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Cullen et al. Hepatoma Res 2020;6:76 I http://dx.doi.org/10.20517/2394-5079.2020.69 Page 3 of 14

The available literature comparing outcomes of LDLT and DDLT for HCC is limited [14-16] . Early reports
showed recurrence rates were higher after LDLT than DDLT, but this has been contradicted by recent
work [17,18] . An important advantage of LDLT is that it effectively allows HCC patients to not be in direct
competition with liver failure patients whose Model for End-Stage Liver Disease score afford them higher
[16]
wait list priority. Goldaracena et al. found patients undergoing LDLT had faster access to transplant and
shorter wait times compared with DDLT. In this recent intention-to-treat analysis of 219 LDLTs and 632
DDLTs for HCC, patients with a potential live donor had a 33% reduction in risk of death from the time of
listing due to shorter wait time and decreased waitlist dropout risk. LDLT actually offered a survival benefit
over DDLT in this analysis.

Another important aspect unique to LDLT is that each graft is a private gift and not subject to the
allocation system. Donation can be direct or altruistic. Patients with advanced HCC should be evaluated
on an individual basis so that those outside conventional criteria who would benefit from a transplant can
receive one without the risks of disease progression while on the waitlist and its concomitant mortality.

CONVENTIONAL CRITERIA FOR LIVER TRANSPLANT FOR HEPATOCELLULAR CARCINOMA
The Milan criteria established the benchmark for acceptable outcomes for liver transplantation in HCC.
[19]
Mazzaferro et al. reported recurrence rates less than 15% and a 5-year survival of 75% when transplanting
HCC patients with (a) one tumor less than 5 cm or (b) three tumors each less than 3 cm. The University
of California at San Francisco (UCSF) liberalized these size limitations and selected patients with (a) one
solitary tumor up to 6.5 cm or (b) three tumors with the largest 4.5 cm or less and total tumor diameter
[20]
8 cm or less . Using these expanded criteria, the UCSF group matched Milan outcomes with recurrence
and 5-year survival rates of 10% and 75.2%, respectively. In 2008, the Asan Medical Center group in Seoul,
South Korea, further expanded eligibility criteria to include patients with up to 5 tumors and size less than
[21]
6 cm and achieved a 5-year survival rate of 81.6% .
TRANSPLANTATION BEYOND CONVENTIONAL CRITERIA
Many centers have sought to expand these traditional criteria, specifically by emphasizing tumor biology
[22]
and behavior as opposed to a reliance on tumor size and number . The extended Toronto Criteria places
no restrictions on number of tumors or tumor size and offers transplantation to patients without systemic
[5]
cancer-related symptoms, extrahepatic disease, vascular invasion, or poorly differentiated tumors .
Sapisochin et al. further validated these criteria with a prospective study including 105 patients outside
[5]
Milan and 76 beyond UCSF criteria, and reported a 5-year survival of 69% which did not differ significantly
from patients within Milan. An important aspect of this study was the authors found an alpha-fetoprotein
(AFP) level greater than 500 ng/mL to be predictive of poor outcomes.

In Asia, LDLT predominates over DDLT, and this region has been an epicenter for criteria expansion.
In 2016, the National Cancer Center - Korea reported an 85.2% overall 5-year survival and 84%
disease free survival after LDLT for 164 patients with total tumor size of 10 cm or less and a negative
18F-fluorodeoxyglucose positron emission tomography scan . The Kyushu Criteria, published in 2017,
[23]
demonstrated a 75.9% 5-year survival rate when performing LDLT for 161 patients with any number of
[24]
tumors, but with size less than 5 cm or des-gamma carboxy prothrombin levels less than 300 mAU/mL .
An interesting aspect of this study was that it showed LDLT had a survival benefit when compared with
DDLT in an intention to treat sub-analysis, despite LDLT patients having more advanced tumor stage.

LIVING DONOR LIVER TRANSPLANTATION FOR ADVANCED HEPATOCELLULAR
CARCINOMA
Because deceased donor organs are allocated to patients on the waiting list expected to survive the longest
after transplant, advanced HCC often precludes DDLT. Many patients outside transplantable criteria are