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Table 4. Impact of donor age on HCC recurrence
Reference n Impact on post-LT HCC recurrence
Sharma et al. [95] 94 Median donor age was 49 y and 36 y in patients with and without HCC relapse (P = 0.008). Along
with number and largest diameter of tumor nodules, donor age was identified as the only pre-LT
available independent risk factor of tumor recurrence (HR = 1.06; 95%CI 1.02-1.10; P = 0.002)
Vagefi et al. [96] 5002 (UNOS database) Cumulative incidence of HCC recurrence at 1-, 2-, 3-, and 4-year post-LT was 3%, 5.1% 6.4% and
7.3% in donors < 60 y, but 4.5%, 8.3%, 10.4% and 11.8% in donors > 60 y (P < 0.05). Apart from
non-local organ sharing, donor age ≥ 60 years was reported to be the only independent donor-
related predictor of HCC recurrence (HR = 1.42; 95%CI 1.09-1.84; P = 0.009)
Orci et al. [87] 9724 (SRTR database) Donor age > 60 y (HR = 1.38; 95%CI 1.10-1.73; P = 0.006) was identified as an independent
promoter of HCC relapse
CI: confidence interval; HCC: hepatocellular carcinoma; HR: hazard ratio; LT: liver transplantation

In another study including 9724 liver transplant recipients of the Scientific Registry of Transplant Recipients
(SRTR) database, WIT ≥ 19 min was associated with increased risk of HCC relapse in uni- and multivariable
[87]
analysis. However, the authors did not stratify data according to MC .
Marginal liver grafts
The dramatic shortage of appropriate donor livers enhances the risk of patients’ drop-out due to tumor
progression and/or morbidity or mortality related to cirrhosis progression during waiting times. Therefore,
the so-called extended criteria donor grafts (ECD) are increasingly used for decreasing the fatal discrepancy
[88]
between demand and donor organ availabilities . In order to avoid penalizing patients with standard criteria
HCC or other indications, marginal liver grafts, such as steatotic livers, living donor liver grafts, donor
livers after cardiac death (DCD) and older donor grafts are currently accepted for patients with advanced
HCC stages, not at least as these patients frequently present with compensated liver function. However, such
ECD livers are more susceptible to severe I/R damage, which may impair immunological and oncological
[89]
outcome .

Steatotic donor livers
In recent years, liver steatosis has become a serious medical issue due to growing rates of diabetes, obesity,
metabolic syndrome and alcohol abuse. Consequently, the numbers of explanted, offered and finally accepted
steatotic liver grafts has significantly increased in recent years. However, donor graft steatosis is associated with
[90]
overall poorer outcome post-LT . Based on histopathologic assessment, we distinguish between mild (< 30%),
moderate (30%-60%) and severe (> 60%) liver steatosis, whereby particularly recipients of the latter are subject
[91]
to an extraordinary risk of hepatic I/R damage with risk of post-LT allograft failure . In an experimental
[92]
setting, Orci et al. have shown that I/R injury contributes to more severe intrahepatic and remote HCC
[93]
recurrence with enhanced liver steatosis. Although statistical significance was lacking, Teng et al. reported
on a clear trend of higher HCC recurrence rates in recipients of moderate-to-severe steatotic (50%) compared to
[87]
non-steatotic grafts (28.7%) and mild steatosis (20.8%). In a large registry trial (n = 3007), Orci et al. reported
that graft steatosis > 60% was an independent promoter of HCC recurrence post-LT (HR = 1.65; 95%CI 1.03-2.64;
P = 0.037).

Donor age
The use of elderly donor livers increases the risk of early post-LT graft loss, arterial and biliary complications,
and immunological insults. Particularly presence of hepatitis C and prolonged ischemia times are known
[94]
triggers of the negative impact of older donor grafts . In recent years, there is growing evidence that donor
age may also affect oncological outcome in HCC LT patients [Table 4]. In a retrospective study of 94 liver
[95]
recipients, Sharma et al. were the first to identify donor age as an independent predictor of HCC recurrence,
along with number of tumor lesions and size of the largest tumor diameter. Two large registry studies have
subsequently confirmed the oncological importance of donor age. Apart from non-local organ sharing, donor