Efficacy and Safety of Everolimus With Reduced Tacrolimus in Liver Transplant Recipients: 24-month Results From the Pooled Analysis of 2 Randomized Controlled Trials.

BACKGROUND AND METHODS: Data from 2 randomized liver transplant trials (N = 772; H2304 [deceased donor, n = 488], H2307 [living donor, n = 284]) were pooled to further evaluate the efficacy and safety of everolimus with reduced tacrolimus (EVR + rTAC) versus standard tacrolimus (sTAC) regimen at month 24. RESULTS: EVR + rTAC was comparable to sTAC for composite efficacy failure of treated biopsy-proven acute rejection, graft loss, or death (9.8% versus 10.8%; difference, -1.0%; 95% confidence interval, -5.4 to 3.4; P = 0.641) at month 24. EVR + rTAC was superior to sTAC for the mean change in estimated glomerular filtration rate (eGFR) from randomization to month 24 (-8.37 versus -13.40 mL/min/1.73 m2; P = 0.001). A subanalysis of renal function by chronic kidney disease (CKD) stage at randomization showed significantly lower decline in eGFR from randomization to month 24 for patients with CKD stage 1/2 (eGFR ≥ 60 mL/min/1.73 m2) in EVR + rTAC group versus sTAC (-12.82 versus -17.67 mL/min/1.73 m2, P = 0.009). In patients transplanted for hepatocellular carcinoma (HCC) beyond Milan criteria, HCC recurrence was numerically lower although not statistically significant with EVR + rTAC versus sTAC group (5.9% [1 of 17] versus 23.1% [6 of 26], P = 0.215), while comparable in patients within Milan criteria (2.9% [3 of 102] versus 2.1% [2 of 96], P = 1.000), irrespective of pretransplant alpha-fetoprotein levels. CONCLUSIONS: EVR + rTAC versus sTAC showed comparable efficacy and safety with significantly better renal function, particularly in patients with normal/mildly decreased renal function (CKD stage 1/2) at randomization and a trend toward lower HCC recurrence in patients transplanted with HCC beyond Milan at month 24. Further long-term data would be required to confirm these results.

Readdressing the Middle Hepatic Vein in Right Lobe Liver Donation: Triangle of Safety.

For equipoising donor safety and optimal recipient outcomes, we adopted an algorithmic "triangle of safety" approach to retrieve 3 types of right lobe liver grafts (RLGs), namely, the modified extended right lobe graft (MERLG), the partial right lobe graft (PRLG), and the modified right lobe graft (MRLG). Reconstruction to achieve a single wide anterior sector outflow was ensured in all patients. We present donor and recipient outcomes based on our approach in 665 right lobe (RL) living donor liver transplantations (LDLTs) performed from January 2013 to August 2015. There were 347 patients who received a MERLG, 117 who received a PRLG, and 201 who received a MRLG. A right lobe graft (RLG) with a middle hepatic vein was retrieved only in 3 out of 18 donors with steatosis >10%. Cold ischemia time was significantly more and remnant volume was less in the MRLG group. Of the donors, 29.3% had complications (26% Clavien-Dindo grade I, II) with no statistically significant difference among the groups. The Model for End-Stage Liver Disease score was higher in the MERLG group. There were 34 out of 39 with a graft-to-recipient weight ratio (GRWR) of <0.7% who received a MERLG with inflow modulation. Out of 4 patients who developed small-for-size syndrome in this group, 2 died. The 90-day patient survival rate was similar among different GRWRs and types of RLG. In conclusion, a selective and tailored approach for RL donor hepatectomy based on optimal functional volume and metabolic demands not only addresses the key issue of double equipoise in LDLT but also creates a safe path for extending the limits.