Comparative cohort study between the outcome of living donor liver transplant in patients with hepatocellular carcinoma within and beyond Milan criteria

Background
Liver transplantation has been accepted as an effective therapy for hepatocellular carcinoma (HCC). The Milan criteria is widely used across the world to select liver transplantation candidates in patients with HCC. However, the Milan criteria may be too strict because a substantial subset of patients who have HCC exceed the criteria, who would benefit from liver transplant, and may be unnecessarily excluded from the waiting list. In recent years, many extended criteria beyond the Milan criteria have been presented, which were proven to be able to yield similar outcomes compared with those patients meeting the Milan criteria. Because the simple use of the tumor’s size and number was insufficient to indicate HCC biological features and to predict the risk of tumor recurrence, it was unrealistic to rely only on these two criteria to exclude a patient from transplant service.
Purpose
To fortify the principle of using University of California San Francisco criteria (UCSF) and ‘up to seven’ criteria for indicating patients with HCC for transplant and thus providing a wider inclusion scope for patients with HCC in transplant service, which would provide a potentially curative solution for previously excluded potentially curable patients.
Patients and methods
This is a retrospective comparative cohort study. Our study was performed in Egypt by comparing the outcome of patients with HCC transplanted from living donors within Milan criteria and those who are beyond Milan criteria, but within the University of California San Francisco criteria or up to seven criteria who responded to down-staging therapy and included back within Milan criteria in terms of recurrence rate and mortality and recurrence free. The study was performed in Air Force specialized hospitals and Nasser Institute in Cairo in the period from July 2015 to November 2021.
Results
The total study sample size was 70 patients. Overall, 72.9% (=51) of them were transplanted in Air Force specialized hospitals, whereas 27.1% (=19) in Nasser Institute. The study group was subdivided according to the listing criteria for transplant; 61.4% (=43) were under the Milan criteria, whereas 38.6% (=27) were listed under the University of California San Francisco criteria or ‘up to seven’ criteria (beyond Milan criteria group). The posttransplant HCC recurrence was detected in 4.7% (=2) in the Milan criteria group, whereas in six (22.2%) patients of the beyond Milan criteria group (=0). By comparing survival rates, the Milan criteria group’s survival rates on 1-, 3-, 5-year follow-up were 90.6, 86, and 86%, respectively, whereas the rates were 92.5, 88.8, and 88.8% in the beyond Milan criteria group. The mean survival time in the Mila criteria group was 62.6 months compared with 65.28 months in the beyond Milan criteria group (=0.6). The posttransplant recurrence free rates were 90.6, 83, and 83% in 1-, 3-, and 5-year follow-up in the Milan group, when analyzed in the beyond Milan criteria group, they were found to be 88.8, 77.7, and 74% in the same follow-up intervals, with value of 0.566. This demonstrated comparable survival rates and recurrence-free rates between the two groups.
Conclusion
Efficient downstaging therapy has rendered the UCSF criteria and the ‘up to seven’ criteria more usable than before for including patients with HCC for the transplant service as they have been proven to have tumor recurrence rate, survival time, and tumor-free survival time comparable to the Milan criteria. Hence, they provide the curative benefit of liver transplant for a wider scope of patients with HCC.