Background

Early allograft dysfunction (EAD) after living donor liver transplantation (LDLT) has often been attributed to inadequate graft size, and termed small-for-size syndrome. Early allograft dysfunction definitions include a variable constellation of findings, including hyperbilirubinemia, coagulopathy, encephalopathy, and ascites formation. Among putative causes of EAD after LDLT are excessive portal pressure and/or flow. Our objective was to evaluate patterns of EAD after LDLT.

Methods

In this study, 631 LDLT recipients were monitored for complications, EAD (defined by postoperative day 7 bilirubin >10 mg/dL or international normalized ratio >1.6), and graft failure. Approximately 200 had portal venous and arterial pressure and flow measurements before and after LDLT. Portal inflow modification (splenic artery ligation, hemiportocaval shunt, or splenectomy) was performed at the discretion of the operating surgeon. Associations between EAD and recipient, donor, and transplant factors were examined using multivariable logistic regression.

Results

Risk of EAD was associated with left lobe grafts, lower graft weight among left lobes, higher preoperative bilirubin, higher portal reperfusion pressure, higher donor age, and higher donor body mass index. The risk of graft loss within the first 90 days was 5.2 times higher for recipients with EAD versus those without EAD (P < 0.001).

Conclusions

Early allograft dysfunction can be defined using postoperative day 7 laboratory values that are highly predictive of early graft failure within 90 days. Risk factors associated with EAD after LDLT include: graft type and size, preoperative bilirubin, portal reperfusion pressure, donor age, and donor body mass index.

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.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long-term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer-related factors on multivariable analysis. A dose-response effect of age on survival was observed, with every 5-year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non-HCC-related mortality (P = 0.004), and not HCC-related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single-center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer-related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non-HCC-related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.