME or tacrolimus at 3, 6, and 12 months posttransplant. The trial was the first to compare tacrolimus with CsA-ME, whereby CsA-ME dose is adjusted based on cyclosporine (CsA) blood concentration at 2 hours postdose (C2). As reported previously,7 the LIS2T trial found no significant differences in efficacy (other than among hepatitis C–positive patients, in whom graft failure and death was less common with CsA-ME) or in terms of malignancy or tolerability at 6 months, except for a significantly higher incidence of diabetes mellitus and of diarrhea with tacrolimus. Data collected at 12 months regarding patient and graft survival, occurrence of acute rejection, immunosuppressive regimen, and selected safety measures including incidence of malignancy and requirement for treatment of diabetes mellitus, hyperlipidemia, and hypertension to determine whether any change in outcomes or risk profile developed after the first 6 months are presented here.