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reported on significantly better 1- and 3- year OS rates in graft-to-recipient body weight ratio (GRWR) ≤ 0.8%
vs. > 0.8% (P = 0.009), whereas the corresponding RFS rates tended to be different (P = 0.133). Besides vascular
invasion, GRWR was identified as the only independent and significant prognostic factor for OS. Analyzing
[106]
597 consecutive LDLT patients, Lee et al. were able to demonstrate that RFS in Milan Out patients was
significantly better in GRWR < 0.8% (P = 0.049) [Table 5].

DCD
In order to cope with dramatic donor organ shortage, donors after cardiac or circulatory death have been
increasingly used in recent years. In comparison to LT using donors after brain death (DBD), DCD LT is
characterized by repeat and prolonged WIT, higher susceptibility to I/R damage, increased rate of post-
LT graft failure, higher rates of re-transplants, and impaired overall outcome [107,108] . The impact of applying
DCD liver grafts on the oncological outcome is currently assessed controversially. Using the SRTR database,
[109]
Croome et al. demonstrated inferior survival after DCD LT (55.86% at 5-year post-LT) compared to DBD
LT (63.77% at 5-years post-LT; P < 0.001) in HCC patients, without including data on tumor recurrence. More
recently, several large single-center studies did not find a significant difference in cancer-related outcome
[87]
between both transplant procedures [110,111] . Using the SRTR database, Oric et al. failed to identify a negative
prognostic impact of DCD grafts when being compared to DBD livers. However, WIT exceeding 19 min
proved to be an independent predictor of HCC relapse in the subset of DCD liver recipients (HR = 4.26;
95%CI 1.2-15.1, P = 0.025).

Improving cancer-specific outcome by mitigating I/R injury
Several approaches to improve tumor-specific outcome by reducing hepatic I/R injury are currently under
experimental and clinical consideration.

Orci et al. [112] demonstrated that ischemic preconditioning prior to I/R injury reduced tumor load in an
experimental setting of rat liver steatosis to an equal level as in non-steatotic control grafts. The same group
recently demonstrated in another experimental study that remote ischemic preconditioning may reduce I/R
[113]
injury and modulate the gut-liver axis, finally alleviating HCC recurrence .
In a retrospective clinical analysis, our transplant group was able to demonstrate that early post-LT treatment
with prostaglandin E1 (PGE1) reduces hepatic I/R damage and provides beneficial immunomodulatory
[114]
capabilities, finally improving cancer-specific outcome . In a series of 106 HCC LT patients, RFS rates at
3- and 5-year post LT were significantly better in the PGE1-treatment group (87.9%; 85.7%) compared to the
non-PGE1 subset (65.3%; 63.1%; P = 0.003). In addition, rate of early HCC relapse within 1 year from LT was
significantly higher without PGE1 treatment (34% vs. 5.1%; P < 0.001). When stratified according the MC,
PGE1-therapy did not exert an independent prognostic impact in Milan In, whereas it was identified as a
significant and independent promoter of RFS in patients with MC Out patients (HR = 5.09; 95%CI 1.64-15.76;
[114]
P = 0.005) .

The increasing use of different hypo- or normothermic extracorporeal liver perfusion systems may be another
promising approach to expand the pool of transplantable ECD livers. Pre-transplant assessment of organ
viability and reducing susceptibility to hepatic I/R are the suggested scope of application. In fact, the safety
and feasibility of ex-situ machine preservation have already been demonstrated. First clinical trials suggested
reduced morbidity and mortality in recipients of high risk organs that were pretreated with extracorporeal
[118]
machine perfusion devices [115-117] . Just recently, He et al. from Guangzhou transplant center presented the
first case of “ischemia-free transplantation” of a severely steatotic graft by using normothermic machine
perfusion without stopping blood supply, already initiated during donor liver harvesting. So far, there are no