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Page 8 of 19 Kornberg et al. Hepatoma Res 2018;4:60 I http://dx.doi.org/10.20517/2394-5079.2018.86

Table 5. Impact of graft size on outcome in LDLT for HCC
Reference n Impact of GRWR on post-LDLT outcome Impact of GRWR on outcome in advanced HCC
Hu et al. [105] 295 OS was significantly better in GRWR ≤ 0.8% vs. > 0.8% (P =
0.009). RFS tended to be better in GRWR > 0.8 (P = 0.133).
GWRW > 0.8% was identified as independent predictor of
poor OS (HR = 2.166; 95%CI 1.173-4.001; P = 0.013), along
with vascular invasion
Li et al. [106] 597 RFS rates at 1-, 3- and 5 years were 75.9%; 73.3%, and The 1-, 3- and 5-year RFS rates in MC Out patients were 52.4%,
71.7% in GRWR < 0.8%, and 86.4%, 80.8% and 77.9% in 49.3% and 49.3% in GRWR < 0.8%, and 76.5%, 68.3%, and
GRWR ≥ 0.8%, respectively (P = 0.17). The corresponding 64.3% in GRWR ≥ 0.8% (P = 0.049). The corresponding OS
OS rates were 87.8%, 80.3% and 78.7% (GRWR < 0.8%), rates were 77.1%, 65.3%, and 61.5% (GRWR < 0.8%), and 90.2%,
and 93.5%, 87.1%, and 84.1% (GRWR ≥ 0.8%; P = 0.017) 80.1%, and 77.5% (GRWR > 0.8%, P = 0.047). No significant
effect of GRWR on outcome in Milan In patients was found
CI: confidence interval; GRWR: graft-to-recipient body weight ratio; HR: hazard ratio; OS: overall survival; RFS: recurrence-free survival

age ≥ 60 years was reported to be the only independent donor-related predictor of HCC recurrence in a study
[87]
[96]
of 5002 patients of the UNOS database . Comparably, Orci et al. reported on an independent prognostic
effect of donor age > 60 years (HR = 1.38; 95%CI 1.10-1.73; P = 0.006), when analyzing 9742 patients of the
SRTR database. Adequate donor-recipient age matching was shown to improve overall long-term outcome in
[97]
recipients of older donor grafts . However, no data exists on the oncological impact of such a matching policy.

Living donor liver grafts
LDLT has been established as an appropriate alternative approach to fight organ shortage and, thereby, to
decrease risk of drop out from the waiting list, especially in Eastern countries where the number of deceased
donor liver transplants (DDLT) is significantly restricted. Allocation of these organs is not regulated by
public institutions, so that the indication is independent of strict tumor size limitations. Therefore, LDLT
is particularly attractive for advanced HCC patients, who may otherwise not be offered a transplant option
via HCC exceptional MELD allocation, but rather transferred to palliative treatments [98,99] . However, apart
from the donors’ risks related to major hepatectomy, there are important oncological issues that have to be
considered.

Liver grafts from living donors are principally small for size and, thus, exposed to an enhanced acute phase
attack, which is an established promoter of cancer [82,100] . Another important oncological aspect is that fast track
LDLT without HCC MELD-related waiting time may select more aggressive tumors that otherwise would
[101]
have been identified and probably rejected . Based on current mainly retrospective studies of the Eastern
and Western transplant regions, the impact of reduced liver graft size compared to full-size donor livers on
HCC recurrence remains finally unclear. One meta-analysis including 7 studies and 1310 patients did not find
[102]
significant outcome differences between both transplant procedures, also when stratified according to MC .
In contrast, a more recent meta-analysis by Grant et al. [103] including 633 LDLT and 1232 DDLT patients
provided evidence for reduced RFS following LDLT. Prospective multicenter studies are need, implementing
standardized tumor selection criteria, comparable neoadjuvant tumor treatments and intent-to-treat outcome
data, which seems to be illusionary with regard to different strategies and mentalities between Eastern and
Western countries.

What seems to be equally important is, whether LDLT is principally able to produce acceptable outcome in
beyond Milan patients, which by definition may also be lower than those for Milan In patients. Regarding
this, it became apparent in recent years that post-LDLT 5-year RFS rates far beyond 50% are possible in MC
Out patients when implementing parameters of biological tumor aggressiveness, such as AFP, PIVKA II or
PET-status [98,104] . Apart from that, size of the living related donor graft may be another important prognostic
[105]
factor that should be considered [Table 5]. In a series of 295 HCC patients following LDLT, Hu et al.