Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium.
General Surgery and Organ Transplantation Unit, Department of General 3 Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy.
JAMA Surg. 2021 Sep 1;156(9):e213112. doi: 10.1001/jamasurg.2021.3112. Epub 2021 Sep 8.
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).
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.
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.
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.
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.
与尸体供肝肝移植（DDLT）相比，活体供肝肝移植（LDLT）在改善治疗意向结局和管理尸体供肝供体短缺方面具有优势。然而，对于 HCC 患者 LDLT 的结局仍存在相互矛盾的数据。
从等待名单登记开始，研究 LDLT 对 HCC 患者潜在生存获益的影响。
设计、地点和参与者：本研究采用意向治疗设计的多中心队列研究，分析了年龄在 18 岁或以上、患有 HCC 并在等待首次移植的患者的数据。来自欧洲、亚洲和美国的 12 个合作中心的患者构成了国际队列，这些患者于 2000 年 1 月 1 日至 2017 年 12 月 31 日期间在移植等待名单上。多伦多队列由加拿大安大略省多伦多市的 1 个移植中心的患者组成，这些患者于 2000 年 1 月 1 日至 2015 年 12 月 31 日期间在等待名单上。国际队列中心进行 LDLT 或 DDLT，而多伦多队列中心则选择同时进行 LDLT 和 DDLT。在进行逆概率治疗加权（IPTW）分析之前和之后，在这两个队列中测试了 LDLT 的获益。数据于 2020 年 2 月 1 日至 5 月 31 日进行分析。
意向性治疗死亡定义为任何原因导致的患者死亡，从肝移植等待名单登记到最后随访日期（2019 年 12 月 31 日）计算。创建了四个用于意向性治疗死亡的多变量 Cox 比例风险回归模型。
国际队列共分析了 3052 例患者，其中 2447 例为男性（80.2%），首次转诊时的中位（IQR）年龄为 58（53-63）岁。多伦多队列包括 906 例患者，其中 743 例为男性（82.0%），首次转诊时的中位（IQR）年龄为 59（53-63）岁。在所有环境中，LDLT 是一个独立的保护因素，在前 IPTW 分析中，国际队列的总体死亡风险降低了 49%（HR，0.51；95%CI，0.36-0.71；P<0.001），在后 IPTW 分析中，国际队列的总体死亡风险降低了 33%（HR，0.67；95%CI，0.53-0.85；P=0.001），在前 IPTW 分析中，多伦多队列的总体死亡风险降低了 43%（HR，0.57；95%CI，0.45-0.73；P<0.001），在后 IPTW 分析中，多伦多队列的总体死亡风险降低了 48%（HR，0.52；95%CI，0.42-0.65；P<0.001）。在所有纳入 LDLT 的情况下，数学模型的区分能力进一步提高。
本研究表明，对于等待肝移植的 HCC 患者，如果有潜在的活体供者，可能会降低意向性治疗死亡的风险。这种获益与消除脱落风险有关，并且在同时提供 LDLT 和 DDLT 选择的中心中也有报道。
