Evaluation of the Intention-to-Treat Benefit of Living Donation in Patients With Hepatocellular Carcinoma Awaiting a Liver Transplant.

Importance: Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC). Objective: To investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription. Design, Setting, and Participants: This multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020. Main Outcomes and Measures: Intention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created. Results: A total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated. Conclusions and Relevance: This study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.

Extended criteria for liver transplantation in hepatocellular carcinoma. A retrospective, multicentric validation study in Belgium.

BACKGROUND: Recent studies indicate that a group of patients with cirrhosis receiving a liver transplantation for hepatocellular cancer (HCC) beyond the Milan Criteria (MC) can achieve a similar outcome compared to patients within these criteria. This study aims to investigate the value of the Asan critera (AC), up-to-7 criteria (UT7), French alpha-foetoprotein (AFP) model and Metroticket 2.0 (MT2.0) model compared to the MC. METHODS: 526 patients transplanted for non-metastatic HCC were analyzed. Patient groups within and beyond MC and extended criteria were determined according to radiological assessment and AFP value at listing. RESULTS: Overall survival (OS) and recurrence (RR) rates were similar between patients within MC and all extended criteria. Five-year OS within MC was 71.3% compared to 70.9% for AC, 71.4% for UT7, 69.7% for AFP-model and 71.0% for MT2.0 criteria. Five-year RR within MC was 12.3% compared to 13.5% for AC, 13.0% for UT7, 14.3% for AFP-model and 13.2% for MT2.0 criteria. Patients beyond MC but within the extended criteria had tendency towards higher recurrence. CONCLUSIONS: All validated extended criteria (AC, UT7, AFP-model and MT2.0) could be proposed as alternatives to the MC with similar outcome. Prospective data are awaited to assess recurrence beyond MC.