Abstract and Introduction
Abstract
Hepatocellular carcinoma (HCC) represents an increasing fraction of liver transplant indications; the role of living donor liver transplant (LDLT) remains unclear. In the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, patients with HCC and an LDLT or deceased donor liver transplant (DDLT) for which at least one potential living donor had been evaluated were compared for recurrence and posttransplant mortality rates. Mortality from date of evaluation of each recipient's first potential living donor was also analyzed. Unadjusted 5-year HCC recurrence was significantly higher after LDLT (38%) than DDLT (11%), (p = 0.0004). After adjustment for tumor characteristics, HCC recurrence remained significantly different between LDLT and DDLT recipients (hazard ratio (HR) = 2.35; p = 0.04) for the overall cohort but not for recipients transplanted following the introduction of MELD prioritization. Five-year posttransplant survival was similar in LDLT and DDLT recipients from time of transplant (HR = 1.32; p = 0.27) and from date of LDLT evaluation (HR = 0.73; p = 0.36). We conclude that the higher recurrence observed after LDLT is likely due to differences in tumor characteristics, pretransplant HCC management and waiting time.
Introduction
Liver transplantation (LT) is a well-established therapeutic option in patients with unresectable hepatocellular carcinoma (HCC). The rate of recurrent HCC had been reported to be significantly higher following living donor liver transplant (LDLT) compared to deceased donor liver transplant (DDLT), even after adjustment for tumor stage. The reasons for this observation remain speculative. In the United States, enhanced prioritization for DDLT for candidates with HCC is limited to those fulfilling the Milan criteria, leaving LDLT as the only timely route to transplantation without the delay and uncertainty of downstaging for those with more advanced lesions. Anticipated prolonged waiting times for DDLT, with the risk of drop out due to tumor progression, may also provide motivation to pursue LDLT. Differences in expected waiting times in DDLT and LDLT can influence pretransplant management, specifically resulting in less application of loco-regional therapies (LRT) prior to LDLT due to shorter waiting times.
The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) consortium previously reported a 3-year HCC recurrence probability of 29% following LDLT versus 0% following DDLT in a cohort of 92 recipients (p = 0.002). The majority of these patients (57%) were transplanted prior to the introduction of Model for End-Stage Liver Disease (MELD). Since the publication of our original report, the number of HCC patients who have undergone transplantation in the A2ALL study has more than doubled, and the median duration of follow-up following transplant has increased from 3.7 to 4.9 years. Moreover, the results reported in the earlier study were derived largely from a retrospective cohort. The main aims of this study were to compare recurrence and mortality following LDLT or DDLT. We also analyzed survival from the time of the donor's evaluation in an intention-to-treat analysis among those who had at least one potential living donor evaluated; we compared those who underwent LDLT versus those who did not receive an LDLT (LDLT candidates who received a DDLT plus those who had a potential living donor evaluated but were not transplanted at all).