We thank Bazerbachi et al. for their editorial on our study identifying a subgroup of patients with hepatocellular carcinoma (HCC) and a very low risk of wait-list dropout; this observation may have important implications for the current organ allocation policy for liver transplantation (LT). In this study, which included only patients meeting T2 criteria (1 lesion of 2-5 cm or 2-3 lesions with none greater than 3 cm), the subgroup meeting all 3 of the following criteria had wait-list dropout rates of only 1.3% and 1.6% at 1 and 2 years, respectively: a single tumor measuring 2 to 3 cm, a complete response to the first locoregional treatment, and an alpha-fetoprotein level ≤ 20 ng/mL after the first locoregional treatment. We concluded that this subgroup (20% of our transplant patients) does not derive an immediate benefit from LT and should not receive the same listing priority as other patients with T2 HCC. Bazerbachi et al. raised the concern that the rest of the cohort without these favorable characteristics (a low alpha-fetoprotein level and a complete response to locoregional treatment) might in fact have increased posttransplant recurrence and worse survival. They also pointed out that the posttransplant outcomes of our cohort were not provided.
We have emphasized in our article that we do not advocate giving priority to patients at highest risk for dropout because these patients have been shown to have unfavorable tumor biology and worse outcomes after LT. Most, if not all, of these high-risk patients have already been selected out in our center by prolonged wait-list times. Consequently, we believe that after the exclusion of those at lowest risk for dropout, the remaining 80% of our patients represent a group at intermediate risk for dropout that would benefit from listing priority and do well after LT. To support this idea, we provide additional data on HCC recurrence and posttransplant survival for 276 patients in our cohort who underwent LT. The median post-LT follow-up was 4.4 years (interquartile range = 2.5-6.1 years). The overall recurrence-free probabilities were 95.8% and 86.8% at 1 and 5 years, respectively, and the posttransplant patient survival rates were 93.8% and 79.0% at 1 and 5 years, respectively. There was no statistically significant difference in the recurrence-free probabilities between the group with a low risk of dropout (n = 57) and all others (n = 219). For the group with a low risk of dropout, the 1- and 5-year recurrence-free probabilities were 98.2% and 92.5%, respectively, whereas the probabilities were 95.2% and 85.3%, respectively, for all others (log-rank P = 0.19; Fig. 1).
The overall 1- and 5-year survival rates for the group with a low risk of dropout were 96.5% and 94.7%, respectively, which were significantly better than those for all others (Fig. 2), but the difference could not be attributed to HCC recurrence. There were only 4 deaths among the 57 patients in the group with a low risk of dropout, and these deaths included 2 due to HCC recurrence, 1 due to HCV recurrence, and 1 due to an infection. The most common causes of death for all others (49 deaths among 219 patients) were HCC recurrence (38.8%), infection (18.4%), HCV recurrence (12.2%), non-HCC malignancies (10.2%), and non–HCV-related graft dysfunction (10.2%). The 1- and 5-year overall survival rates of 93.1% and 75.1% for all others compare favorably with published United Network for Organ Sharing data for all HCC patients undergoing transplantation within T2 criteria. These findings suggest that excluding patients with a very low risk of wait-list dropout from LT does not mean that we would instead perform transplantation for patients with a high risk of posttransplant HCC recurrence and poor survival. Rather, this approach may represent a step forward in trying to achieve equitable dropout rates for HCC and non-HCC patients.
Neil Mehta, M.D.1
Jennifer L. Dodge, M.D.2
John Paul Roberts, M.D.2
Ryutaro Hirose, M.D.2
Francis Y. Yao, M.D.1,2
Departments of 1Medicine (Division of Gastroenterology) and 2Surgery (Division of Transplant Surgery)
University of California San Francisco
San Francisco, CA