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Ichida et al. Hepatoma Res 2020;6:54 I http://dx.doi.org/10.20517/2394-5079.2020.59 Page 3 of 11

performed within a month before LT in all cases. Lesions presenting with typical radiological characteristics
of classical HCC, that is, lesions with arterial phase enhancement and low density during the portal phase,
were diagnosed as HCC to be counted and measured. In cases that underwent pretransplant locoregional
treatments, only the size of the viable lesion was measured on the basis of MDCT before LDLT, and on the
basis of pathological findings after LDLT. Essentially, we used the Milan criteria as a standard indication
for LT for HCC; however, we allowed the expanded criteria, i.e., Tokyo criteria, in a private practice setting
as mentioned above. Six cases exceeding the Tokyo criteria exceptionally, underwent LDLT in the early
period. We did not use biomarkers such as AFP and DCP in patient selection.

Donor selection and postoperative management
Until 2015, the estimated graft volume to the recipient standard liver volume (SLV) ratio must be over 40%
for LT at our institution. Since 2016, we have changed the threshold of the graft volume criteria to 35% of
the recipient SLV. The left liver was the first choice for the graft if it satisfied the lower limit. Otherwise,
right liver procurement was indicated if the estimated right liver graft volume was less than 70% of the
donor’s total liver volume, and a right lateral sector graft was used in selected cases. Details of donor
[25]
evaluation and graft selection are described elsewhere . The basic immunosuppression regimen comprised
tacrolimus and steroid for all recipients, and the doses of each drug were gradually tapered over 6 months
after LDLT. Our detailed postoperative recipient management including the immunosuppression protocol
[26]
has been described elsewhere . We do not modify immunosuppression for HCC recipients and do not
use m-TOR inhibitors nor adjuvant chemotherapies. All patients were followed up at our department after
LT according to the following protocol: monthly measurements of AFP and DCP, abdominal ultrasound
performed every 3 months, and contrast-enhanced dynamic MDCT every 6 months. Recurrence was
defined as the emergence of radiological findings in MDCT or magnetic resonance imaging compatible
with typical HCC.

Statistical analysis
Categorical variables were expressed as number (%) and continuous variables were expressed as median
with range. NLR and PLR were calculated by dividing the number of neutrophils or platelets, respectively,
by the number of lymphocytes. Patient overall survival and recurrence rates were calculated using Kaplan-
Meier with Log rank test. A receiver-operating characteristics (ROC) curve analysis and Youden index
were used to define the ideal cut-off values for AFP, AFP-L3, DCP, NLR, and PLR to detect recurrence.
Univariate and multivariate analysis was performed using a Cox proportional hazards model to identify
the predictors of recurrence. Factors with a P value less than 0.05 in a Cox proportional-hazard model
as a univariate analysis were considered potential risk factors and further analyzed in a multivariate Cox
model. The hazard ratio (HR) and 95% confidence interval (CI) were calculated for each variable. Although
seventeen variables listed in the table were examined as potential risk factors, AFP-L3 was excluded from
multivariate analysis because of the quantity of missing data (AFP-L3 was not checked in 19 patients).
Beyond the Milan, 5-5-500, and Japanese DEC were also excluded from multivariate analysis because they
were not considered to be independent factors but composite factors having a strong relation to tumor
number, size, and AFP value. All statistical calculations were performed using JMP Pro 15 (SAS Institute
Inc., Cary, NC, USA). P values less than 0.05 were considered statistically significant.

RESULTS
Patient characteristics
Recipient demographics are summarized in Table 1. There were 116 males and 37 females, with a median
age of 56 (range, 37-67) years. The median model for end-stage liver disease score was 12 (range, 2-34).
Hepatitis C virus positive cases comprised 57% of the cohort. Sixty percent (92/153) had undergone loco-
regional treatments for HCC before LT, including 69 cases with transcatheter arterial chemoembolization,
31 with radiofrequency ablation, 23 with percutaneous ethanol injection therapy, and 14 with surgical