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Multicenter Study
. 2021 Sep 1;156(9):e213112.
doi: 10.1001/jamasurg.2021.3112. Epub 2021 Sep 8.

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

Quirino Lai  1   2 , Gonzalo Sapisochin  3 , Andre Gorgen  3 , Alessandro Vitale  4 , Karim J Halazun  5   6 , Samuele Iesari  1 , Benedikt Schaefer  7 , Prashant Bhangui  8 , Gianluca Mennini  2 , Tiffany C L Wong  9 , Shinji Uemoto  10 , Chih-Che Lin  11 , Jens Mittler  12 , Toru Ikegami  13 , Zhe Yang  14 , Anna Chiara Frigo  15 , Shu-Sen Zheng  14 , Yuji Soejima  13 , Maria Hoppe-Lotichius  12 , Chao-Long Chen  11 , Toshimi Kaido  10 , Chung Mau Lo  9 , Massimo Rossi  2 , Arvinder Singh Soin  8 , Armin Finkenstedt  7 , Jean C Emond  5   6 , Umberto Cillo  4 , Jan Paul Lerut  1
Affiliations
Multicenter Study

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

Quirino Lai et al. JAMA Surg. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Sapisochin reported receiving grants from Bayer and Roche outside the submitted work as well as personal fees from Integra, Novartis, and AstraZeneca. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Patients in the International and Toronto Cohorts
DDLT indicates deceased-donor liver transplant; HCC, hepatocellular carcinoma; LDLT, living-donor liver transplant; LT, liver transplant.
Figure 2.
Figure 2.. Intention-to-Treat Patient Survival Rates Before and After Inverse Probability of Treatment Weighting (IPTW) in the International Cohort (A and B) and Toronto Cohort (C and D)
DDLT indicates deceased-donor liver transplant; LDLT, living-donor liver transplant.
See this image and copyright information in PMC

Comment in

References

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