Results
Demographics, Transplant and HCC Characteristics
During the period of study, 283 patients initially met the inclusion criteria, were selected as potential candidates and were listed for LT. A total of 199 patients underwent LT, 52 patients were removed from the waiting list during the time of the study and 32 of those candidates remained on the list at the end of the analysis.
The median waiting time for LT for the entire cohort was 4.9 months (3.2 for first quartile–8.2 months for third quartile). The waiting time also remained stable according to blood type. Mean follow-up after LT of the entire cohort of study was 1.7 years (6 months–6.7 years).
The demographic and radiological characteristics of the candidate and transplant recipients who entered the study were similar to most studies of HCC patients (Table 1). There was a preponderance of white, middle-aged males with hepatitis C virus with a low biological MELD score. These characteristics were equivalent for all groups of the study, for listed and transplanted patients. The median DRI was 1.5.
Patients presented with one to two nodules, the largest being 29 mm. Most patients (85%) underwent TACE (1.5 Sessions) and were considered responders. The number of TACE sessions increased according to the time on the waiting list. The other pretransplant characteristics were equivalent within all groups of the study.
Dropout From the Waiting List
During the study period 52 patients (16.1%) were removed from the waiting list. The dropout rates at 3-, 6-, and 12-months were 6.4%, 12.4%, and 17.7%, respectively. Dropout rates remained stable during the interval of the study. Among the patients with HCC removed from the list, 40 (85.1%) were removed due to HCC progression beyond the MC. Patients who dropped out from the waiting list differed from successful transplant candidates on blood type (A and O more often dropped out) and response to TACE.
Mortality on the List, Transplant Rate and Posttransplant Death
Figure 1 depicts the pre and posttransplant mortality according to time on the list. The chance of receiving an allograft grows over time, reaching ~90% of those who waited longer than 9-months on the list. Overall mortality on the list was 4.83% (13 deaths in 283 patients), but varied tremendously depending of the time on the list. Those who waited less than 6-months had a higher risk of death on the list than those who waited longer than 6-months Figure 2.
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Figure 1.
Cumulative incidence of pre and posttransplant according to time on the list (n = 283). Time zero on the graphic was considered the date of inclusion of the patient the list.
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Figure 2.
Adjusted overall survival according to the waiting list (entire cohort, n = 283).
Overall survival according to waiting time on the list is detailed in Figure 3. Patients who waited less than 3-months had an inferior survival when compared to the other groups (p = 0.027).
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Figure 3.
Unadjusted overall survival (entire cohort, n = 283). MELD, Model for end stage liver disease; AFP, alpha-phetoprotein; TACE, Transarterial chemoembolization; HCC, hepatocellular carcinoma.
Factors Influencing Survival and the Impact of Waiting Time on Survival
For all candidates included in the study, female sex, age of the recipient, multinodular disease, HCC within MC, times on the list and MELD at transplant were selected as potential risk factors for mortality in the univariate analysis. Prolonged time on the list significantly reduced mortality in this analysis (p = 0.02, HR = 0.28). Biological MELD at transplantation did also independently impact overall survival (p = 0.03, HR = 1.06, Table 2). AFP, tumor size, and response to TACE did not exert a major effect on survival (Figure 3).
Demographics of Transplant Recipients, Stage, Transplant Characteristics, and Pathology Data
The demographics of patient who underwent liver transplantation were not different than those who entered the list at the beginning of the study (Table 3). Most explants were under MC and without microvascular invasion. The majority of patients was classified on stage A of the Barcelona Cancer Liver Clinic (89.8%) and on stages I (50.3%) or II (45.9%) of the American Joint Committee on Cancer (AJCC) TNM Staging for Liver Tumors.
Impact of Other Variables on Posttransplant Survival of Patients With Long Waiting List Time
Female sex, age, HCC within MC and MELD at transplant were found to be significant risk factors on univariate analysis (p < 0.2). MELD was the only factor that independently impacted post-transplant survival (p = 0.048, HR = 1.05, Table 4) in the multivariate analysis.