In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (−3.0%; 95% CI −8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m2, 97.5% CI 3.74, 13.27 mL/min/1.73 m2, p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.

Among patients who successfully completed 1 yr of intense dietary intervention, nine of 15 patients with NASH displayed histologic improvement. This pilot study suggests that dietary intervention can be effective in improving histology in patients with biopsy-proven NASH.

In a 24‐month prospective, randomized, multicenter, open‐label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy‐proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference −2.2%, 97.5% confidence interval [CI] −8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m2 (97.5% CI 1.9, 11.4 mL/min/1.73 m2, p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m2 in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m2 in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced‐exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.

Background-In order to receive a liver transplant, patients must first be placed on the waiting list -a decision made in most transplant centers by a multidisciplinary committee. The function of these committees has never been studied.