Defining long-term outcomes with living donor liver transplantation in North America

Abstract

Objectives: To compare long-term survival of living donor liver transplant (LDLT) at experienced transplant centers with outcomes of deceased donor liver transplant and identify key variables impacting patient and graft survival.

Background: The Adult-to-Adult Living Donor Liver Transplantation Cohort Study is a prospective multicenter National Institutes of Health study comparing outcomes of LDLT and deceased donor liver transplant and associated risks.

Methods: Mortality and graft failure for 1427 liver recipients (963 LDLT) enrolled in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study who received transplant between January 1, 1998, and January 31, 2014, at 12 North American centers with median follow-up 6.7 years were analyzed using Kaplan-Meier and multivariable Cox models.

Results: Survival probability at 10 years was 70% for LDLT and 64% for deceased donor liver transplant. Unadjusted survival was higher with LDLT (hazard ratio = 0.76, P = 0.02) but attenuated after adjustment (hazard ratio = 0.98, P = 0.90) as LDLT recipients had lower mean model for end-stage liver disease (15.5 vs 20.4) and fewer received transplant from intensive care unit, were inpatient, on dialysis, were ventilated, or with ascites. Posttransplant intensive care unit days were less for LDLT recipients. For all recipients, female sex and primary sclerosing cholangitis were associated with improved survival, whereas dialysis and older recipient/donor age were associated with worse survival. Higher model for end-stage liver disease score was associated with increased graft failure. Era of transplantation and type of donated lobe did not impact survival in LDLT.

Conclusions: LDLT provides significant long-term transplant benefit, resulting in transplantation at a lower model for end-stage liver disease score, decreased death on waitlist, and excellent posttransplant outcomes. Recipient diagnosis, disease severity, renal failure, and ages of recipient and donor should be considered in decision making regarding timing of transplant and donor options.Clinical Trials ID: NCT00096733.

Figures

Figure 1

Survival plots of mortality and graft failure by transplant type. Panels (a) and (b) show unadjusted and adjusted probability of freedom from death. Panels (c) and (d) show unadjusted and adjusted probability of graft survival. Adjusted survival probabilities are presented for a 53 year old male patient without non-HCC malignancy or PSC, not dialysis at transplant, MELD of 16, and received a liver from a donor under 50 years old. Adjusted graft survival probabilities are presented for a 53 year old patient without autoimmune hepatitis, HCC, or PSC, a MELD of 16 at transplant, and not on dialysis at transplant, and received a liver from a donor under 50 years old. HCC=hepatocellular carcinoma, PSC=primary sclerosing cholangitis, MELD=model for end-stage liver disease.

Figure 2

Unadjusted cumulative incidence for specific causes of death by transplant type. The number of deaths in each group due to each specific cause and p-values from tests of differences between unadjusted cumulative incidence functions for LDLT vs. DDLT are shown on the right. MSOF=multiple system organ failure.

Figure 3

Unadjusted cumulative incidence for causes of graft failure (summarized as re-transplant or death without re-transplant) by transplant type.

Figure 4

Forest plots showing estimated hazard ratios on the log scale for covariate effects associated with (a) patient mortality and (b) graft failure from separate Cox models for LDLT (grey boxes) and DDLT (black boxes) recipients; whiskers show 95% confidence intervals for true log hazard ratios. P-values are from tests of interaction between each covariate and LDLT/DDLT in a combined model. Note all p-values >0.05 imply no significant differences in log hazard ratios between LDLT and DDLT.