Living-Donor Liver Transplant Is an Independent Protective Factor of Reduced Mortality in Patients With HCC

Liver cancer cells. Coloured scanning electron micrograph (SEM) of two hepatocellular carcinoma (HCC) cells, showing the numerous filopodia (hair-like) covering their surface. Hepatocellular carcinoma is the most common type of liver cancer. It tends to occur in livers damaged by genetic defects, alcohol abuse, or chronic infection with diseases such as hepatitis B and C. Primary liver cancer, which starts in the liver, is relatively rare in the UK, with about 3,600 people diagnosed each year. However, because of the prevalence of hepatitis caused by contagious viruses, it accounts for up to half of all cancers in some undeveloped countries. Magnification: x3000 when printed at 10 centimetres wide.
Investigators assessed the benefit of a potential living donor on survival in patients with hepatocellular carcinoma on a waiting list for a liver transplant.

Having a potential live donor could decrease the intention-to-treat risk of death in patients with hepatocellular carcinoma (HCC) who are on a waiting list for a liver transplant, according to a study in JAMA Surgery.

The multicenter, retrospective cohort study with an intention-to-treat design investigated data from patients aged ≥18 years with HCC who were on a waiting list for a first transplant.

The international cohort included patients from 12 centers in Europe, Asia, and the United States who were on a transplant waiting list from January 1, 2000, to December 31, 2017. The Toronto cohort included patients from 1 transplant center who were on a waiting list from January 1, 2000, to December 31, 2015.

The main outcome was patient death occurring for any reason from the time of waiting list inscription to the last follow-up date, which was December 31, 2019. The data were analyzed from February 1, 2020, to May 31, 2020. The overall median follow-up was 3.3 (interquartile range [IQR],1.5-6.6) years.

Among the 3052 patients in the international cohort, 1011 (33.1%) had a potential living-donor liver transplant (LDLT) and 2041 (66.9%) had a potential deceased-donor liver transplant (DDLT). The median age at first referral was 58 (IQR, 53-63) years, and the group included 2447 men (80.2%). The Toronto cohort included 906 patients (743 men; 82.0%), and the median age at first referral was 59 (IQR, 53-63) years. In the Toronto cohort, 245 participants (27.0%) had a potential LDLT and 661 (73.0%) had a potential DDLT.

In the pre-inverse probability of treatment weighting (IPTW) international cohort, live donor availability was a protective factor for intention-to-treat death (hazard ratio [HR], 0.51; 95% CI, 0.36-0.71; P <.001). The post-IPTW analysis for the international cohort yielded similar results, confirming LDLT as a protective factor (HR, 0.67; 95% CI, 0.53-0.85; P =.001). In the Toronto cohort, the protective factor of live donor availability was confirmed (pre-IPTW: HR, 0.57; 95% CI, 0.45-0.73; P <.001; post-IPTW: HR, 0.52; 95% CI, 0.42-0.65; P <.001).

A living donation was associated with a 33% to 49% reduction in the intention-to-treat death risk according to the HRs in all 4 models. When LDLT was added to the mathematical models, their discriminatory ability further improved.

Study limitations include the retrospective design, and potential initial selection biases that could result in missing confounding factors, possibly favoring outcomes in patients who have an LDLT. In addition, the actual number of patients who died or had tumor progression before listing is not known because of the absence of an available live donor. This was particularly true in centers that performed LDLT exclusively. Finally, several differences were observed between patients in Eastern and Western countries, including HCC pretransplant treatments, genetics, and underlying liver disease.

“Transplant programs worldwide should be encouraged to expand their live donor programs to manage patients with HCC,” commented the investigators.

Disclosure: One of the study authors declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures. 


Lai Q, Sapisochin G, Gorgen A, et al. Evaluation of the intention-to-treat benefit of living donation in patients with hepatocellular carcinoma awaiting a liver transplant. JAMA Surg. Published online July 14, 2021. doi: 10.1001/jamasurg.2021.3112