LIVER EXPERT FORUM –
LIVER EXPERT FORUM – CONFERENCE REPORT Graft survival Patient survival Survival probability 1.0 0.8 0.6 0.4 0.2 0.0 Thymoglobulin Basiliximab Log rank p=0.029 Survival probability 1.0 Thymoglobulin 0.8 Basiliximab 0.6 0.4 Log rank p=0.024 0.2 0.0 1 2 4 6 8 10 1 2 4 6 8 10 Time post-transplant (years) Time post-transplant (years) Figure 3. Graft survival and patient survival among primary liver transplant patients given rATG induction (n=322) or basiliximab induction (n=273), both with tacrolimus (and MMF in patients with renal dysfunction) based on a retrospective single-center analysis [24] EDUCATION tion, there was a strong trend towards superior outcomes with rATG/ATG versus IL-2RA therapy [18,19]. Induction and steroid-free immunosuppression Reviewing the available data, Prof. Silvio Nadalin (Tübingen, Germany) noted that the risk of biopsy-proven acute rejection (BPAR) after liver transplantation is substantially increased with steroid-free immunosuppression (i.e. no oral steroids) in the absence of induction [20]. As a result, either rATG or basiliximab is generally given to support steroid-free therapy. Randomized trials have shown that a steroid-free combination of IL-2RA induction with tacrolimus and mycophenolate mofetil (MMF) achieves a lower rate of BPAR, or a lower requirement for steroid therapy to manage rejection, than standard tacrolimus/ steroid therapy [22–24]. One retrospective study that compared rATG versus basiliximab in 595 primary liver transplant patients given steroid-free “Where steroid-free therapy is planned, induction is generally adopted to maintain immunosuppressive potency.” therapy (both with tacrolimus from day 4, accompanied by MMF in patients with renal dysfunction) found BPAR to be less frequent at final follow-up 52
LIVER EXPERT FORUM – CONFERENCE REPORT 0,4 8 % 17 % 22 % Cumulative incidence of chronic renal failure 0,3 0,2 0,1 0,0 0 1 2 3 4 5 6 Time post-transplant (years) Figure 4. Cumulative incidence of chronic renal failure in 221 patients receiving a liver transplant at a single center during 2002–2007 [25] in the rATG group (18% versus 27%) [24]. The same analysis found graft survival and patient survival to be significantly higher in rATG-treated patients (Figure 3), a finding that was confirmed on multivariate analysis (graft loss: hazard ratio 0.61 [95% CI 0.38, 0.97]; death: hazard ratio 0.64 [95% CI 0.41, 1.01]) [24]. Renal dysfunction and calcineurin inhibitor therapy: A remit for induction Progressive loss of renal function after liver transplantation is widespread (Figure 4) [25]. As many as 10–20% of patients experience endstage renal disease by five years post-transplant [25,26]. Prof. Wolfgang Bechstein (Frankfurt, Germany) highlighted that one of the few modifiable risk factors for renal dysfunction is CNI-related nephrotoxicity, which distorts renal architecture even in the current era of low-exposure tacrolimus therapy [27]. CNI therapy is estimated to increase the risk of chronic renal dysfunction after liver transplantation by more than two-fold [28]. CNI-sparing regimens after liver transplantation have been investigated in an attempt to preserve long-term kidney function. Prof. Hans Schlitt (Regensburg, Germany) reviewed three possible approaches – delayed initiation of CNIs, reduced-exposure CNI and CNI withdrawal – and the need for induction with each strategy. Delayed CNI initiation Studies have shown that when accompanied by IL-2RA induction [29–31], delaying introduction of CNI therapy to day 4 or 5 post-transplant does not compromise immunosuppressive efficacy and can EDUCATION 53
