Living Donor Liver Transplantation for
Hepatocellular Carcinoma: To Expand
(Beyond Milan) or Downstage (to
SEE ARTICLE ON PAGE 369
For patients with hepatocellular carcinoma (HCC)
exceeding the Milan criteria, survival after liver trans-
plantation (LT) incrementally decreases with increas-
ing tumor size and number.
The allocation system
for deceased donors in the United States is largely
restricted to HCC within Milan criteria and does not
accommodate to even modest expansion of tumor
Wait-list dropout rates remain substantial even
for HCC within Milan criteria in long wait-time
Living donor liver transplantation (LDLT)
has been performed for patients with HCC beyond
Milan criteria adhering to the principle that the risk to
the donor is justiﬁed by the expectation of an accept-
able outcome for the recipient (double equipoise).
However, the boundaries of tumor size and number to
be considered for LDLT have varied widely among
centers without a consensus based on reproducible
Furthermore, the minimal acceptable survival
threshold after LDLT has not been well deﬁned.
In this issue of Liver Transplantation, Llovet et al.
from the Barcelona Clinic Liver Cancer (BCLC)
group report their longterm results up to 10 years fol-
lowing LDLT for HCC beyond Milan criteria in a
prospectively applied protocol.
The study cohort met
the proposed BCLC extended criteria (1 tumor > 5cm
but 7 cm, 2-3 tumors at least 1 tumor > 3cm
but 5 cm, or 4-5 tumors 3 cm) and other protocol
eligibility requirements including Eastern Cooperative
Oncology Group performance status 0 and Child-
Pugh class A/B. Out of 22 patients enrolled between
2001 and 2014, 5 were successfully downstaged with
local-regional therapy (LRT) from beyond BCLC
extended criteria to within Milan criteria. A total of 12
of the 22 patients received LRT, in whom 10 were
downstaged to within Milan criteria prior to LDLT.
This study was therefore composed of a heterogeneous
group of patients who underwent LDLT either with
extended criteria or after tumor downstaging—2 dif-
ferent approaches that should be considered separately.
Explant tumor stage exceeded BCLC extended cri-
teria in 50% (understaged) and within Milan criteria in
18% (downstaged). Poorly differentiated tumor grade
and microvascular invasion were observed in 23% and
46%, respectively. Despite the frequency of unfavorable
histopathologic characteristics, 5- and 10-year survival
rates after LDLT were excellent at 80% and 67%,
respectively. The cumulative probability of HCC
recurrence was 24% and 44% at 5 and 10 years, respec-
tively. In all but 1 case, HCC recurrence occurred
beyond 4 years after LDLT. The reason for the sur-
prising predominance of late HCC recurrence is
unknown. All 7 (32%) patients with HCC recurrence
had recurrent hepatitis C after LDLT, including 5
with graft cirrhosis. Some of these cases might there-
fore represent de novo HCC development in a graft
with advanced ﬁbrosis rather than recurrent tumor.
An intriguing question raised in the BCLC study is
whether downstaging is preferable to expansion of
criteria in LDLT. The proposed BCLC extended cri-
teria are very similar to the University of California,
San Francisco downstaging criteria, which also include
an upper limit in the total tumor diameter
Abbreviations: AFP, alpha-fetoprotein; BCLC, Barcelona Clinic
Liver Cancer; DCP, des-gamma-carboxyprothrombin; HCC, hepato-
cellular carcinoma; LDLT, living donor liver transplantation; LRT,
local-regional therapy; LT, liver transplantation.
Address reprint requests to Neil Mehta, M.D., Division of Gastroen-
terology, Department of Medicine, University of California, San
Francisco, 513 Parnassus Avenue, Room S-357, San Francisco, CA
94143-0538. Telephone: 415-476-2777; FAX: 415-476-0659;
Received January 16, 2018; accepted January 16, 2018.
2018 by the American Association for the Study of Liver
View this article online at wileyonlinelibrary.com.
Potential conflict of interest: Nothing to report.