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Page 2 of 5 Sugawara et al. Hepatoma Res 2018;4:33 I http://dx.doi.org/10.20517/2394-5079.2018.69

and a recurrence-free survival of 83% of the patients who meet these criteria . Many centers worldwide have
[4]
now adopted the criteria for deceased donor liver transplantation and also living donor liver transplantation
(LDLT). However, the criteria have been sometimes estimated as being too strict to include many patients
in the transplant list .
[5]
In Asian countries/regions, unlike the Western countries, LDLT has accounted for the majority of
transplantations . LDLT can be thought to be a private issue among the patients and the families. Therefore
[6,7]
the selection criteria of the patients from the view point of tumor status can be considered on a case-by-case
basis. Also the grafts are not always restricted by the system of the public organ allocation. It should be taken
into account how high the recurrence rate and the chance of survival are and how firm the will to donate
the part of the liver is. Many high-volume transplantation centers have performed LDLT for patients with
HCC based on the criteria extending Milan to include patients with slightly larger tumors as transplant
[8]
candidates and such an expansion of criteria did not result in a significantly higher rate of disease recurrence
after transplantation. The review described the current status of liver transplantation for HCC in Japan and
the other Asian countries/regions.

JAPANESE EXPERIENCE
In Japan, the serious shortage of deceased donor livers has still continued despite the approval of the Japanese
Organ Transplantation Act in 1997 and its revision in 2006. According to a report from the Japanese Liver
Transplantation Society Registry , by the end of 2016, 378 liver transplantations were performed using
[9]
deceased donor grafts while 8825 LDLTs were performed during the same period. Of these, 1598 were
indicated for HCC. The 1-, 3-, 5-, 10-, 15- and 20-year survival rates of LDLT for HCC were 85%, 75%, 70%,
62%, 55%, and 54%, respectively.

The insuring system of the Japanese Ministry of Health, Labor, and Welfare covered the patients who undergo
transplantation only when the tumor status is within the Milan criteria. The tumors should be diagnosed
to be HCC by computed tomography or magnetic resonance imagings obtained within one month before
transplantation. The tumors must be diagnosed on the dynamic computed tomography to be low density in
plain, high in arterial phase, and low in portal phase. Local treatment for HCC must be done at least 3 months
before transplantation is planned. Only the patients with tumors within the Milan criteria can be listed for
and undergo deceased donor liver transplantation. In LDLT, however, many Japanese institutions have their
own criteria beyond the Milan .
[10]
A survey was done using a database consisting of the 653 patients who underwent LDLT for HCC in
[11]
Japan between 1990 and 2005. On the preoperative imagings, 62% were within the Milan criteria while 38%
were beyond. The overall patient survival was 83%, 73%, and 69%. The disease-free survival was 77%, 65%,
and 61%, at 1, 3, and 5 years, respectively. The 5-year recurrence free survival was 90% and 61% for those
within and beyond the Milan, respectively (P < 0.001). HCC recurred in the 92 (14%) recipients, with a rate
at 1, 3, and 5 years of 9%, 20%, and 22%, respectively. The multivariate analysis revealed that preoperative
alpha-feto-protein and des-gamma carboxyprothrombin (DCP) levels were independent factors for HCC
recurrence.

Experience of each center
The Kyoto group proposed that the criteria should be “tumors ≤ 5 cm and the numbers are 10 or less than
[12]
10, and DCP levels < 400 mAU/mL”. One hundred ninety-eight patients underwent LDLT for HCC between
1999 and 2011. Of these, the 147 (76%) patients met the Milan criteria. The 5-year survival rate of those within
the criteria was 82% and that of those beyond was 42% (P < 0.001). The 5-year recurrence rate for those within
the Kyoto criteria was less than that for patients beyond them (4% vs. 51%, P < 0.001).